This document summarizes molecularly imprinted polymers (MIPs), which are synthetic polymers that exhibit high selectivity for target molecules. It discusses two main approaches for creating MIPs - covalent and non-covalent imprinting - and notes that non-covalent imprinting is more commonly used due to its simplicity. The document also describes factors that influence molecular recognition in MIPs, such as functional group complementarity and interactions like hydrogen bonding. Additionally, it discusses considerations for optimizing the polymer structure and selection of the template molecule to improve molecular imprinting performance.
Network polymers derived from the integration of flexible organic polymers an...Berkay AKKOÇ
Network polymers derived from the integration of flexible organic polymers and rigid metal organic frameworks. My class notes about a kind of inorganic polymer. Review.
Affinity chromatography is a technique that separates proteins based on a reversible interaction between a protein and a ligand coupled to a chromatography matrix. It offers high selectivity and purification. The document discusses the definition, principles, components, steps, applications, advantages and disadvantages of affinity chromatography. Key terms like matrix, spacer arm, ligand, binding, elution and wash are explained. Common applications include immunoglobulin purification, recombinant tagged proteins, and separation of enzyme substrates. Advantages are high specificity and yield, while disadvantages include time consumption and solvent use.
This document discusses two methods for synthesizing bottlebrush polymers: grafting-from and transfer-to. Bottlebrush polymers have rigid, nanoscopic structures that give them unique mechanical and rheological properties. The transfer-to approach combines grafting-from and grafting-to by allowing polymeric radicals to detach from the backbone and reattach through a chain transfer reaction, allowing for lower dispersities and higher conversions than traditional grafting-from. The document aims to compare the transfer-to and grafting-from methods using size exclusion chromatography and nuclear magnetic resonance spectroscopy to highlight the differences between the two techniques.
1) Bottlebrush polymers are becoming more relevant due to their unique structures and properties. They differ from linear polymers in that they have polymeric side chains grafted along a backbone.
2) There are four main approaches to synthesizing bottlebrush polymers: grafting-from, grafting-to, grafting-through, and transfer-to. The transfer-to approach allows for lower dispersities and higher conversions compared to typical grafting-from methods.
3) The research is investigating the transfer-to approach for bottlebrush polymerization and comparing it to grafting-from. A chain transfer agent was designed and tested for the transfer-to method.
Separation of Enantiomers using polymer membraneslavanyak49
The document discusses the separation of enantiomers using polymer membranes. It explains that enantiomers are non-superimposable mirror images that have the same physical properties but different biological effects. Polymer membranes use chiral recognition sites to preferentially transport one enantiomer over the other. There are two main mechanisms: diffusion-selective membranes use intrinsically chiral polymers while sorption-selective membranes embed chiral selectors into the membrane. The literature review covers studies on enantioselective permeation through polymeric membranes. The objective is to understand the resolution mechanism and study permeability/selectivity using computational methods.
Isolation purification technique for Therapeutic Bio molecules : Protein-PeptideRohit Gurav
The document discusses isolation and purification techniques of therapeutic biomolecules. It describes how proteins and peptides can be isolated from animal sources like pancreas, brains, and salmon. Magnetic separation techniques like magnetic-activated cell sorting (MACS) can be used to isolate target proteins and peptides. The document also discusses various methods used for sample disruption like grinding, shearing, beating and shocking. Key techniques for purification of isolated biomolecules include ion exchange chromatography, size exclusion chromatography, ammonium sulfate precipitation, and high pressure liquid chromatography.
This document discusses mucoadhesive drug delivery systems, which use bioadhesive polymers that adhere to mucosal membranes to increase drug residence time and bioavailability. It covers the basics of mucosal membranes and theories of mucoadhesion, as well as the mechanisms, types of polymers, formulations, and targets for bioadhesive drug delivery. The goal of these systems is to deliver drugs through mucosal routes and potentially bypass first-pass metabolism through prolonged adhesion to the site of administration.
Affinity chromatography is a separation technique that uses the specific binding interaction between an immobilized ligand and its binding partner. It relies on a solid support with an affinity ligand that selectively binds the target molecule. The target molecule is purified in a single step by binding to the ligand, washing away unbound molecules, and then eluting the target molecule under different conditions. Affinity chromatography provides high selectivity and purity and is widely used to purify proteins and other biomolecules.
Network polymers derived from the integration of flexible organic polymers an...Berkay AKKOÇ
Network polymers derived from the integration of flexible organic polymers and rigid metal organic frameworks. My class notes about a kind of inorganic polymer. Review.
Affinity chromatography is a technique that separates proteins based on a reversible interaction between a protein and a ligand coupled to a chromatography matrix. It offers high selectivity and purification. The document discusses the definition, principles, components, steps, applications, advantages and disadvantages of affinity chromatography. Key terms like matrix, spacer arm, ligand, binding, elution and wash are explained. Common applications include immunoglobulin purification, recombinant tagged proteins, and separation of enzyme substrates. Advantages are high specificity and yield, while disadvantages include time consumption and solvent use.
This document discusses two methods for synthesizing bottlebrush polymers: grafting-from and transfer-to. Bottlebrush polymers have rigid, nanoscopic structures that give them unique mechanical and rheological properties. The transfer-to approach combines grafting-from and grafting-to by allowing polymeric radicals to detach from the backbone and reattach through a chain transfer reaction, allowing for lower dispersities and higher conversions than traditional grafting-from. The document aims to compare the transfer-to and grafting-from methods using size exclusion chromatography and nuclear magnetic resonance spectroscopy to highlight the differences between the two techniques.
1) Bottlebrush polymers are becoming more relevant due to their unique structures and properties. They differ from linear polymers in that they have polymeric side chains grafted along a backbone.
2) There are four main approaches to synthesizing bottlebrush polymers: grafting-from, grafting-to, grafting-through, and transfer-to. The transfer-to approach allows for lower dispersities and higher conversions compared to typical grafting-from methods.
3) The research is investigating the transfer-to approach for bottlebrush polymerization and comparing it to grafting-from. A chain transfer agent was designed and tested for the transfer-to method.
Separation of Enantiomers using polymer membraneslavanyak49
The document discusses the separation of enantiomers using polymer membranes. It explains that enantiomers are non-superimposable mirror images that have the same physical properties but different biological effects. Polymer membranes use chiral recognition sites to preferentially transport one enantiomer over the other. There are two main mechanisms: diffusion-selective membranes use intrinsically chiral polymers while sorption-selective membranes embed chiral selectors into the membrane. The literature review covers studies on enantioselective permeation through polymeric membranes. The objective is to understand the resolution mechanism and study permeability/selectivity using computational methods.
Isolation purification technique for Therapeutic Bio molecules : Protein-PeptideRohit Gurav
The document discusses isolation and purification techniques of therapeutic biomolecules. It describes how proteins and peptides can be isolated from animal sources like pancreas, brains, and salmon. Magnetic separation techniques like magnetic-activated cell sorting (MACS) can be used to isolate target proteins and peptides. The document also discusses various methods used for sample disruption like grinding, shearing, beating and shocking. Key techniques for purification of isolated biomolecules include ion exchange chromatography, size exclusion chromatography, ammonium sulfate precipitation, and high pressure liquid chromatography.
This document discusses mucoadhesive drug delivery systems, which use bioadhesive polymers that adhere to mucosal membranes to increase drug residence time and bioavailability. It covers the basics of mucosal membranes and theories of mucoadhesion, as well as the mechanisms, types of polymers, formulations, and targets for bioadhesive drug delivery. The goal of these systems is to deliver drugs through mucosal routes and potentially bypass first-pass metabolism through prolonged adhesion to the site of administration.
Affinity chromatography is a separation technique that uses the specific binding interaction between an immobilized ligand and its binding partner. It relies on a solid support with an affinity ligand that selectively binds the target molecule. The target molecule is purified in a single step by binding to the ligand, washing away unbound molecules, and then eluting the target molecule under different conditions. Affinity chromatography provides high selectivity and purity and is widely used to purify proteins and other biomolecules.
Novel drug delivery systems aim to optimize drug pharmacokinetics, reduce toxicity, and increase efficacy and bioavailability. They include polymers, micro/nanoparticles, liposomes, micelles, and hydrogels that can encapsulate, protect, target, and gradually release drugs. These systems help minimize harmful side effects, maximize drug accumulation at target sites, and overcome biological barriers to treatment of severe diseases.
The document summarizes strategies for protein purification. It discusses that protein purification separates and isolates proteins from complex mixtures using differences in their physical and chemical properties. It outlines various centrifugation and chromatography techniques used in protein purification, including differential centrifugation, gel filtration, ion exchange chromatography, and affinity chromatography. These techniques separate proteins based on properties like size, charge, and binding affinity. The document also notes that protein purification is now performed from research to industrial scales and that affinity tagging has revolutionized the field.
This document discusses separation of enantiomers using polymer membranes. It notes that enantiomers often have different biological properties and one may be active while the other causes side effects. Polymer membranes can separate enantiomers using chiral recognition sites. Common polymers used include poly(γ-methyl-L-glutamate) and cyclodextrins immobilized in the membrane. The document also discusses mechanisms of separation and examples of separating amino acids and drugs using membranes.
This document provides an overview of a final year project that compares protein loading and delivery between mesostructured and non-porous bioceramics. The project involves synthesizing different bioceramics, loading proteins like lysozyme and bovine serum albumin at various concentrations, and characterizing the loading efficiencies. Initial results found that higher protein concentrations and mesostructured bioceramics had higher loading efficiencies for lysozyme, while lower concentrations had higher efficiencies for bovine serum albumin. Future work is proposed to study protein delivery and explore additional factors that influence loading.
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...iosrphr_editor
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research paper publishing, where to publish research paper, journal publishing, how to publish research paper, Call for research paper, international journal, publishing a paper, call for paper 2012, journal of pharmacy, how to get a research paper published, publishing a paper, publishing of journal, research and review articles, Pharmacy journal, International Journal of Pharmacy, hard copy of journal, hard copy of certificates, online Submission, where to publish research paper, journal publishing, international journal, publishing a paper
Untargeted metabolomics, namely discovery metabolomics, involves the comparison of the metabolome between the control and test groups, to identify differences between their metabolite profiles which may be relevant to specific biological conditions.
