This document summarizes a study on anion binding by short, flexible aryl triazole oligomers. The study determined binding affinities for various combinations of oligomer and anion using 1H NMR titrations. Effective ionic radius was found to be a primary determinant of relative binding interactions, with small deviations for nonspherical anions. Solvent effects were also significant, with binding strength dependent on solvent donor ability. The results provide insight into anion binding by flexible versus rigid hosts containing electropositive triazole protons.
This document discusses a theoretical study using density functional theory to examine molecular interactions in imidazolium and pyridinium based ionic liquids. Specifically, it optimizes the structures of 1-hexyl- and 1-octyl- substituted 3-methylimidazolium, -pyridinium, and 4-methylpyridinium cations paired with chloride or bromide anions. It then analyzes the interactions between cation and anion through hydrogen bonding, charge distributions, vibrational frequencies, and the impact of hydration through addition of water molecules. The goal is to understand how these interactions influence properties and spectral characteristics at the molecular level.
This document summarizes research on substituent control of hydrogen bonding in palladium(II)-pyrazole complexes. Seven chelate complexes examined via X-ray crystallography all showed intramolecular hydrogen bonding between the pyrazole N-H group and a cis chloride ligand. Intermolecular hydrogen bonding was also observed and could be controlled by the substituent at the C-5 position of pyrazole; complexes with a methyl or no C-5 substituent showed significant intermolecular bonding, while a tert-butyl group at C-5 avoided such bonding. The acidity of two complexes in acetonitrile was estimated to be closer to that of pyridinium ion than imidazol
This document summarizes a study that investigated chromium-citrate and ferric-citrate complexes in aqueous solutions through potentiometric titration experiments. Specifically:
- Potentiometric titration curves showed inflection points, indicating the presence of dominant species for the Cr3+-citrate system. Analysis of the curves suggests the dominant species is a dimeric Cr3+-citrate complex.
- Speciation diagrams for the free citrate ligand agree with literature values. Ferric-citrate and Cr3+-citrate stability constants from literature also support dimer formation.
- The iron-citrate and chromium-citrate systems behaved similarly, both favoring dimeric metal-citrate complexes
Rotaxanes are supramolecular assemblies consisting of a macrocyclic molecule threaded onto a linear molecule capped with bulky stoppers. They can be synthesized through template-directed methods like clipping, threading, and snapping. Switchable rotaxanes have applications in logic gates and memory due to their ability to shuttle between binding stations. Rotaxanes can also be used to enhance or reduce reactivity, act as molecular muscles, and self-assemble into structures that can slowly release dye.
This document provides an overview of supramolecular chemistry. It begins with a brief history and definitions of key terms like supramolecular chemistry and self-assembly. It then describes various types of non-covalent interactions that hold supramolecular structures together, such as hydrogen bonding, metal-ligand interactions, π-π stacking, and hydrophobic effects. Examples are given of self-assembled structures like grids, helicates, and polyhedral cages. The document concludes by noting the increasing sophistication of supramolecular systems incorporating components like fullerenes and nanoparticles for applications in nanotechnology.
This document discusses supramolecular polymers, which are polymeric arrays brought together by non-covalent interactions like hydrogen bonding, metal coordination, and π-π stacking. It provides examples of hydrogen bonding between molecules like PEG and methyl isocytosine, and metal coordination involving ligands. Supramolecular polymers can be synthesized through reactions like one producing a quadruple hydrogen bond supramolecular polymer from PEG and MIC, with characteristics analyzed using techniques like FTIR, UV-Vis, NMR, and DSC.
This document discusses the various energy components that contribute to intermolecular non-covalent interactions. It describes the main energy components as: electrostatic energy, exchange repulsion energy, polarization energy, charge transfer energy, and dispersion attraction. Electrostatic energy is the longest-ranging and depends on molecular moments. Exchange repulsion prevents electron overlap between molecules. Polarization energy arises from charge redistribution when molecules interact. Charge transfer involves small amounts of electron transfer between interacting molecules. Dispersion attraction exists for all atom pairs and is the sole interaction for rare gases. The individual energies are weak but can add up significantly in molecular environments like binding interactions.
This document discusses a theoretical study using density functional theory to examine molecular interactions in imidazolium and pyridinium based ionic liquids. Specifically, it optimizes the structures of 1-hexyl- and 1-octyl- substituted 3-methylimidazolium, -pyridinium, and 4-methylpyridinium cations paired with chloride or bromide anions. It then analyzes the interactions between cation and anion through hydrogen bonding, charge distributions, vibrational frequencies, and the impact of hydration through addition of water molecules. The goal is to understand how these interactions influence properties and spectral characteristics at the molecular level.
This document summarizes research on substituent control of hydrogen bonding in palladium(II)-pyrazole complexes. Seven chelate complexes examined via X-ray crystallography all showed intramolecular hydrogen bonding between the pyrazole N-H group and a cis chloride ligand. Intermolecular hydrogen bonding was also observed and could be controlled by the substituent at the C-5 position of pyrazole; complexes with a methyl or no C-5 substituent showed significant intermolecular bonding, while a tert-butyl group at C-5 avoided such bonding. The acidity of two complexes in acetonitrile was estimated to be closer to that of pyridinium ion than imidazol
This document summarizes a study that investigated chromium-citrate and ferric-citrate complexes in aqueous solutions through potentiometric titration experiments. Specifically:
- Potentiometric titration curves showed inflection points, indicating the presence of dominant species for the Cr3+-citrate system. Analysis of the curves suggests the dominant species is a dimeric Cr3+-citrate complex.
- Speciation diagrams for the free citrate ligand agree with literature values. Ferric-citrate and Cr3+-citrate stability constants from literature also support dimer formation.
- The iron-citrate and chromium-citrate systems behaved similarly, both favoring dimeric metal-citrate complexes
Rotaxanes are supramolecular assemblies consisting of a macrocyclic molecule threaded onto a linear molecule capped with bulky stoppers. They can be synthesized through template-directed methods like clipping, threading, and snapping. Switchable rotaxanes have applications in logic gates and memory due to their ability to shuttle between binding stations. Rotaxanes can also be used to enhance or reduce reactivity, act as molecular muscles, and self-assemble into structures that can slowly release dye.
This document provides an overview of supramolecular chemistry. It begins with a brief history and definitions of key terms like supramolecular chemistry and self-assembly. It then describes various types of non-covalent interactions that hold supramolecular structures together, such as hydrogen bonding, metal-ligand interactions, π-π stacking, and hydrophobic effects. Examples are given of self-assembled structures like grids, helicates, and polyhedral cages. The document concludes by noting the increasing sophistication of supramolecular systems incorporating components like fullerenes and nanoparticles for applications in nanotechnology.
This document discusses supramolecular polymers, which are polymeric arrays brought together by non-covalent interactions like hydrogen bonding, metal coordination, and π-π stacking. It provides examples of hydrogen bonding between molecules like PEG and methyl isocytosine, and metal coordination involving ligands. Supramolecular polymers can be synthesized through reactions like one producing a quadruple hydrogen bond supramolecular polymer from PEG and MIC, with characteristics analyzed using techniques like FTIR, UV-Vis, NMR, and DSC.
This document discusses the various energy components that contribute to intermolecular non-covalent interactions. It describes the main energy components as: electrostatic energy, exchange repulsion energy, polarization energy, charge transfer energy, and dispersion attraction. Electrostatic energy is the longest-ranging and depends on molecular moments. Exchange repulsion prevents electron overlap between molecules. Polarization energy arises from charge redistribution when molecules interact. Charge transfer involves small amounts of electron transfer between interacting molecules. Dispersion attraction exists for all atom pairs and is the sole interaction for rare gases. The individual energies are weak but can add up significantly in molecular environments like binding interactions.
This document summarizes a study that used X-ray crystallography and resonance Raman spectroscopy to characterize the oxo-molybdenum dithiolene complex (Tp*)MoO(qdt), which is a model system relevant to pyranopterin molybdenum enzyme active sites like sulfite oxidase. The compound was found to crystallize in the triclinic space group P1. Structural parameters of the first coordination sphere were similar to the related complex (Tp*)MoO(bdt), suggesting geometric effects are not major contributors to electronic structural differences between the two complexes. Raman spectroscopy provided evidence the dithiolene ligand interacts with the molybdenum center through
The document discusses developing novel fluorescent dyes through asymmetric boron difluoride complexes. It aims to design dyes with broad Stokes shifts like BODIPY but without its narrow emission properties. Future work discussed includes synthesizing BF2 complexes with N,O and N,N ligands to study the effect of heteroatomic substitution on emission. Distyryl and arylbenzamide BF2 complexes will also be made to investigate conjugation extension and solid state quenching effects. The overall goal is tunable dyes for applications like bioimaging, sensors and light emitting devices.