This document discusses polymer-matrix nanocomposites, which consist of a polymeric matrix with nanoscale particles dispersed within. Nanoparticles can control the fundamental properties of materials without changing their chemical composition. Polymer nanocomposites are classified as thermoplastic, thermoset, or elastomer based. They are prepared through methods like solution casting or melt blending. Polymer nanocomposites demonstrate improved electrical, optical, mechanical and barrier properties compared to conventional composites. Applications include the automobile sector, energy storage, coatings, and products requiring low flammability.
This document provides an overview of pharmacophore mapping and pharmacophore-based screening. It defines a pharmacophore as the pattern of molecular features responsible for a drug's biological activity. The key steps in pharmacophore modeling are identifying common binding elements in active compounds, generating potential ligand conformations, and determining the 3D relationships between pharmacophore elements. Pharmacophore models can be generated manually based on known active ligands or automatically using software. Receptor-based pharmacophore generation uses the 3D structure of the target protein to identify favorable binding sites. Overall, pharmacophore mapping is used in computer-aided drug design to identify novel ligands that interact with the same biological target.
A composite is a material made from two or more constituent materials with distinct properties. Nanocomposites contain one phase with nanoscale features like nanoparticles, nanotubes, or lamellar structures. Good interaction between the nanoparticles and matrix and good dispersion of particles in the matrix improve composite properties. Nanocomposites can be classified based on dimensionality of the nanomaterial or synthesis method and have applications like flame retardancy, high mechanical properties, and gas barrier performance. They are characterized using techniques like TEM, SEM, AFM, and XRD. Polymer/clay nanocomposites are an important type where clay layers exfoliate or intercalate in the polymer matrix.
This document discusses various chromatography techniques used to purify biomolecules, including affinity chromatography, ion exchange chromatography, size exclusion chromatography, and reversed phase chromatography. It provides details on how each technique separates molecules based on specific properties, such as biological recognition (affinity chromatography), charge (ion exchange chromatography), size (size exclusion chromatography), and hydrophobicity (reversed phase chromatography).
Introduction
Proteins
Function Of Protein And Their Properties
Protein Isolation And Purification
Methods Of Cell Lysis
Steps Of Protein Characterisation:
Determination Of Protein Concentration
Biuret Reaction
Lowry (Folin-Lowry) Method
UV- Spectroscopy
Assessment Of Protein Purity
SDS -Phage
Immunoblot
Surface Charge Analysis
Isoelectro Focusing
Ion Exchange Chromatography
Size, Shape And Conformation Analysis
2d-Electrophorasis
X-Ray Crytalliography
Protein Structure and Sequence Analysis
Edman Sequencing
Conclusion
References
This document discusses bioadhesive drug delivery systems. It begins by defining bioadhesion as the interfacial molecular forces that allow polymers to adhere to biological surfaces for extended periods of time. It then discusses various bioadhesive polymers, both natural and synthetic, that are commonly used in drug delivery formulations. These include polymers like acacia gum, alginic acid, carbomers, and hyaluronic acid. The document also outlines the three main mechanisms by which bioadhesion occurs: wetting and swelling of polymers, interpenetration of polymer chains with mucosal membranes, and formation of chemical bonds between entangled chains. Finally, it provides examples of different types of bioadhesive drug delivery formulations that can
This PhD thesis examines various biodegradable materials as alternatives to petroleum-based plastics. It studies nanocomposites made from polylactic acid and a PLA-PBAT blend reinforced with nanoclays and silica. The effects on mechanical properties, thermal stability, and degradation behavior are analyzed. A second part studies biocomposites of natural fibers like wood and flax in a biodegradable polymer matrix. The fiber type, adhesion, water absorption, and creep behavior under stress and temperature conditions are evaluated to understand material performance. The aim is to develop fully biodegradable composite materials with enhanced and controllable properties.
Affinity chromatography and gel filterationAshfaq Ahmad
Affinity chromatography is a technique that uses the specific binding properties of a molecule to purify it from a mixed sample. The process involves passing a sample over a column containing beads with affinity ligands attached. Proteins in the sample either bind tightly, bind loosely, or do not bind to the ligands on the beads. Multiple wash steps are used to remove non-binding and loosely binding proteins, leaving only the tightly bound protein of interest, which can then be eluted and collected in a purified form.
In silico discovery of histone methyltranferase 1juancarlosrise
This study investigated potential inhibitors of the histone methyltransferase SETD2 using in silico methods. Two pharmacophore models were generated and used to screen a database of 150,000 compounds, filtering it to 31,669 potential leads. Molecular docking ranked these by predicted binding energy, identifying 58 compounds with binding energies from -9.7 to -9.0 kcal/mol. Further refinement of the models and testing of top-scoring compounds may reveal inhibitors of histone methylation and cancer progression.
This document discusses nanoparticles, including their definition as submicron colloidal structures composed of polymers that are 10-1000nm in size. Nanoparticles can be nanospheres or nanocapsules and are useful for site-specific drug delivery. Some key advantages are achieving maximum drug effects with minimal side effects through active and passive targeting. The document outlines various polymer types used in nanoparticle production and evaluation methods like particle size, surface charge, drug loading efficiency and in vitro drug release.
Atomic force spectroscopy, a technique derived from Atomic Force Microscopy (AFM), allowed us to distinguish nonspecific and specific interactions between the acetolactate synthase enzyme (ALS) and anti-atrazine antibody biomolecules and the herbicides imazaquin, metsulfuron-methyl and atrazine. The presence of specific interactions increased the adhesion force (Fadh) between the AFM tip and the herbicides, which made the modified tip a powerful biosensor. Increases of approximately 132% and 145% in the Fadh values were observed when a tip functionalized with ALS was used to detect imazaquin and metsulfuron-methyl, respectively. The presence of specific interactions between the atrazine and the anti-atrazine antibody also caused an increase in the Fadh values (approximately 175%) compared to those observed when using an unfunctionalized tip. The molecular modeling results obtained with the ALS enzyme suggest that the orientation of the biomolecule on the tip surface could be suitable for allowing interaction with the herbicides imazaquin and metsulfuron-methyl
This document summarizes several common techniques used to purify and characterize proteins:
1. Proteins are first isolated from cells through homogenization and then separated from contaminants using techniques like salting out with ammonium sulfate or differential centrifugation.
2. Column chromatography techniques like size-exclusion chromatography, affinity chromatography, and ion exchange chromatography are used to further purify proteins based on properties like size, specific binding interactions, or charge.
3. Electrophoresis, isoelectric focusing, and techniques like amino acid analysis, Edman degradation, and enzymatic or chemical cleavage are then used to determine a protein's primary structure by separating peptide fragments and determining their sequence.
This document discusses various NMR techniques for ligand screening in drug discovery. It begins by providing background on the increasing role of NMR in drug research due to its ability to sensitively detect molecular interactions and provide structural information. The document then reviews both ligand-observed and target-observed NMR screening techniques, describing methods based on changes in molecular diffusion, relaxation, and intramolecular or intermolecular magnetization transfer upon ligand binding. Specific techniques discussed include saturation transfer difference (STD) NMR, transferred nuclear Overhauser effect (trNOE), and NOE pumping. The review concludes by noting the dual importance of NMR for drug screening and structure-based drug design.
Analytical techniques for separation or purification of proteinsrohini sane
A comprehensive presentation on Analytical techniques for separation or purification of proteins for MBBS , BDS, B Pharm & Biotechnology students to facilitate self- study.
Delivery of drugs in therapeutic concentration, to target receptor, is achieved by suitable polymers. Thus, generally it is not possible to target the drug by using a single polymer. Now a days polymer grafting plays a major role in targeted drug delivery system. Grafting may be done by different techniques. These grafted polymers are suitable for site specific drug delivery system. In can minimize the disadvantages of natural polymer and also synthetic polymer with goodness of both.
This document discusses molecular docking and different models used to describe molecular recognition between biomolecules. It begins by defining molecular recognition and docking, and describes early models like the lock-and-key and induced-fit models. It then discusses computational docking methods, including representing molecules, scoring docked poses, and search algorithms to generate poses. Flexibility is an important consideration, and methods to incorporate flexibility of both small molecule ligands and protein receptors are described.
Novel drug delivery systems aim to optimize drug pharmacokinetics, reduce toxicity, and increase efficacy and bioavailability. They include polymers, micro/nanoparticles, liposomes, micelles, and hydrogels that can encapsulate, protect, target, and gradually release drugs. These systems help minimize harmful side effects, maximize drug accumulation at target sites, and overcome biological barriers to treatment of severe diseases.
The document summarizes strategies for protein purification. It discusses that protein purification separates and isolates proteins from complex mixtures using differences in their physical and chemical properties. It outlines various centrifugation and chromatography techniques used in protein purification, including differential centrifugation, gel filtration, ion exchange chromatography, and affinity chromatography. These techniques separate proteins based on properties like size, charge, and binding affinity. The document also notes that protein purification is now performed from research to industrial scales and that affinity tagging has revolutionized the field.
This document discusses separation of enantiomers using polymer membranes. It notes that enantiomers often have different biological properties and one may be active while the other causes side effects. Polymer membranes can separate enantiomers using chiral recognition sites. Common polymers used include poly(γ-methyl-L-glutamate) and cyclodextrins immobilized in the membrane. The document also discusses mechanisms of separation and examples of separating amino acids and drugs using membranes.
This document provides an overview of a final year project that compares protein loading and delivery between mesostructured and non-porous bioceramics. The project involves synthesizing different bioceramics, loading proteins like lysozyme and bovine serum albumin at various concentrations, and characterizing the loading efficiencies. Initial results found that higher protein concentrations and mesostructured bioceramics had higher loading efficiencies for lysozyme, while lower concentrations had higher efficiencies for bovine serum albumin. Future work is proposed to study protein delivery and explore additional factors that influence loading.
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...iosrphr_editor
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research paper publishing, where to publish research paper, journal publishing, how to publish research paper, Call for research paper, international journal, publishing a paper, call for paper 2012, journal of pharmacy, how to get a research paper published, publishing a paper, publishing of journal, research and review articles, Pharmacy journal, International Journal of Pharmacy, hard copy of journal, hard copy of certificates, online Submission, where to publish research paper, journal publishing, international journal, publishing a paper
Untargeted metabolomics, namely discovery metabolomics, involves the comparison of the metabolome between the control and test groups, to identify differences between their metabolite profiles which may be relevant to specific biological conditions.
This document discusses polymer-matrix nanocomposites, which consist of a polymeric matrix with nanoscale particles dispersed within. Nanoparticles can control the fundamental properties of materials without changing their chemical composition. Polymer nanocomposites are classified as thermoplastic, thermoset, or elastomer based. They are prepared through methods like solution casting or melt blending. Polymer nanocomposites demonstrate improved electrical, optical, mechanical and barrier properties compared to conventional composites. Applications include the automobile sector, energy storage, coatings, and products requiring low flammability.