Saturation of ions in channels and solutions a Fermi-Poisson treatment 11-23-...Bob Eisenberg
Ions in water, and in and near channels, proteins, nucleic acids, and electrodes are difficult to analyze, because everything interacts with everything else through the electric field and through the steric exclusion of ions and water. Ions and water have their own space and cannot overlap significantly. Excluded volume has almost always been treated by enforcing force laws that prevent overlap. Such treatments are difficult to compute because of the singularity of the forces and the need for three dimensions. Here we take a different approach and enforce a Fermi like distribution of the entropy of mixtures of spheres of any size, derived by J.-L. Liu. We show that this approach fits the complex properties of calcium channels, and the properties of gramicdin channels, computed from their full three dimensional structure. Using the simplest shell treatment of hydration, we successfully compute the activity (free energy per mole) curves of pure calcium and sodium chloride solutions. The Fermi-Poisson approach uses the full consistency of its mathematics to replace the computation of repulsive forces. It may prove to be good enough to detail with experimental data in three dimensions difficult to deal with accurately in any other way.
A non-covalent interaction differs from a covalent bond in that it does not involve the sharing of electrons, but rather involves more dispersed variations of electromagnetic interactions between molecules or within a molecule.
The document summarizes research tuning the redox properties of BODIPY dyes through substituent manipulation. The goals were to create a method to predict BODIPY redox potentials using linear free energy relationships relating substituent Hammett parameters to reduction/oxidation potentials. Various BODIPY dyes with different substituents were synthesized, characterized through cyclic voltammetry, and fitted to equations relating electrochemical values to Hammett coefficients to achieve the goals.
1. Non-covalent interactions like electrostatic interactions, hydrogen bonds, van der Waals forces, and hydrophobic interactions play important roles in stabilizing macromolecular structures like proteins.
2. These interactions are weak but numerous, allowing for spontaneous assembly of larger structures. They also allow conformational changes important for biochemical functions while maintaining overall structure.
3. Electrostatic interactions depend on distance between charges and the dielectric constant of the medium, with an optimal distance of around 2.8 Angstroms. Hydrogen bonds are weaker than covalent bonds but important in structures. Van der Waals forces and hydrophobic interactions also contribute to stability.
This document discusses various types of non-covalent interactions including van der Waals forces, hydrogen bonding, electrostatic interactions, and hydrophobic interactions. It provides details on the relative strengths of each interaction and their importance in maintaining the structure of biological molecules like proteins and nucleic acids. Specific examples highlighted include hydrogen bonding holding together the DNA double helix and hydrophobic interactions driving the association of nonpolar molecules in aqueous solutions.
This document discusses the influence of various factors on counterion condensation in aqueous solutions of sodium polystyrenesulfonate polyelectrolyte. Electrical conductivity measurements were used to analyze the interactions between the polyion and counterions. The extent of counterion condensation was found to be affected by the polyelectrolyte concentration and molecular weight, added electrolyte concentration, and temperature. The results provide insight into how polyelectrolyte molecular weight influences counterion condensation behavior in the presence of added electrolytes.
This course provides an in-depth understanding of three-dimensional macromolecular structure and the relationship between the conformation of proteins and nucleic acids and their biological functions. Students will learn to visualize and analyze macromolecular structures using molecular graphics software and assess the structural basis of biological activity. The course covers topics related to multi-molecular assemblies, catalytic machines, and membrane proteins. Students will be assessed through a final exam and computer graphics exercises completed in a lab notebook.
Supramolecular chemistry is the chemistry of intermolecular bonds between two or more chemical species. It was pioneered in the late 19th century and Nobel Prizes have been awarded for its development. Supramolecular interactions include ion-ion, ion-dipole, and dipole-dipole interactions. Building blocks include macrocycles, structural units, and biologically derived units. Control relies on thermodynamics and the molecular environment. Applications include materials technology, catalysis, medicine, and other devices. Intensive research is enabling new functional materials and more effective catalysis through template-directed synthesis.
Electrolyte Solutions for Rechargeable Li-Ion Batteries Based on Fluorinated ...AMAL THOMAS
High voltage lithium ion batteries have been a focus in the current energy storage research due to their
potential application as high energy density batteries for electric vehicles. With more energy stored in
a system with the same weight and volume, the impact of battery fabrication and its utilization on the
environment will be minimized .Electrolyte solutions based on fluorinated solvents were studied in
high-voltage Li-ion cells using lithium as the anode has a great enhancement over conventional
electrolyte and Li1.2Mn0.56Co0.08Ni0.16O2 as the cathode provides excellent voltage stability on the 5.0
V at both ambient and elevated temperatures. Performance can be reach peak by replacing convectional
alky carbonate solvents in electrolyte solution by fluorinated cosolvents. Fluorinated electrolyte
solution act as a buffering surface film which is highly reactive electrophilic alkyl carbonates, from
continuous detrimental reactions with solution species. Excellent cyclic performance was recorded in
solution containing fluorinated solvents. The extraordinary electrochemical stability of this electrolyte
solution makes it a suitable candidate for other high-voltage cathode materials.
Polyphosphazenes... preparation and properties by Dr. Salma Amirsalmaamir2
This document discusses inorganic polymers called polyphosphazenes. It describes their general molecular structure as having an alternating phosphorus and nitrogen backbone with two organic side groups attached to each phosphorus atom. Over 700 types of polyphosphazenes have been synthesized with a wide range of physical and chemical properties. They are synthesized via ring opening polymerization or condensation polymerization of monomers. Polyphosphazenes have properties including flexibility, solubility, elasticity, and degradation rates that depend on the specific organic side groups. They can be modified and crosslinked for different applications.
One pot synthesis of cu(ii) 2,2′ bipyridyl complexes of 5-hydroxy-hydurilic acidrkkoiri
This document describes the one-pot synthesis of two new copper(II) complexes containing the ligands 5-hydroxy-hydurilic acid (complex 1) and alloxanic acid (complex 2) from the reaction of a barbiturate derivative (LH4) with Cu(II) 2,2'-bipyridyl complexes. It also reports the synthesis of a third complex (complex 3) from the reaction of LH4 with copper nitrate that retains the ligand framework. The complexes were characterized using X-ray crystallography, spectroscopy, and electrochemistry. Complexes 1 and 3 were found to cleave DNA and showed cytotoxic activity against cancer cells, while complex 2 was insoluble and not
This document describes the design, synthesis, and evaluation of a series of 1,3-disubstituted pyrrolo[2,3-b]quinoxalines as potential inhibitors of phosphodiesterase 4 (PDE4) and cancer cell growth. A ligand- and phase transfer catalyst-free intramolecular Heck reaction was used to synthesize the target compounds. Some compounds showed significant inhibition of PDE4B and growth inhibition of oral cancer cells in vitro. They also showed acceptable safety profiles in zebrafish embryos, but no apoptosis was observed. The goal was to develop PDE4 inhibitors that do not inhibit luciferase, which could produce false positives in assays.
- The document studies using water as an alternative solvent to the commonly used acetonitrile for applying organic layers from diazonium salts.
- When using water, the diazonium salt solution had to be replaced every couple days to maintain a consistent concentration, as the salt decomposed over time, turning the solution orange.
- Preliminary results found that layers could be applied using water as a solvent, but it may lack control over completeness of the layer compared to acetonitrile.
This document discusses the history and key concepts of supramolecular chemistry. It describes supramolecular chemistry as the study of intermolecular interactions and self-assembly of molecules into higher order structures. It notes that supramolecular systems act as a bridge between living and non-living matter. The document also outlines different ways of studying supramolecular systems, such as investigating synthetic or natural systems. It provides examples of applications like sensing, drug delivery, and molecular imaging.
This document reports on the synthesis and characterization of polyethyleneimine-anchored copper(II) complexes and their in vitro DNA binding studies and cytotoxicity. Specifically, it synthesized copper(II) complexes containing 1,10-phenanthroline and L-tyrosine ligands bound to a branched polyethyleneimine polymer. It characterized the complexes using various techniques and studied their binding to calf thymus DNA. It found that the complex with the highest degree of copper(II) coordination bound most strongly to DNA. Finally, it evaluated the cytotoxic activity of this complex against MCF-7 breast cancer cells.
This document summarizes a study that determined the self-exchange electron transfer rate constant for the vanadium(IV/V) couple in the natural product amavadin. Key findings include:
1) The self-exchange rate constant for amavadin was determined to be 1 x 106 dm3 mol-1 s-1 at 25°C, representing the first unambiguous example for a vanadium(IV/V) couple.
2) Amavadin's structure, with an eight-coordinate non-oxo vanadium center and lack of "yl" type oxygens, allows unambiguous determination of the self-exchange rate constant without complications from other pathways or geometry changes.
3) Direct measurement using
Roman Boulatov and colleagues developed a new approach to force spectroscopy using small molecule probes to apply mechanical forces to reactive groups and study chemomechanical phenomena. They designed a cyclic molecule, stilbene, that can be switched between a relatively unstrained and highly strained state using light, applying forces in the range of tens to hundreds of piconewtons. They observed the rate of dissociation of a carbon-carbon bond increase by a factor of 106 under the highest forces. This new approach miniaturizes force spectroscopy to the nanoscale and allows reactions to be monitored using conventional spectroscopy tools, providing insights into mechanically assisted chemistry not visible to other methods.