This document provides an overview of pharmacophore mapping and pharmacophore-based screening. It defines a pharmacophore as the pattern of molecular features responsible for a drug's biological activity. The key steps in pharmacophore modeling are identifying common binding elements in active compounds, generating potential ligand conformations, and determining the 3D relationships between pharmacophore elements. Pharmacophore models can be generated manually based on known active ligands or automatically using software. Receptor-based pharmacophore generation uses the 3D structure of the target protein to identify favorable binding sites. Overall, pharmacophore mapping is used in computer-aided drug design to identify novel ligands that interact with the same biological target.
A composite is a material made from two or more constituent materials with distinct properties. Nanocomposites contain one phase with nanoscale features like nanoparticles, nanotubes, or lamellar structures. Good interaction between the nanoparticles and matrix and good dispersion of particles in the matrix improve composite properties. Nanocomposites can be classified based on dimensionality of the nanomaterial or synthesis method and have applications like flame retardancy, high mechanical properties, and gas barrier performance. They are characterized using techniques like TEM, SEM, AFM, and XRD. Polymer/clay nanocomposites are an important type where clay layers exfoliate or intercalate in the polymer matrix.
This document discusses various chromatography techniques used to purify biomolecules, including affinity chromatography, ion exchange chromatography, size exclusion chromatography, and reversed phase chromatography. It provides details on how each technique separates molecules based on specific properties, such as biological recognition (affinity chromatography), charge (ion exchange chromatography), size (size exclusion chromatography), and hydrophobicity (reversed phase chromatography).
Introduction
Proteins
Function Of Protein And Their Properties
Protein Isolation And Purification
Methods Of Cell Lysis
Steps Of Protein Characterisation:
Determination Of Protein Concentration
Biuret Reaction
Lowry (Folin-Lowry) Method
UV- Spectroscopy
Assessment Of Protein Purity
SDS -Phage
Immunoblot
Surface Charge Analysis
Isoelectro Focusing
Ion Exchange Chromatography
Size, Shape And Conformation Analysis
2d-Electrophorasis
X-Ray Crytalliography
Protein Structure and Sequence Analysis
Edman Sequencing
Conclusion
References
This document discusses bioadhesive drug delivery systems. It begins by defining bioadhesion as the interfacial molecular forces that allow polymers to adhere to biological surfaces for extended periods of time. It then discusses various bioadhesive polymers, both natural and synthetic, that are commonly used in drug delivery formulations. These include polymers like acacia gum, alginic acid, carbomers, and hyaluronic acid. The document also outlines the three main mechanisms by which bioadhesion occurs: wetting and swelling of polymers, interpenetration of polymer chains with mucosal membranes, and formation of chemical bonds between entangled chains. Finally, it provides examples of different types of bioadhesive drug delivery formulations that can
This PhD thesis examines various biodegradable materials as alternatives to petroleum-based plastics. It studies nanocomposites made from polylactic acid and a PLA-PBAT blend reinforced with nanoclays and silica. The effects on mechanical properties, thermal stability, and degradation behavior are analyzed. A second part studies biocomposites of natural fibers like wood and flax in a biodegradable polymer matrix. The fiber type, adhesion, water absorption, and creep behavior under stress and temperature conditions are evaluated to understand material performance. The aim is to develop fully biodegradable composite materials with enhanced and controllable properties.
Affinity chromatography and gel filterationAshfaq Ahmad
Affinity chromatography is a technique that uses the specific binding properties of a molecule to purify it from a mixed sample. The process involves passing a sample over a column containing beads with affinity ligands attached. Proteins in the sample either bind tightly, bind loosely, or do not bind to the ligands on the beads. Multiple wash steps are used to remove non-binding and loosely binding proteins, leaving only the tightly bound protein of interest, which can then be eluted and collected in a purified form.
In silico discovery of histone methyltranferase 1juancarlosrise
This study investigated potential inhibitors of the histone methyltransferase SETD2 using in silico methods. Two pharmacophore models were generated and used to screen a database of 150,000 compounds, filtering it to 31,669 potential leads. Molecular docking ranked these by predicted binding energy, identifying 58 compounds with binding energies from -9.7 to -9.0 kcal/mol. Further refinement of the models and testing of top-scoring compounds may reveal inhibitors of histone methylation and cancer progression.
This document discusses nanoparticles, including their definition as submicron colloidal structures composed of polymers that are 10-1000nm in size. Nanoparticles can be nanospheres or nanocapsules and are useful for site-specific drug delivery. Some key advantages are achieving maximum drug effects with minimal side effects through active and passive targeting. The document outlines various polymer types used in nanoparticle production and evaluation methods like particle size, surface charge, drug loading efficiency and in vitro drug release.
Atomic force spectroscopy, a technique derived from Atomic Force Microscopy (AFM), allowed us to distinguish nonspecific and specific interactions between the acetolactate synthase enzyme (ALS) and anti-atrazine antibody biomolecules and the herbicides imazaquin, metsulfuron-methyl and atrazine. The presence of specific interactions increased the adhesion force (Fadh) between the AFM tip and the herbicides, which made the modified tip a powerful biosensor. Increases of approximately 132% and 145% in the Fadh values were observed when a tip functionalized with ALS was used to detect imazaquin and metsulfuron-methyl, respectively. The presence of specific interactions between the atrazine and the anti-atrazine antibody also caused an increase in the Fadh values (approximately 175%) compared to those observed when using an unfunctionalized tip. The molecular modeling results obtained with the ALS enzyme suggest that the orientation of the biomolecule on the tip surface could be suitable for allowing interaction with the herbicides imazaquin and metsulfuron-methyl
This document summarizes several common techniques used to purify and characterize proteins:
1. Proteins are first isolated from cells through homogenization and then separated from contaminants using techniques like salting out with ammonium sulfate or differential centrifugation.
2. Column chromatography techniques like size-exclusion chromatography, affinity chromatography, and ion exchange chromatography are used to further purify proteins based on properties like size, specific binding interactions, or charge.
3. Electrophoresis, isoelectric focusing, and techniques like amino acid analysis, Edman degradation, and enzymatic or chemical cleavage are then used to determine a protein's primary structure by separating peptide fragments and determining their sequence.
This document discusses various NMR techniques for ligand screening in drug discovery. It begins by providing background on the increasing role of NMR in drug research due to its ability to sensitively detect molecular interactions and provide structural information. The document then reviews both ligand-observed and target-observed NMR screening techniques, describing methods based on changes in molecular diffusion, relaxation, and intramolecular or intermolecular magnetization transfer upon ligand binding. Specific techniques discussed include saturation transfer difference (STD) NMR, transferred nuclear Overhauser effect (trNOE), and NOE pumping. The review concludes by noting the dual importance of NMR for drug screening and structure-based drug design.
Analytical techniques for separation or purification of proteinsrohini sane
A comprehensive presentation on Analytical techniques for separation or purification of proteins for MBBS , BDS, B Pharm & Biotechnology students to facilitate self- study.
Delivery of drugs in therapeutic concentration, to target receptor, is achieved by suitable polymers. Thus, generally it is not possible to target the drug by using a single polymer. Now a days polymer grafting plays a major role in targeted drug delivery system. Grafting may be done by different techniques. These grafted polymers are suitable for site specific drug delivery system. In can minimize the disadvantages of natural polymer and also synthetic polymer with goodness of both.
This document discusses molecular docking and different models used to describe molecular recognition between biomolecules. It begins by defining molecular recognition and docking, and describes early models like the lock-and-key and induced-fit models. It then discusses computational docking methods, including representing molecules, scoring docked poses, and search algorithms to generate poses. Flexibility is an important consideration, and methods to incorporate flexibility of both small molecule ligands and protein receptors are described.
Affinity chromatography is a technique used to separate biochemical compounds based on a reversible interaction between a compound and a ligand coupled to a chromatography matrix. It offers selectivity and can purify compounds that may be difficult to separate by other techniques. Key aspects of affinity chromatography include the matrix, ligand, ligand immobilization through various coupling methods, and elution techniques to reverse binding. Biomimetic dyes designed to mimic natural ligands can function as ligands in affinity chromatography.
Molecular imprinting is a technique for creating polymers with binding sites tailored to specific target molecules. It involves polymerizing a functional monomer around a template molecule, then removing the template to leave behind cavities that bind the target with high selectivity. Molecularly imprinted polymers (MIPs) can be used for applications like separations, sensing, and catalysis. The document discusses the history of molecular imprinting, different approaches like covalent and non-covalent imprinting, factors that influence MIP synthesis, and examples of their uses and advantages like selectivity and affinity for targets.
This seminar presentation summarizes polymer nanocomposites. It defines nanocomposites as multiphase solid materials with one phase having dimensions less than 100 nm. The major constituent is the polymer matrix and the minor constituent is nanoscale reinforcement materials like nanotubes, nanoplates, or nanoparticles. The advantages of nanoscale fillers over conventional fillers include low percolation thresholds, large interfacial areas, and short particle distances. Surface modification of nanofillers is important to prevent agglomeration and improve interfacial interactions. Common synthesis methods for polymer nanocomposites include melt compounding, solvent processing, and in situ polymerization. Polymer nanocomposites provide enhanced properties compared to
This document discusses affinity chromatography and biomimetic dyes. It begins by introducing affinity chromatography as a technique for separating substances based on their reversible interactions with immobilized ligands. It then provides historical background on affinity chromatography and describes various aspects of the technique including common matrices, ligand design and immobilization methods, and elution strategies. The document also discusses the use of biomimetic dyes as ligands for affinity chromatography, noting their low cost but lack of specificity. It describes strategies for designing new dye ligands with improved affinity and specificity for target proteins through mimicking natural ligands.
Chromatographic technique used for determining the biological activity of substances & to separate them from denatured or functionally different molecules. This type of chromatography is used to isolate enzymes & other proteins.
This document summarizes a study analyzing the lateral phase separation between phospholipids and adhesion macromolecules on two adhering membranes. The key findings are:
1) Adhesion macromolecules are modeled as long, flexible polymer chains anchored by their ends to anchors on the inner monolayers of two adjacent plasma membranes.
2) A field theory is developed to derive an expression for the mixing free energy of the phospholipid-anchor mixture on the membranes.
3) The phase diagram in the composition-temperature plane is extracted from the free energy expression. The phase separation is influenced by polymer chain length, solvent quality, and undulations between the coupled membranes.