This document summarizes a study of electron transfer reactions of the eight-coordinate vanadium complex bis-(N-hydroxyiminodiacetate)vanadium(IV) [V(HIDA)2]2–, which is a synthetic analog of the natural compound amavadin found in mushrooms. The self-exchange rate constant of the [V(HIDA)2]2–/– redox couple was determined using both Marcus theory calculations from oxidation/reduction cross reactions, and direct measurement using 51V NMR line broadening techniques. The average self-exchange rate constant was found to be 1.5 × 105 M–1 s–1, similar to that of amavadin itself. This suggests that
This document summarizes a study that used X-ray crystallography and resonance Raman spectroscopy to characterize the oxo-molybdenum dithiolene complex (Tp*)MoO(qdt), which is a model system relevant to pyranopterin molybdenum enzyme active sites like sulfite oxidase. The compound was found to crystallize in the triclinic space group P1. Structural parameters of the first coordination sphere were similar to the related complex (Tp*)MoO(bdt), suggesting geometric effects are not major contributors to electronic structural differences between the two complexes. Raman spectroscopy provided evidence the dithiolene ligand interacts with the molybdenum center through
The document discusses developing novel fluorescent dyes through asymmetric boron difluoride complexes. It aims to design dyes with broad Stokes shifts like BODIPY but without its narrow emission properties. Future work discussed includes synthesizing BF2 complexes with N,O and N,N ligands to study the effect of heteroatomic substitution on emission. Distyryl and arylbenzamide BF2 complexes will also be made to investigate conjugation extension and solid state quenching effects. The overall goal is tunable dyes for applications like bioimaging, sensors and light emitting devices.
Saturation of ions in channels and solutions a Fermi-Poisson treatment 11-23-...Bob Eisenberg
Ions in water, and in and near channels, proteins, nucleic acids, and electrodes are difficult to analyze, because everything interacts with everything else through the electric field and through the steric exclusion of ions and water. Ions and water have their own space and cannot overlap significantly. Excluded volume has almost always been treated by enforcing force laws that prevent overlap. Such treatments are difficult to compute because of the singularity of the forces and the need for three dimensions. Here we take a different approach and enforce a Fermi like distribution of the entropy of mixtures of spheres of any size, derived by J.-L. Liu. We show that this approach fits the complex properties of calcium channels, and the properties of gramicdin channels, computed from their full three dimensional structure. Using the simplest shell treatment of hydration, we successfully compute the activity (free energy per mole) curves of pure calcium and sodium chloride solutions. The Fermi-Poisson approach uses the full consistency of its mathematics to replace the computation of repulsive forces. It may prove to be good enough to detail with experimental data in three dimensions difficult to deal with accurately in any other way.
A non-covalent interaction differs from a covalent bond in that it does not involve the sharing of electrons, but rather involves more dispersed variations of electromagnetic interactions between molecules or within a molecule.
The document summarizes research tuning the redox properties of BODIPY dyes through substituent manipulation. The goals were to create a method to predict BODIPY redox potentials using linear free energy relationships relating substituent Hammett parameters to reduction/oxidation potentials. Various BODIPY dyes with different substituents were synthesized, characterized through cyclic voltammetry, and fitted to equations relating electrochemical values to Hammett coefficients to achieve the goals.
1. Non-covalent interactions like electrostatic interactions, hydrogen bonds, van der Waals forces, and hydrophobic interactions play important roles in stabilizing macromolecular structures like proteins.
2. These interactions are weak but numerous, allowing for spontaneous assembly of larger structures. They also allow conformational changes important for biochemical functions while maintaining overall structure.
3. Electrostatic interactions depend on distance between charges and the dielectric constant of the medium, with an optimal distance of around 2.8 Angstroms. Hydrogen bonds are weaker than covalent bonds but important in structures. Van der Waals forces and hydrophobic interactions also contribute to stability.
This document discusses various types of non-covalent interactions including van der Waals forces, hydrogen bonding, electrostatic interactions, and hydrophobic interactions. It provides details on the relative strengths of each interaction and their importance in maintaining the structure of biological molecules like proteins and nucleic acids. Specific examples highlighted include hydrogen bonding holding together the DNA double helix and hydrophobic interactions driving the association of nonpolar molecules in aqueous solutions.
This document discusses the influence of various factors on counterion condensation in aqueous solutions of sodium polystyrenesulfonate polyelectrolyte. Electrical conductivity measurements were used to analyze the interactions between the polyion and counterions. The extent of counterion condensation was found to be affected by the polyelectrolyte concentration and molecular weight, added electrolyte concentration, and temperature. The results provide insight into how polyelectrolyte molecular weight influences counterion condensation behavior in the presence of added electrolytes.
This course provides an in-depth understanding of three-dimensional macromolecular structure and the relationship between the conformation of proteins and nucleic acids and their biological functions. Students will learn to visualize and analyze macromolecular structures using molecular graphics software and assess the structural basis of biological activity. The course covers topics related to multi-molecular assemblies, catalytic machines, and membrane proteins. Students will be assessed through a final exam and computer graphics exercises completed in a lab notebook.
Supramolecular chemistry is the chemistry of intermolecular bonds between two or more chemical species. It was pioneered in the late 19th century and Nobel Prizes have been awarded for its development. Supramolecular interactions include ion-ion, ion-dipole, and dipole-dipole interactions. Building blocks include macrocycles, structural units, and biologically derived units. Control relies on thermodynamics and the molecular environment. Applications include materials technology, catalysis, medicine, and other devices. Intensive research is enabling new functional materials and more effective catalysis through template-directed synthesis.
Electrolyte Solutions for Rechargeable Li-Ion Batteries Based on Fluorinated ...AMAL THOMAS
High voltage lithium ion batteries have been a focus in the current energy storage research due to their
potential application as high energy density batteries for electric vehicles. With more energy stored in
a system with the same weight and volume, the impact of battery fabrication and its utilization on the
environment will be minimized .Electrolyte solutions based on fluorinated solvents were studied in
high-voltage Li-ion cells using lithium as the anode has a great enhancement over conventional
electrolyte and Li1.2Mn0.56Co0.08Ni0.16O2 as the cathode provides excellent voltage stability on the 5.0
V at both ambient and elevated temperatures. Performance can be reach peak by replacing convectional
alky carbonate solvents in electrolyte solution by fluorinated cosolvents. Fluorinated electrolyte
solution act as a buffering surface film which is highly reactive electrophilic alkyl carbonates, from
continuous detrimental reactions with solution species. Excellent cyclic performance was recorded in
solution containing fluorinated solvents. The extraordinary electrochemical stability of this electrolyte
solution makes it a suitable candidate for other high-voltage cathode materials.
Polyphosphazenes... preparation and properties by Dr. Salma Amirsalmaamir2
This document discusses inorganic polymers called polyphosphazenes. It describes their general molecular structure as having an alternating phosphorus and nitrogen backbone with two organic side groups attached to each phosphorus atom. Over 700 types of polyphosphazenes have been synthesized with a wide range of physical and chemical properties. They are synthesized via ring opening polymerization or condensation polymerization of monomers. Polyphosphazenes have properties including flexibility, solubility, elasticity, and degradation rates that depend on the specific organic side groups. They can be modified and crosslinked for different applications.
One pot synthesis of cu(ii) 2,2′ bipyridyl complexes of 5-hydroxy-hydurilic acidrkkoiri
This document describes the one-pot synthesis of two new copper(II) complexes containing the ligands 5-hydroxy-hydurilic acid (complex 1) and alloxanic acid (complex 2) from the reaction of a barbiturate derivative (LH4) with Cu(II) 2,2'-bipyridyl complexes. It also reports the synthesis of a third complex (complex 3) from the reaction of LH4 with copper nitrate that retains the ligand framework. The complexes were characterized using X-ray crystallography, spectroscopy, and electrochemistry. Complexes 1 and 3 were found to cleave DNA and showed cytotoxic activity against cancer cells, while complex 2 was insoluble and not
This document describes the design, synthesis, and evaluation of a series of 1,3-disubstituted pyrrolo[2,3-b]quinoxalines as potential inhibitors of phosphodiesterase 4 (PDE4) and cancer cell growth. A ligand- and phase transfer catalyst-free intramolecular Heck reaction was used to synthesize the target compounds. Some compounds showed significant inhibition of PDE4B and growth inhibition of oral cancer cells in vitro. They also showed acceptable safety profiles in zebrafish embryos, but no apoptosis was observed. The goal was to develop PDE4 inhibitors that do not inhibit luciferase, which could produce false positives in assays.
- The document studies using water as an alternative solvent to the commonly used acetonitrile for applying organic layers from diazonium salts.
- When using water, the diazonium salt solution had to be replaced every couple days to maintain a consistent concentration, as the salt decomposed over time, turning the solution orange.
- Preliminary results found that layers could be applied using water as a solvent, but it may lack control over completeness of the layer compared to acetonitrile.
This document discusses the history and key concepts of supramolecular chemistry. It describes supramolecular chemistry as the study of intermolecular interactions and self-assembly of molecules into higher order structures. It notes that supramolecular systems act as a bridge between living and non-living matter. The document also outlines different ways of studying supramolecular systems, such as investigating synthetic or natural systems. It provides examples of applications like sensing, drug delivery, and molecular imaging.