Towards smart modeling of mechanical properties of a bio composite based on ...IJECEIAES
The main interest in many research problems in polymer bio composites and machine learning (ML) is the development of predictive models to one or several variables of interest by the use of suitable independent inputs or variables. Nevertheless, these fields have generally adopted several approaches, while bio composite behavior modeling is usually based on phenomenological theories and physical models. These latter are more robust and precise, but they are generally under the restricted predictive ability due to the particular set of conditions. On the other hand, Machine learning models can be highly efficient in the modeling phase by allowing the management of high and massive dimensional sets of data to predict the best behavior of bio composites. In this situation, biomaterial scientists would like to benefit from the comprehension and implementation of the powerful ML models to characterize or predict the bio composites. In this study, we implement a smart methodology employing supervised neural network models to predict the bio composites properties presenting more significant environmental and economic advantages than composites reinforced by synthetic fibers.
Robert Graff's research focuses on the synthesis, characterization, and applications of branched polymers. He has developed two strategies for producing nanostructured branched polymers with highly controlled structures using confined spaces and living chain growth mechanisms. This allows precise control over molecular weight, structure, and properties. The polymers have applications in catalysis, drug delivery, and more due to their globular structure and functional group concentration. Graff has published extensively on the synthesis techniques and characterization methods, and on exploring the polymers' properties and applications through collaborations.
This document summarizes a study that used molecular dynamics (MD) simulations and mesoscopic simulations to model the compatibility of polystyrene (PS) and poly(methyl methacrylate) (PMMA) blends. The study calculated Flory-Huggins interaction parameters via MD simulations which indicated immiscibility. Mesoscopic simulations then examined how the phase morphology of PS/PMMA blends was influenced by adding a block copolymer, applying shear, doping with nanoparticles, and surface roughness. The study provided insights into using inducing effects to control phase separation in polymer blends.
Affinity chromatography: Principles and applicationsHemant Khandoliya
Affinity chromatography separates proteins based on a reversible interaction between a protein and a ligand coupled to a chromatography matrix. There are several types of elution methods used including pH elution, ionic strength elution, and competitive elution. The matrix, ligand, and method of ligand immobilization via a spacer arm are important considerations for affinity chromatography.
The document discusses characterization techniques for molecularly imprinted polymers (MIPs). It describes several methods for analyzing particle size and shape, including SEM, TEM, and laser diffraction. Fourier transform infrared spectroscopy (FTIR), solid state NMR, elemental analysis, and X-ray diffraction are discussed for analyzing chemical properties. Adsorption capacity is characterized using isotherm models like Langmuir, Freundlich, and Langmuir-Freundlich, which describe homogeneous and heterogeneous binding sites. Binding studies are conducted using batch, frontal chromatography, radioligand, and calorimetry methods.
This thesis describes interlinked population balance and cybernetic models developed to simulate the simultaneous saccharification and fermentation of natural polymers like starch. Population balance modeling was used to describe the enzymatic depolymerization of polymers by enzymes. Cybernetic modeling was used to model the microbial response to environmental changes during fermentation. The two frameworks were successfully interlinked to capture the interaction between enzymatic kinetics and microbial behavior during the complex fermentation process.
This document summarizes a study that investigated how the nanostructure and microstructure of poly(L-lactic acid)/layered silicate hybrids affects their morphological and thermomechanical properties. Nanocomposites and microcomposites with various loadings of natural and organically-modified montmorillonite clay were produced by solution casting. Characterization techniques like XRD, TEM, AFM, and DSC were used to analyze the structure and properties. The results showed that at low clay content, exfoliation dominates, but at higher loadings both exfoliation and intercalation occur. The addition of organoclay improved thermal stability and the polymer's thermal behavior depended on the clay nature and
Discussing advances in Magnetic Bead coating technologies - Page 9 & 10 - Article from Joshua Soldo from Australian listed Biotech company Anteo Diagnostics ASX:ADO
Pharmacophore Modeling and Docking Techniques.pptDrVivekChauhan1
Pharmacophore modeling and molecular docking techniques are important computational methods used in drug design and discovery. Pharmacophore models identify the essential molecular features responsible for biological activity. Molecular docking predicts how drug molecules bind to protein targets. The document discusses key concepts like pharmacophores, bioisosterism, and molecular docking workflows. It also covers common docking software and factors that influence docking results like intramolecular forces and target preparation. Overall, the document provides an overview of pharmacophore modeling and molecular docking techniques that are widely applied in rational drug design.
This document discusses polymers and their applications in drug delivery. It begins with an introduction to polymers, including their classification and molecular structure. It then covers general mechanisms of drug release from polymers, including diffusion, degradation and swelling. Applications of polymers in conventional dosage forms and controlled drug delivery are presented. The document also discusses biodegradable polymers and natural polymers. It provides details on the classification, characteristics and selection of polymers for drug delivery.
STRUCTURE BASED DRUG DESIGN - MOLECULAR MODELLING AND DRUG DISCOVERYTHILAKAR MANI
This document discusses molecular modeling and structure-based drug design. It begins by outlining the general process of drug development from basic studies to clinical trials. It then discusses how structural bioinformatics can facilitate drug discovery through molecular design. Structure-based drug design starts with target identification and verification, then determining the 3D structure of the target protein. Key approaches discussed include structure-based ligand generation methods like docking and de novo design, as well as virtual library design and computer-aided drug design more broadly.
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EWOCS-I: The catalog of X-ray sources in Westerlund 1 from the Extended Weste...Sérgio Sacani
Context. With a mass exceeding several 104 M⊙ and a rich and dense population of massive stars, supermassive young star clusters
represent the most massive star-forming environment that is dominated by the feedback from massive stars and gravitational interactions
among stars.
Aims. In this paper we present the Extended Westerlund 1 and 2 Open Clusters Survey (EWOCS) project, which aims to investigate
the influence of the starburst environment on the formation of stars and planets, and on the evolution of both low and high mass stars.
The primary targets of this project are Westerlund 1 and 2, the closest supermassive star clusters to the Sun.
Methods. The project is based primarily on recent observations conducted with the Chandra and JWST observatories. Specifically,
the Chandra survey of Westerlund 1 consists of 36 new ACIS-I observations, nearly co-pointed, for a total exposure time of 1 Msec.
Additionally, we included 8 archival Chandra/ACIS-S observations. This paper presents the resulting catalog of X-ray sources within
and around Westerlund 1. Sources were detected by combining various existing methods, and photon extraction and source validation
were carried out using the ACIS-Extract software.
Results. The EWOCS X-ray catalog comprises 5963 validated sources out of the 9420 initially provided to ACIS-Extract, reaching a
photon flux threshold of approximately 2 × 10−8 photons cm−2
s
−1
. The X-ray sources exhibit a highly concentrated spatial distribution,
with 1075 sources located within the central 1 arcmin. We have successfully detected X-ray emissions from 126 out of the 166 known
massive stars of the cluster, and we have collected over 71 000 photons from the magnetar CXO J164710.20-455217.
ESPP presentation to EU Waste Water Network, 4th June 2024 “EU policies driving nutrient removal and recycling
and the revised UWWTD (Urban Waste Water Treatment Directive)”
ANAMOLOUS SECONDARY GROWTH IN DICOT ROOTS.pptxRASHMI M G
Abnormal or anomalous secondary growth in plants. It defines secondary growth as an increase in plant girth due to vascular cambium or cork cambium. Anomalous secondary growth does not follow the normal pattern of a single vascular cambium producing xylem internally and phloem externally.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
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The pygmy halfbeak Dermogenys colletei, is known for its viviparous nature, this presents an intriguing case of relatively low fecundity, raising questions about potential compensatory reproductive strategies employed by this species. Our study delves into the examination of fecundity and the Gonadosomatic Index (GSI) in the Pygmy Halfbeak, D. colletei (Meisner, 2001), an intriguing viviparous fish indigenous to Sarawak, Borneo. We hypothesize that the Pygmy halfbeak, D. colletei, may exhibit unique reproductive adaptations to offset its low fecundity, thus enhancing its survival and fitness. To address this, we conducted a comprehensive study utilizing 28 mature female specimens of D. colletei, carefully measuring fecundity and GSI to shed light on the reproductive adaptations of this species. Our findings reveal that D. colletei indeed exhibits low fecundity, with a mean of 16.76 ± 2.01, and a mean GSI of 12.83 ± 1.27, providing crucial insights into the reproductive mechanisms at play in this species. These results underscore the existence of unique reproductive strategies in D. colletei, enabling its adaptation and persistence in Borneo's diverse aquatic ecosystems, and call for further ecological research to elucidate these mechanisms. This study lends to a better understanding of viviparous fish in Borneo and contributes to the broader field of aquatic ecology, enhancing our knowledge of species adaptations to unique ecological challenges.
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Slides from:
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Track: Artificial Intelligence
https://www.etran.rs/2024/en/home-english/
Or: Beyond linear.
Abstract: Equivariant neural networks are neural networks that incorporate symmetries. The nonlinear activation functions in these networks result in interesting nonlinear equivariant maps between simple representations, and motivate the key player of this talk: piecewise linear representation theory.
Disclaimer: No one is perfect, so please mind that there might be mistakes and typos.
dtubbenhauer@gmail.com
Corrected slides: dtubbenhauer.com/talks.html
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
The use of Nauplii and metanauplii artemia in aquaculture (brine shrimp).pptxMAGOTI ERNEST
Although Artemia has been known to man for centuries, its use as a food for the culture of larval organisms apparently began only in the 1930s, when several investigators found that it made an excellent food for newly hatched fish larvae (Litvinenko et al., 2023). As aquaculture developed in the 1960s and ‘70s, the use of Artemia also became more widespread, due both to its convenience and to its nutritional value for larval organisms (Arenas-Pardo et al., 2024). The fact that Artemia dormant cysts can be stored for long periods in cans, and then used as an off-the-shelf food requiring only 24 h of incubation makes them the most convenient, least labor-intensive, live food available for aquaculture (Sorgeloos & Roubach, 2021). The nutritional value of Artemia, especially for marine organisms, is not constant, but varies both geographically and temporally. During the last decade, however, both the causes of Artemia nutritional variability and methods to improve poorquality Artemia have been identified (Loufi et al., 2024).
Brine shrimp (Artemia spp.) are used in marine aquaculture worldwide. Annually, more than 2,000 metric tons of dry cysts are used for cultivation of fish, crustacean, and shellfish larva. Brine shrimp are important to aquaculture because newly hatched brine shrimp nauplii (larvae) provide a food source for many fish fry (Mozanzadeh et al., 2021). Culture and harvesting of brine shrimp eggs represents another aspect of the aquaculture industry. Nauplii and metanauplii of Artemia, commonly known as brine shrimp, play a crucial role in aquaculture due to their nutritional value and suitability as live feed for many aquatic species, particularly in larval stages (Sorgeloos & Roubach, 2021).
Phenomics assisted breeding in crop improvementIshaGoswami9
As the population is increasing and will reach about 9 billion upto 2050. Also due to climate change, it is difficult to meet the food requirement of such a large population. Facing the challenges presented by resource shortages, climate
change, and increasing global population, crop yield and quality need to be improved in a sustainable way over the coming decades. Genetic improvement by breeding is the best way to increase crop productivity. With the rapid progression of functional
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the complex characteristics of multiple gene, owing to a lack of crop phenotypic data. Efficient, automatic, and accurate technologies and platforms that can capture phenotypic data that can
be linked to genomics information for crop improvement at all growth stages have become as important as genotyping. Thus,
high-throughput phenotyping has become the major bottleneck restricting crop breeding. Plant phenomics has been defined as the high-throughput, accurate acquisition and analysis of multi-dimensional phenotypes
during crop growing stages at the organism level, including the cell, tissue, organ, individual plant, plot, and field levels. With the rapid development of novel sensors, imaging technology,
and analysis methods, numerous infrastructure platforms have been developed for phenotyping.
ESR spectroscopy in liquid food and beverages.pptxPRIYANKA PATEL
With increasing population, people need to rely on packaged food stuffs. Packaging of food materials requires the preservation of food. There are various methods for the treatment of food to preserve them and irradiation treatment of food is one of them. It is the most common and the most harmless method for the food preservation as it does not alter the necessary micronutrients of food materials. Although irradiated food doesn’t cause any harm to the human health but still the quality assessment of food is required to provide consumers with necessary information about the food. ESR spectroscopy is the most sophisticated way to investigate the quality of the food and the free radicals induced during the processing of the food. ESR spin trapping technique is useful for the detection of highly unstable radicals in the food. The antioxidant capability of liquid food and beverages in mainly performed by spin trapping technique.
2. Int. J. Mol. Sci. 2006, 7 156
subjected to heat in order to initiate polymerization. During polymerization, the complexes formed
between the template molecule and the functional monomers will be stabilized within the resulting rigid,
highly cross-linked polymer. After polymerization and extracted out of the template molecule, the
resulting imprinted polymer possessing a permanent memory for the imprint species are formed,
enabling the resultant polymer selectively to rebind the imprint molecule from a mixture of closely
related compounds. The three-dimensional cavities that are complementary in both shape and chemical
functionality arrangement to those of the template be left in the polymer matrix and the high degree of
cross-linking enables the microcavities to maintain their shape after removal of the template, and thus,
the functional groups are held in an optimal configuration for rebinding the template, allowing the
receptor to `recognize' the original substrate [4-5]. Molecularly imprinted polymers demonstrate very
good thermal and chemical stability and can be used in aggressive media [6]. MIP possess several
advantages over their biological counterparts including low cost, ease of preparation, storage stability,
repeated operations without loss of activity, high mechanical strength, durability to heat and pressure,
and applicability in harsh chemical media. As a technique for the creation of artificial receptor-like
binding sites with a ‘memory’ for the shape and functional group positions of the template molecule,
molecular imprinting has become increasingly attractive in many fields of chemistry and biology,
particularly as an affinity material for sensors [7-11], binding assays [12], artificial antibodies [13-14],
adsorbents for solid phase extraction [15-19], and chromatographic stationary phases [20-23].
2. Category of MIP
Essentially, two kinds of molecular imprinting strategies have been established based on covalent
bonds or non-covalent interactions between the template and functional monomers (Figure 1). In both
cases, the functional monomers, chosen so as to allow interactions with the functional groups of the
imprinted molecule, are polymerized in the presence of the imprinted molecule. The special binding
sites are formed by covalent or, more commonly, non-covalent interaction between the functional group
of imprint template and the monomer, followed by a crosslinked co-polymerization [24]. Of the two
strategies, the non-covalent approach has been used more extensively due to follow three reasons:
(1) Non-covalent protocol is easily conducted, avoiding the tedious synthesis of prepolymerization
complex.
(2) Removal of the template is generally much easier, usually accomplished by continuous extraction.
(3) A greater variety of functionality can be introduced into the MIP binding site using non-covalent
methods.
3. Int. J. Mol. Sci. 2006, 7 157
Figure 1. Schematic representation of covalent and non-covalent molecular imprinting procedures
2.1. Covalent Approach
In covalent approach, the imprinted molecule is covalently coupled to a polymerizable molecule. The
binding of this type of polymer-relies on reversible covalent bonds. After copolymerization with
crosslinker, the imprint molecule is chemically cleaved from the highly crosslinked polymer. Wulff
[25-26] and co-workers first produced MIP by synthesizing specific sugar or amino acid derivatives
which contained a polymerisable function such as vinylphenylboronate by covalent imprinting methods.
After polymerization they hydrolyzed the sugar moiety and used the polymer for selective binding and
result shown that for covalent molecular imprinting, selectivity of MIP increases with maximization of
crosslinker. Moreover, the requirements of covalent imprinting are different than those for non-covalent
imprinting, particularly with respect to ratios of functional monomer, crosslinker, and template.
However, since the choice of reversible covalent interactions and the number of potential templates are
substantially limited, reversible covalent interactions with polymerizable monomers are fewer in
number and often require an acid hydrolysis procedure to cleave the covalent bonds between the
template and the functional monomer.
2.2. Non-covalent Approach
Non-covalent approach is the most frequently used method to prepare MIP due to its simplicity.
During the non-covalent approach, the special binding sites are formed by the self-assembly between
the template and monomer, followed by a crosslinked co-polymerization [27-28]. The imprint
molecules interact, during both the imprinting procedure and the rebinding, with the polymer via
non-covalent interactions, e.g. ionic, hydrophobic and hydrogen bonding. The non-covalent imprinting
approach seems to hold more potential for the future of molecular imprinting due to the vast number of
compounds, including biological compounds, which are capable of non-covalent interactions with
functional monomers [29-30]. Limits to the non-covalent molecular imprinting are set by the peculiar
molecular recognition conditions. Most of fact, the formation of interactions between monomers and
4. Int. J. Mol. Sci. 2006, 7 158
the template are stabilized under hydrophobic environments, while polar environments disrupt them
easily. Another limit is represented by the need of several distinct points of interactions: some
molecules characterized by a single interacting group, such as an isolated carboxyl, generally give
imprinted polymers with very limited molecular recognition properties, which have little interest in
practical applications.
Understanding the basic optimization of non-covalent methods is important for two reasons: the
methodology is far easier than covalent methods, and it produces higher affinity binding sites, versus
covalent methods. The trends in binding and selectivity in non-covalently imprinted polymers are
explained best by incorporates multiple functional monomers for the highest affinity binding sites. The
increased number of binding interactions in the polymer binding site may account for greater fidelity
of the site, and thus impart greater affinity and selectivity to the site. This would suggest that the
number of functional groups in the polymer binding site is not determined directly by the solution
phase pre-polymer complex; rather, it is determined during polymerization. Because of the difficulty
to characterizing the binding site structures during and after polymerization, the actual events
determining the final binding site structure are still a main challenge.
3. Molecular Recognition of MIP
Despite the wealth of literature on molecular imprinting technology that has been published within
past decades, the mechanisms of recognition and their rational control appear not entirely understood,
thus inhibiting optimization of the imprinting strategy. Molecular recognition ability is dependent on
several factors, such as shape complementarity, functional complementarity, contributions from the
surrounding environment. As for the functional complementarity, even though all non-covalent
interactions are applicable to the molecular recognition between a target molecule and a molecular
recognition site formed by a molecular imprinting, the nature of the template, monomers and the
polymerization reaction itself determine the quality and performance of the polymer product.
Moreover, the quantity and quality of the molecularly imprinted polymer recognition sites is a direct
function of the mechanisms and extent the monomer–template interactions present in the
pre-polymerization mixture. The recognition of the polymer constitutes an induced molecular memory,
which makes the recognition sites capable of selectively recognizing the imprint species.
The imprinted molecules interact, during both the imprinting procedure and the rebinding, with the
polymer via non-covalent interactions, e.g. ionic, hydrophobic and hydrogen bonding [31]. Hydrogen
bond is most often applied as a molecular recognition interaction of molecularly imprinted polymers.
From this, acrylic acid and methacrylic acid have usually been adopted as functional monomers since
carboxyl group functions as a hydrogen donor and a hydrogen acceptor at the same time. These
non-covalent interactions are easily reversed, usually by a wash in aqueous solution of an acid, a base,
or methanol, thus facilitating the removal of the template molecule from the network after
polymerization. In addition to the better versatility of this more general approach, it allows fast and
reversible binding of the template.
5. Int. J. Mol. Sci. 2006, 7 159
Mosbach et al. [32-34] has shown various examples of MIP prepared from different functional
monomers (e.g. methacrylic acid (MAA) and acrylamide (AM)) and a cross-linking copolymer (e.g.
ethyleneglycol dimethacrylate (EDMA)) in porogenic solvents such as chloroform, toluene,
tetrahydrofuran and acetonitrile. Most MIP are prepared by non-covalent imprinting and the common
systems are based on methacrylic monomers, such as methacrylic acid because its carboxyl group is
the most common hydrogen-bonding and acidic functional group in molecular imprinting, cross-linked
with EDMA. Molecularly imprinted polymers prepared with the trifunctional crosslinkers
pentaerythritol triacrylate and trimethlolpropane trimethacrylate (TRIM) were shown to be superior to
those prepared with EDMA, in that higher load capacities and better resolution were obtained.
Nicholls [35-36] studied thermodynamic considerations of MIP recognition. He explained that the
extent of template complexation at equilibrium is governed by the change in Gibbs free energy of
formation of each mode of template–functional monomer interaction. As the prearrangement phase is
under thermodynamic control, the monomer(s)–template complex is not subjected to conformational
strains and unfavourable vander Waals interactions. Furthermore, MIP only undergoes limited changes
in its conformation during the recognition of the template because of its high degree of cross-linking.
Since both polymerization and rebinding processes occurred generally in lipophylic solvents,
hydrophobic interactions can be considered negligible.