This document reports on the synthesis and characterization of polyethyleneimine-anchored copper(II) complexes and their in vitro DNA binding studies and cytotoxicity. Specifically, it synthesized copper(II) complexes containing 1,10-phenanthroline and L-tyrosine ligands bound to a branched polyethyleneimine polymer. It characterized the complexes using various techniques and studied their binding to calf thymus DNA. It found that the complex with the highest degree of copper(II) coordination bound most strongly to DNA. Finally, it evaluated the cytotoxic activity of this complex against MCF-7 breast cancer cells.
This document summarizes a study that determined the self-exchange electron transfer rate constant for the vanadium(IV/V) couple in the natural product amavadin. Key findings include:
1) The self-exchange rate constant for amavadin was determined to be 1 x 106 dm3 mol-1 s-1 at 25°C, representing the first unambiguous example for a vanadium(IV/V) couple.
2) Amavadin's structure, with an eight-coordinate non-oxo vanadium center and lack of "yl" type oxygens, allows unambiguous determination of the self-exchange rate constant without complications from other pathways or geometry changes.
3) Direct measurement using
Roman Boulatov and colleagues developed a new approach to force spectroscopy using small molecule probes to apply mechanical forces to reactive groups and study chemomechanical phenomena. They designed a cyclic molecule, stilbene, that can be switched between a relatively unstrained and highly strained state using light, applying forces in the range of tens to hundreds of piconewtons. They observed the rate of dissociation of a carbon-carbon bond increase by a factor of 106 under the highest forces. This new approach miniaturizes force spectroscopy to the nanoscale and allows reactions to be monitored using conventional spectroscopy tools, providing insights into mechanically assisted chemistry not visible to other methods.
This document summarizes a study of electron transfer reactions of the eight-coordinate vanadium complex bis-(N-hydroxyiminodiacetate)vanadium(IV) [V(HIDA)2]2–, which is a synthetic analog of the natural compound amavadin found in mushrooms. The self-exchange rate constant of the [V(HIDA)2]2–/– redox couple was determined using both Marcus theory calculations from oxidation/reduction cross reactions, and direct measurement using 51V NMR line broadening techniques. The average self-exchange rate constant was found to be 1.5 × 105 M–1 s–1, similar to that of amavadin itself. This suggests that
This document summarizes research on the use of 1,4-diaryl-1,2,3-triazole oligomers as anion receptors. Computer modeling and NMR spectroscopy show that oligomers 1-3 fold into helical structures upon chloride binding, with the electropositive CH groups of the triazoles oriented toward the interior to interact with the anion. Binding constants increase with oligomer length, from 12 m-1 for dimer 2 to over 1,000 m-1 for trimer 3, indicating the multivalent effect of additional triazole units. X-ray crystallography of trimer-chloride complex 3b·Cl- confirms the predicted folded conformation. The results demonstrate that
Gem-dichlorocyclopropanes (gDCCs) incorporated along polybutadiene copolymer backbones undergo mechanically assisted ring-opening reactions when subjected to ultrasound, providing a probe of stress distributions. Over 80% of gDCC rings open while the molecular weight degrades by around 80%, corresponding to an average of 1650 ring openings and 3 chain scission cycles per original polymer chain. The reactivity of cis and trans gDCC units is nearly equivalent, suggesting localized regions of high stress dominate over stereochemical effects. gDCC ring opening is much more frequent than chain scission, allowing extensive mechanochemical remodeling.
This weekly planner template provides a schedule for each day of the week broken into half-hour increments from 7:00 AM to 11:00 PM. The user can fill in planned activities, appointments or other items for each time slot to help organize their week.
The document discusses best practices for libraries to embrace social media and online engagement. It recommends that libraries 1) listen to their communities online, 2) use basic online communication tools like adding pictures and being conversational, and 3) get involved in doing community events with less control and more interaction. The goal is to transform libraries into places that have more face-to-face interactions and connections by being present online.
Learn how to build a better candidate persona with Paul Hebert, contributor to Fistful of Talent and Andre Boulais from Jobvite. They will outline what is a candidate persona and why you need them to improve your recruiting process
With the explosion of the maker movement, schools are beginning to embrace creativity. However, what does this mean for assessment? Should we assess the creative process? Should we assess the finished product? Does assessing creativity actually make kids more risk-averse? In this workshop we explore what it means to assess both the creative process and the creative product without leading to risk aversion.