Kim et al. [37] investigated and compared the thermodynamic properties of copolymers imprinted
for Fmoc-L-tryptophan and prepared by two different methods: in situ polymerization and traditional
bulk method. The thermodynamic properties of the two different MIP showed that three types of
binding sites coexist on their surface. The highest energy sites adsorb only the imprinted molecule or
template. Most of the intermediate energy sites adsorb both the template and its antipode, although
part of them may adsorb only the template. Finally, the lowest energy sites provide nonselective
interactions of both the template and its antipode. On the nonimprinted copolymer, there are only two
types of sites. The high-energy sites have a slightly lower energy that the intermediate sites of the MIP
and the low-energy sites have properties close to those of the lowest energy sites on the MIP. The
monolithic MIP has fewer nonselective sites than the bulk MIP.
A layer of mineral oil was deposited onto the surface of the polymer in order to create a
hydrophobic environment in the binding sites and to improve the recognition properties of the polymer
in polar solvents was investigated by Piletska [38]. The performances of polymers in acetonitrile
showed that the modified polymers possessed significantly increased selectivity as compared with
non-treated ones. The three-fold improvement of recognition ability to template (cocaine) was
achieved; at the same time, for non-specific molecule (morphine) the improvement was only 1.3 times.
The investigation of the stability of mineral oil coating on the polymer surface suggested that the
effect produced is stable over a long period of time. This approach could be used to broaden the range
of experimental conditions where molecularly imprinted polymers can perform successfully.
6. Int. J. Mol. Sci. 2006, 7 160
4. Effecting of Special Molecular Recognition
4.1. Optimization of the Polymer Structure
The synthesis of molecularly imprinted polymers is a chemically complex pursuit and demands a
good understanding of chemical equilibrium, molecular recognition theory, thermodynamics and
polymer chemistry in order to ensure a high level of molecular recognition [39-43]. The polymers
should be rather rigid to preserve the structure of the cavity after splitting off the template. On the
other hand, a high flexibility of the polymers should be present to facilitate a fast equilibrium between
release and reuptake of the template in the cavity. These two properties are contradictory to each other,
and a careful optimization became necessary. The challenge of designing and synthesizing a
molecularly imprinted polymer can be a daunting prospect to the uninitiated practitioner, not least
because of the sheer number of experimental variables involved, e.g. the nature and levels of template,
functional monomer(s), cross-linker(s), solvent(s) and initiator, the method of initiation and the
duration of polymerization. Moreover, optimization of the imprinted products is made more difficult
due to the fact that there are many variables to consider, some or all of which can potentially impact
upon the chemical, morphological and molecular recognition properties of the imprinted materials.
Fortunately, in some instances it is possibly to rationally predict how changing any one such variable,
e.g. the cross-link ratio, is likely to impact upon these properties [44-48].
4.2. Template
The template is central importance and it directs organization of the functional groups pendent to
the functional monomers in all molecular imprinting processes. In terms of compatibility with free
radical polymerization, templates should ideally be chemically inert under the polymerization
conditions, thus alternative imprinting strategies may have to be sought if the template can participate
in radical reactions or is for any other reason unstable under the polymerization conditions. The
following are legitimate questions to ask of a template: (1) Does the template bear any polymerisable
groups? (2) Does the template bear functionality that could potentially inhibit or retard a free radical
polymerization? (3) Will the template be stable at moderately elevated temperatures or upon exposure
to UV irradiation? The imprinting of small, organic molecules (e.g., pharmaceuticals, pesticides,
amino acids and peptides, nucleotide bases, steroids, and sugars) is now well established and
considered almost routine. Optically active templates have been used in most cases during
optimization. In these cases the accuracy of the structure of the imprint (the cavity with binding sites)
could be measured by its ability for racemic resolution, which was tested either in a batch procedure or
by using the polymeric materials as chromatographic supports.
One of the many attractive features of the molecular imprinting method is that it can be applied to a
diverse range of analytes, however, not all templates are directly amenable to molecular imprinting
processes. Most routine MIP were using small organic molecules as template. Although specially
adapted protocols have been proposed for larger organic compounds, e.g., proteins, cells, imprinting of
much larger structures is still a challenge. The primary reason is the fact that larger templates are less
rigid and thus do not facilitate creation of well-defined binding cavities during the imprinting process.
7. Int. J. Mol. Sci. 2006, 7 161
Furthermore, the secondary and tertiary structure of large biomolecules such as proteins may be
affected when exposed to the thermal or photolytic treatment involved in the synthesis of imprinted
polymers. Rebinding is also more difficult, since large molecules such peptides and proteins do not
readily penetrate the polymer network for reoccupation of binding pockets.
4.3. Monomers
The careful choice of functional monomer is one of the utmost importance to provide
complementary interactions with the template and substrates. (Figure 2) For covalent molecular
imprinting, the effects of changing the template to functional monomer ratio is not necessary because
the template dictates the number of functional monomers that can be covalently attached; furthermore,
the functional monomers are attached in a stoichiometric manner. For non-covalent imprinting, the
optimal template /monomer ratio is achieved empirically by evaluating several polymers made with
different formulations with increasing template [49]. The underlying reason for this is thought to
originate with the solution complex between functional monomers and template, which is governed by
Le Chatelier’s principle. Applying Le Chatelier’s principle to the complex formed prior to
polymerization, increasing the concentration of components or binding affinity of the complex in the
prepolymerization mixture would predict an increase in the pre-polymer complex. Correspondingly,
there is an increase the number of final binding sites in the imprinted polymer, resulting in an
increased binding or selectivity factor per gram of polymer.
From the general mechanism of formation of MIP binding sites, functional monomers are
responsible for the binding interactions in the imprinted binding sites, and for non-covalent molecular
imprinting protocols, are normally used in excess relative to the number of moles of template to favor
the formation of template-functional monomer assemblies. It is very important to match the
functionality of the template with the functionality of the functional monomer in a complementary
fashion (e.g. H-bond donor with H-bond acceptor) in order to maximise complex formation and thus
the imprinting effect. Higher retention and resolution was finding by the two co-monomer imprinting
polymer than the single monomer imprinting polymer, which indicated an increase in the affinity of
the MIP with the sample as a result of the cooperation effect of the binding sites. However, it’s
important to bear reactivity ratios of the monomers to ensure those copolymerisations are feasible.
8. Int. J. Mol. Sci. 2006, 7 162
CH2
OH
O
acrylic acid
CH2
OH
O
methacrylic acid
H3C
CH2
OCH3
O
methyl methacrylic acid
H3C OH
O
H2C
p-vinylbenzoic acid
O
H2C
O OH
OH
itaconic acid
CH3
H2C
4-ethystyrene
H2C
4-ethystyrene
N
H2C
N
H2C
4-vinylpyridine
N
N
H2C
2-vinylpyridine 1-vinylimidazole
CH2SO3H
CH3
CH3
CH2
O
acrylamido-2-methyl-1-propane- sulphonic acid
NH2
OH2C
NH2
OH2C
H3C
acrylamide methacrylamide
H2C NHO
O
styrene trans-3-(3-pyridyl)-acrylic acid
Figure 2. Common functional monomers used in non-covalent molecular imprinting procedures.
4.4. Crosslinkers
The selectivity is greatly influenced by the kind and amount of cross-linking agent used in the
synthesis of the imprinted polymer. The careful choice of functional monomer is another importance
choice to provide complementary interactions with the template and substrates (Figure 3). In an
imprinted polymer, the cross-linker fulfils three major functions: First of all, the cross-linker is
important in controlling the morphology of the polymer matrix, whether it is gel-type, macroporous or
a microgel powder. Secondly, it serves to stabilize the imprinted binding site. Finally, it imparts
mechanical stability to the polymer matrix. From a polymerization point of view, high cross-link ratios
are generally preferred in order to access permanently porous (macroporous) materials and in order to
be able to generate materials with adequate mechanical stability. So the amount of cross-linker should
be high enough to maintain the stability of the recognition sites. These may be because the high degree
of cross-linking enables the microcavities to maintain three-dimensional structure complementary in
both shape and chemical functionality to that of the template after removal of the template, and thus,
the functional groups are held in an optimal configuration for rebinding the template, allowing the
receptor to `recognize' the original substrate. Polymers with cross-link ratios in excess of 80% are
9. Int. J. Mol. Sci. 2006, 7 163
often be used. Quite a number of cross-linkers compatible with molecular imprinting are known, and a
few of which are capable of simultaneously complexing with the template and thus acting as
functional monomers.
4.5. Porogenic solvents
Porogenic solvents play an important role in formation of the porous structure of MIP, which known
as macroporous polymers. It is known that the nature and level of porogenic solvents determines the
strength of non-covalent interactions and influences polymer morphology which, obviously, directly
affects the performance of MIP. Firstly, template molecule, initiator, monomer and cross-linker have
to be soluble in the porogenic solvents. Secondly, the porogenic solvents should produce large pores,
in order to assure good flow-through properties of the resulting polymer. Thirdly, the porogenic
solvents should be relatively low polarity, in order to reduce the interferences during complex
formation between the imprint molecule and the monomer, as the latter is very important to obtain
high selectivity MIP.
Porogenic solvents with low solubility phase separate early and tend to form larger pores and
materials with lower surface areas. Conversely, porogenic solvents with higher solubility phase
separate later in the polymerization provide materials with smaller pore size distributions and greater
surface area. More specifically, use of a thermodynamically good solvent tends to lead to polymers
with well developed pore structures and high specific surface areas, use of a thermodynamically poor
solvent leads to polymers with poorly developed pore structures and low specific surface areas.
However, the binding and selectivity in MIP is not appeared to dependent on a particular porosity.
Although the results of molecular recognition weaken with the polar of the porogenic solvents
increasing, however, it is important to stress that in some cases sufficiently strong template: monomer
interactions have been observed in rather polar solvents (e.g. methanol/water). Increasing the volume
of porogenic solvents increases the pore volume. Besides its dual roles as a solvent and as a pore
forming agent, the solvent in a non-covalent imprinting polymerization must also be judiciously
chosen such that it simultaneously maximizes the likelihood of template, functional monomer complex
formation. Normally, this implies that apolar, non-protic solvents, e.g. toluene, are preferred as such
solvents stabilize hydrogen bonds, however if hydrophobic forces are being used to drive the
complexation then water could well be the solvent of choice.
10. Int. J. Mol. Sci. 2006, 7 164
CH2
H
N
H
N
CH2
OO
N,N'-1,4-phenylenediacrylamine
CH2
H
N
H
N
CH2
O O
N,N'-methylenediacrylamide
H
N
CH2
O
CH2
O
3,5-bis(acryloylamido)benzoic acid
H
N
CO2H
CH2
H3C
O
O
CH3
O O
O
ethylene glycol dimethacrylate
CH2
H2C
divinylbenzene
CH2
O
H
N
O
O
CH2
N,O-bisacryloyl-phenylalaninol
CH3
CH2
H3C
H2C
1,3-diisopropenyl benzene
CH3
H2C O
O
CH2
O
O
CH2
tetramethylene dimethacrylate
N
H
N
CH2
H
N
H2C
O O
2,6-bisacryloylamidopyridine
N
N
O
CH2
O
H2C
1,4-diacryloyl piperazine
OH2C
CH3
O
O
O
CH3
CH2
O
O
CH3
H2C
trimethylpropane trimethacrylate
CH3
OH2C
O
O
O
CH2
O
O
H2C
O
CH2
O
pentaerythritol tetraacrylate
Figure 3. Chemical structure of common cross-linkers used in non-covalent molecular imprinting.
11. Int. J. Mol. Sci. 2006, 7 165
4.6. Initiators
Many chemical initiators with different chemical properties can be used as the radical source in free
radical polymerization (Figure 4). Normally they are used at low levels compared to the monomer, e.g.
1 wt. %, or 1 mol. % with respect to the total number of moles of polymerisable double bonds. The
rate and mode of decomposition of an initiator to radicals can be triggered and controlled in a number
of ways, including heat, light and by chemical/electrochemical means, depending upon its chemical
nature. For example, the azoinitiator azobisisobutyronitrile (AIBN) can be conveniently decomposed
by photolysis (UV) or thermolysis to give stabilised, carbon-centred radicals capable of initiating the
growth of a number of vinyl monomers. As an illustrative example of the use of AIBN, or indeed other
initiators, to polymerize vinyl monomers, AIBN can polymerize methylmethacrylate under thermal or
photochemical conditions to give poly(methyl methacrylate).
Oxygen gas retards free radical polymerizations, thus in order to maximize the rates of monomer
propagation, ensure good batch-to-batch reproducibility of polymerizations, removal of the dissolved
oxygen from monomer solutions immediately prior to proliferation is advisable. Removal of dissolved
oxygen can be achieved simply by ultrasonication or by sparging of the monomer solution by an inert
gas, e.g. nitrogen or argon.
H3C N
CN
CH3
N
CH3
CH3
CN
azobisisobutyronitrile
N N
CN
CH3
CH3
CN CH3
CH3
H3C
CH3
azobisdimethylvaleronitrile
N N
CN
CH3
CH3
CN
O
HO
OH
O
4,4'-azo(4-cyanovaleric acid)
OOMe
OMe
dimethylacetal of benzil
O
O
O
O
benzoylperoxide
Figure 4. Chemical structure of common initiators used in non-covalent molecular imprinting
4.7. Polymerization condition
Several studies have shown that polymerization of MIP at lower temperatures forms polymers with
greater selectivity versus polymers made at elevated temperatures. Usually, most people using 60℃
as the polymerization temperature. However, the initiation of the polymerization reaction was very fast
and therefore hard to control at this temperature and resulted in low reproducibility of molecular
imprinted polymer. Furthermore, the relatively high temperatures have a negative impact on the
complex stability, which reduced the reproducibility of the monolithic stationary phases and produced
high column pressure drops. Thus, the relatively low temperatures of with a prolonged reaction time
12. Int. J. Mol. Sci. 2006, 7 166
were selected in order to yield a more reproducible polymerization. Where complexation is driven by
hydrogen bonding then lower polymerization temperatures are preferred, and under such
circumstances photochemically active initiators may well be preferred as these can operate efficiently
at low temperature. For example, Mosbach et al. [50-51] presented a study on enantioselectivity of
l-PheNHPh imprinted polymers, one polymer being thermally polymerized at 60℃, the other
photochemically polymerized at 0℃. The results showed that better selectivity is obtained at the lower
temperature versus the identical polymers thermally polymerized. The reason for this has again been
postulated on the basis of Le Chatelier’s principle, which predicts that lower temperatures will drive
the pre-polymer complex toward complex formation, thus increasing the number and, possibly, the
quality of the binding sites formed.
5. Preparation Methods of MIP
5.1. Bulk Polymerization
Molecularly imprinted polymers can be prepared in a variety of physical forms to suit the final
application desired (Table 1). The conventional method for preparing MIP is via solution
polymerization followed by mechanical grinding of the resulting bulk polymer generated to give small
particles and sieve the particles into the desired size ranges, which diameters usually in the micrometer
range [52-53]. This method, by far the most popular, presents many attractive properties, especially to
newcomers. In fact, it is fast and simple in its practical execution and it does not require particular
operator skills or sophisticated instrumentation. Particle sizes <25 µm are usually used in
chromatographic studies [54]. Such ground and sieved particles have been packed into conventional
HPLC columns, immobilized on TLC plates, and entrapped in capillary columns using acrylamide gels
or silicate matrices.
Although bulk polymerization is simple, and optimization of imprinting conditions is relatively
straightforward, however, bulk polymerization method presents many drawbacks anyway. First of all,
the particles obtained after the last sieving step have a highly irregular in size and shape, some
interaction sites are destroyed during grinding, and thus lead to a negative impact on chromatographic
performance and lower MIP loading capacity with respect to theoretical values. Moreover, the
procedure of grinding and sieving is cumbersome, and it causes a substantial loss of useful polymer,
that can be estimated between 50 and 75% of the initial amount of bulk material. Since a portion of
polymer can only be used as packing material, this method suffered high consumption of the template
molecules. Last, but not least, due to its exothermical nature, bulk polymerization cannot be scaled-up
without danger of sample overheating.
Gonzalez et al. [55] systemic studied the non-covalent MIP synthesized by “bulk” polymerization
using digoxin as template. These polymers were synthesized under different conditions, i.e., changing
the functional monomers employed (methacrylic acid or 2-vinylpyridine), the porogenic solvents
(acetonitrile or dichloromethane) used, different polymerization and extraction processes were used.
The polymerization process was proceeding either under UV light or in a thermostat-controlled water
bath. This produced polymers with different structural conformations and characteristics (hardness,
13. Int. J. Mol. Sci. 2006, 7 167
porosity, stiffness, loading capacity, strength, etc.). The binding capacity, binding specificity and
chemical and thermal capacities of these MIP were found to depend directly on the characteristics of
their surface morphology.
Molecular imprinting of 2-aminopyridine (2-apy) in bulk polymerizations of acrylic and sol–gel
based polymers has been synthesized by O’Mahony [56]. Both polymeric systems reveal varying
degrees of affinity in rebinding the original template as well as a number of structural analogues.
Rebinding was conducted in chloroform, acetonitrile and methanol in order to assess the role of
hydrogen bonding in imprinting. The acrylic imprinted polymer retained approximately 50% of the
template in rebinding studies in chloroform compared to 100% for the sol–gel. However, this higher
affinity for the sol–gel was accompanied by a higher degree of non-specific binding. The acrylic
polymer exhibited little discrimination between imprinted and reference polymers for 3-aminopyridine
(3-apy) indicating the high selectivity of the MIP polymer for 2-apy relative to 3-apy.
Table 1. Summary of MIP prepared by different methods.
MIP format Benefits Limitations
Bulk polymerization
Suspension polymerization
Multi-step swelling
polymerization
Precipitation polymerization
Surface polymerization
In-situ polymerization
Polymerization simplicity and
universality,
No require particular skills or
sophisticated instrumentation
spherical particles,
Highly reproducible results,
Large scale possible
Monodisperse beads of
controlled diameter,
Excellent particle for HPLC
Imprinted microspheres,
Uniform size and high yields
Monodisperse product,
Thin imprinted layers
One-step, in-situ preparation,
Cost-efficient, good porosity
Tedious procedures of grinding,
sieving, and column packing,
Irregular particle in size and shape,
low performance.
Phase partitioning of complicates
system,
Water is incompatible with most
imprinted procedures, Specialist
surfactant polymers required
Complicated procedures and
reaction conditions,
Need for aqueous emulsions,
Large amount of template
High dilution factor
Complicated system,
Time consuming
Extensive optimization required
for each new template system
5.2. Multi-step Swelling Polymerization
In recent years, much effort has been dedicated to developing alternative methods to prepare
imprinted stationary phases, which are superior in terms of efficiency and mass transfer properties.
14. Int. J. Mol. Sci. 2006, 7 168
Micrometer-sized spherical imprinted polymers with narrow size distribution have been prepared
through several techniques [57-59]. Uniformed spherical particles have been obtained by using
multi-step swelling method [60-63]. Particles can be prepared directly in the form of spherical beads
of controlled diameter. Beads synthesized in this way can be rendered magnetic through inclusion of
iron oxide particles. Although particles obtained using this technique are comparatively monodisperse
in size and shape and well suited for chromatographic applications, however, fairly complicated
procedures and reaction conditions are required, and the aqueous suspensions used in this technique
could interfere with the imprinting and thus lead to a decrease in selectivity. The requirement for
aqueous emulsions can interfere with the imprinting process and the selectivity of these particles is
still not completely satisfactory.
Uniformly sized MIP for d-chlorpheniramine (CP) and -brompheniramine (BP) prepared by a
multi-step swelling polymerization method and evaluated using a mixture of phosphate buffer and
acetonitrile as mobile phase [64]. CP and BP enantiomers were retained the most as a monovalent
cation on MAA-co-EDMA polymers and a divalent cation on TFMAA-co-EDMA polymers. Ion
exchange and hydrophobic interactions could mainly work for the retention and enantioseparation of
CP and BP on both MAA-co-EDMA and TFMAA-co-EDMA polymers in hydro-organic mobile
phases.
5.3. Suspension Polymerization
A rather simple method for the preparation of imprinted supports not requiring mechanical grinding
is suspension polymerization, which yields aggregates of spherical particles, if the system is
sufficiently dilute, uniformly sized microspheres. To avoid above interference in multi-step swelling
method, suspension polymerization in perfluorocarbon solvents has been studied [65-66]. In two-phase
systems, the use of liquid perfluorocarbons instead of water as the continuous phase might be
preferred since water may have a detrimental effect on the non-covalent complex between monomers
and imprint molecule. Although regular molecularly imprinted microspheres have been prepared and
excellent chromatographic performance was obtained from polymer beads produced by use of these
methods and selectivity was good even at high flow rates, unfortunately, the specialized
perfluorocarbon solvent and fluorinated surfactant impose limits on the applicability and practicality
of this method.
Bovine serum albumin-imprinted polyacrylamide gel beads were synthesized via inverse-phase seed
suspension polymerization, using high-density crosslinked gel beads as core, low-density crosslinked
polyacrylamide gel as imprinting shell [67]. The selectivity test showed that imprinting gel beads
exhibited good recognition for template proteins, as compared to the control protein. The imprinting
beads had quick adsorption rate and possessed improved regeneration property in comparison with
those prepared directly via inverse-phase suspension polymerization. They consider the formation of
multiple hydrogen bonds and complementary shape between the imprinting cavities and the template
proteins are the two factors that lead to the imprinting effect.
15. Int. J. Mol. Sci. 2006, 7 169
A MIP that uses a stable isotope labeled compound as the template molecule, the so-called IMIP,
was developed by suspension polymerization [68]. The selectivity factors of MIP and IMIP for
bisphenol A (BPA) were 4.45 and 4.43, respectively. Therefore, IMIP was found to have the same
molecular recognition ability as MIP. When MI-SPE with IMIP was used and followed by LC–MS in
the analysis of river water sample, the detection limit of BPA was 1 ppt with high sensitivity.
5.4. Precipitation Polymerization
MIP microspherical shapes with more uniform size can be obtained by the method of precipitation
polymerization, which offers a higher active surface area by manipulating its compositions. As regards
precipitation polymerization, this technique involves coagulation of nano-gel beads followed by
ordered particle growth due to capture of oligomers from surrounding solution [69-70]. In this manner,
near-monodispersed spherical beads can be prepared, and size and porosity can be fine-tuned thereby
changing the polymerization conditions. This technique has been reported in MIP-based competition
assays [71-72] and capillary electrochromatography [73-74], but only recently works have been
published, in which it is clearly shown that precipitation polymerization can be a potentially fruitful
technique for preparing chromatography-grade molecularly imprinted beads [75].
Recently, precipitation polymerization has been employed for the production of molecularly
imprinted microspheres by Ye and Puoci et al [76-78]. Despite the higher yields, a large amount of
template molecules is needed for the preparation process, because of the high dilution factor. The
feasibility of preparing highly selective morphine imprinting polymer particles using precipitation
polymerization is demonstrated by Ho et al. [79]. Since the template, morphine hydrochloride, is dilute
in the polymerization solution, it is assumed that the pH effect can be neglected in the system. The
MIP prepared by precipitation polymerization gave uniform particles, and this proved to be a feasible
method for fabricating MIP. By controlling the separation point during the cross-linking
polymerization process, starting with a dilute monomer solution, uniform molecular imprinted
microspheres were obtained in good yield. Compared with the traditional method, these particles
exhibit greater recognition binding ability in the sensing of morphine without a time-consuming
process of grinding and sieving. The rebinding of MIP by the precipitation polymerization in a
solution containing morphine exhibited better performance than that of NMIP.
Baggiani [80] prepare near monodispersed polystyrene beads by precipitation polymerization in
acetonitrile, and these polymeric beads cheap and easy-to-make, represent a convenient alternative to
the expensive chromatography-grade silica in the iniferter-mediated grafting of MIP. The
chromatographic behaviour of a column packed with these imprinted beads was compared with
another column packed with irregular particles obtained by grinding of a bulk pyrimethanil-imprinted
polymer. These results are consistent with an influence of the polymerization method on the
morphology of the resulting polymer and not on the molecular recognition properties due to the
molecular imprinting process.
16. Int. J. Mol. Sci. 2006, 7 170
5.5. Surface Imprinting Polymerization
Surface grafting of MIP layers onto preformed beads has been recently proposed as attractive and
apparently general techniques to obtain chromatography-grade imprinted materials. In this method,
thin imprinted layers have been successfully used as coatings on chromatography-grade porous silica
using several techniques to restrain the radical polymerization at the surface of the beads [81-82].
An imprinted layer selective to specific molecules on the surface of widely used polymers without
affecting the bulk features was prepared by Sreenivasan [83]. The methodology is simple and modified
surface could be used in applications as diverse as separation, sensing, medical uses, etc. Say et al. [84]
prepared phosphorotriesterase mimic surface imprinted polymeric microbeads using MAH–Cu(II) as a
new metal–chelating monomer. The paraoxon hydrolytic activity results showed that hydrolytic
activity of PIBs was higher than NIBs. The preparation of the polymer is simple, inexpensive and
results demonstrated that the catalytic activity of microbeads has decreased by only 17% after several
uses.
The surface imprinting technique utilizing water-in-oil (W/O) emulsions was applied to the
preparation of a metal ion-imprinted membrane by Araki [85]. The zinc(II) ionimprinted membrane
was successfully prepared by emulsion polymerization with
1,12-dodecanediol-O,O’-diphenylphosphonic acid (functional host molecule), l-glutamic acid
dioleylester ribitol (emulsion stabilizer), and divinylbenzene (polymer matrix-forming monomer). To
obtain flexible and mechanically stable membranes for practical applications, the polymerization was
conducted in the presence of acrylonitrile-butadiene rubber and hydrophilized poly(tetrafluoroethylene)
membranes. The use of acrylonitrile-butadiene rubber and a porous solid support in the polymer
matrix resulted in improved flexibility and mechanical strength of the imprinted membrane. The
permeation mechanism of the metal ions was considered to be hopping of metal ions on the binding
sites in the membranes.
Piacham et al. [86] prepare ultra-thin MIP films using surface initiated radical polymerization.
Polymer films are directly formed on gold-coated quartz crystal resonator, which offers easy
monitoring of polymer growth. With this approach its easy control the thickness of the MIP film to be
below 50 nm, where the selective recognition of target analytes can be easily detected by the
underlying quartz crystal resonator. When used in a flow injection analysis system, the assembled
QCM sensor generated a large frequency change (>30 Hz) upon encountering a small amount of
analyte (0.19 mM). The sensor had a very short response time (<1 min), and displayed certain chiral
selectivity towards the original template, (S)-propranolol at a concentration higher than 0.38mM in
aqueous solution.
5.6. Monolithic Imprinted Polymerization
Monolithic molecularly imprinted technology combined the advantage of monolithic column and
molecular imprinted technology, which was prepared by a simple, one-step, in-situ, free-radical
polymerization ‘‘molding’’ process directly within a chromatographic column without the tedious
17. Int. J. Mol. Sci. 2006, 7 171
procedures of grinding, sieving, and column packing. Monolithic MIP is expected to improve the
separation and enable direct analysis with high-speed and high performance after in–situ
polymerization. Matsui et al. [87-88] first used the in-situ polymerization technique for preparation of
molecularly imprinted monoliths. Template, functional monomer, cross-linker and initiator were
dissolved in mixture porogenic solvents (cyclohexanol and 1-dodecanol) and the mixture was
degassed and poured into a stainless steel column. After polymerization, the template and porogenic
solvents were removed by exhaustive washing with methanol-acetic acid. The monolithic molecularly
imprinted technology has attracted significant interest because of their ease of preparation, high
reproducibility, high selectivity and sensitivity, and rapid mass transport. Furthermore, the preparation
of this type of MIP is more cost-efficient, because the amount of template molecules required is much
lower. Moreover, their greater porosity, and hence good permeability, and high surface area are well
suited for both small molecules and large biopolymers. Monolithic molecularly imprinted stationary
phases have become a rapidly expanding field in chromatographic stationary phase preparation in
recent years [89].
The proportion of mixture composition and polymerization temperature defines the monolithic
structure and separation characteristic without further processing. The key to successful column
preparation of MIP monolith is both choice of the composition of the pre-polymerization mixture and
porogenic solvents and careful timing of the polymerization reaction. In order to compare the different
polymerization methods, Mayes et al. [90] prepared three types of MIP by bulk, multistep-swelling
and grafting methods when some β-blockers were used as the template molecules. In that study,
ground monolithic imprinted polymer was thought to be the best all-round performer for enantiomeric
separations of drugs by HPLC. In-situ polymerization has similar recognition ability and possesses the
advantages of a one-step preparation procedure and high yield. Matsui and Huang [91-93] prepared a
set of monolithic molecularly imprinted polymers with cinchonine and amino acid derivatives as the
template molecules. Separation of the corresponding enantiomers was achieved but the separation
mechanism was not mentioned. In recent years, the uses of monolithic media for superior
chromatographic separation in high-performance liquid chromatography and capillary
electrochromatography have attracted considerable attention [94-102].
Imprinted monolithic membranes by polymerizing mixtures of methacrylic acid and dimethacrylate
crosslinkers within microporous support of filtered paper is described by Kiełczynski [103]. These
membranes are selectively permeable for template molecules but transport of others species is mostly
limited. The measured transport stereoselectivity varied from 1.1 to 3.7 depending on the system used
and the presence of cinchonine in the monomer mixture made membrane more permeable while
cinchonidine reduced its permeability. Optimization of the imprinted polymer membrane in terms of
the number of binding sites and their selectivity for the template enantiomer ought to be connected
with optimization of membrane porosity and template interactions with functional groups. When
EDMA and EDMA:MAA monolithic membranes behave in the predicable way, i.e. transport of
cinchona alkaloids follows membrane templating, TEGDMA-family membranes show abnormal
preference to transport cinchonidine more effectively.
18. Int. J. Mol. Sci. 2006, 7 172
6. Conclusion and Future Outlook
Molecular imprinting, as a technique for the creation of artificial receptor-like binding sites with a
‘‘memory’’ for the shape and functional group positions of the template molecule, has become
increasingly attractive in many fields of analytical chemistry in recent years. However, there are still
many formidable tasks remaining to be tackled. One particular goal is to be able to prepare
molecularly imprinted polymers with a homogeneous population of binding sites, similar to
monoclonal antibodies. New synthesis method with more simplicity and higher selectivity is another
main goal. Improved performance of polymers in aqueous systems, quantitative analysis real samples
and imprinted for large biomolecules are also desirable. Molecular imprinting technology is now
generating increasing industrial interest, and there is a demand for commercially relevant applications.
Molecular imprinting technology not only the principles have to be demonstrated, but their
applicability to the ‘real world’ has also to be shown in the future.
Acknowledgments
The authors gratefully appreciate the financial support by the Center for Advanced Bioseparation
Technology of Inha University, Korea.
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