This document summarizes a study of general trends in the acceptor ability of σ bonds (C-X) where X is a main group element from groups IVa-IIa. The study finds that acceptor ability increases when moving to the end of a period and down a group in monosubstituted ethanes. In monosubstituted ethenes, acceptor ability is more dependent on the electronegativity of the substituent X. C-X bonds can have highly anisotropic stereoelectronic effects, with some bonds being good acceptors at one end but poor at the other. The trends revealed provide a qualitative understanding of stereoelectronic effects, though the magnitude of hyperconjugative
The document summarizes 4 posters presented at a conference.
Poster 1 describes molecular dynamics simulations of the binding of heme-dependent activator YC-1 into the catalytic domain of soluble guanylate cyclase. The simulations revealed a potential binding site between pseudo-symmetric and catalytic sites.
Poster 2 discusses triarylmethyl radicals as potential building blocks for molecular spintronics. Computational studies showed these radicals have relatively high conductivity and magnetoresistance effects suitable for spintronic applications.
Poster 3 examines molecular dynamics simulations of gadolinium-doped ceria and yttria-stabilized zirconia interfaces for solid oxide fuel cell electrolyte applications. The simulations explored oxygen
A stringent limit_on_a_drifting_photon_to_electron_mass_ratio_from_alcohol_in...Sérgio Sacani
This document summarizes a study that uses methanol molecules observed in a distant galaxy to set limits on a possible variation of the proton-to-electron mass ratio over cosmic time scales. The researchers observed four methanol absorption lines in a galaxy with a redshift of 0.88582, corresponding to 7 billion years in the past. They found the measured frequencies of the lines to be consistent with no change in the proton-to-electron mass ratio, setting an upper limit of ∆m/m = (0.0 ± 1.0) × 10-7 over that time period. This stringent limit provides evidence that fundamental constants may not vary significantly over cosmic history.
Influence of the alkyl chain length of alkyltriazoles on the corrosion inhibi...Al Baha University
Abstract. Steel is an important material and has been widely used in today's industrial production. Using organic
corrosion inhibitors is an effective means to prevent steel from corrosion. Generally, the molecular structures of
inhibitors can have a major impact on their corrosion inhibition efficiency. In this work, the influence of alkyl chain
length of three alkyltriazoles on the corrosion inhibition of iron has been investigated by density functional based tight
binding (DFTB) approach. Several typical descriptors such as frontier molecular orbital, adsorption energy, density of
states have been discussed in detail. Our findings will contribute to the understanding of the inhibition mechanism and
the designing of novel corrosion inhibitors.
This document reports on a study of the oxygenation properties of hemoglobin from the earthworm Lumbricus terrestris under varying conditions of pH, salts, and temperature. Key findings include:
1) Hemoglobin from L. terrestris exhibits relatively small cooperativity (free energy of 1.6-2.8 kcal/mol) and a large, pH-dependent Hill coefficient that reaches a maximum of 7.9.
2) Cations, not anions, control oxygen binding, with divalent cations having a larger effect than monovalent cations. Effectiveness decreases in the order Ca2+ > Sr2+ > Ba2+ and Mg2+ > Na+.
Halogen bonding occurs when a halogen acts as a Lewis acid to form close contacts with electron-rich species. It can range from weak to strong depending on factors like the halogen, substituents, and binding site environment. In drug design, halogen bonding has been successfully utilized to improve binding affinity and selectivity by targeting protein binding sites. Consideration of halogen bonding may prove beneficial in developing new drug molecules.
A chemical bond is a lasting attraction between atoms that enables the formation of chemical compounds. The bond may result from the electrostatic force of attraction between atoms with opposite charges, or through the sharing of electrons as in the covalent bonds.
Quantum Mechanical Calculations on Novel Actinide Chelatin.docxamrit47
Quantum Mechanical Calculations on Novel Actinide Chelating Agents
Aisha Mehmood, Maria Benavides, PhD
Department of Natural Sciences
www.uhd.edu/academic/colleges/sciences/ns/
Abstract: Plutonium is produced in significant amounts as the isotope 239Pu during nuclear reactor operations. The use of actinides such as Pu in energy and weapons production has resulted in major environmental and health concerns. In the event of actinide release it is critical to have the means to treat large number of people in a very short time. Chelation therapy is the approach currently used to treat actinide poisoning because it reduces the deposition of actinides in the internal organs. In order to effectively respond and treat actinide poisoning on a massive scale it is crucial to have access to effective, nontoxic chelating agents that can be orally administered, that are easily produced and safely stored at any location. Specific sequestering agents have been designed and synthesized to bind actinides. Our study focuses on determining the structures and molecular properties of four hydroxypyridinone (HOPO)-based sequestering agents 2,2-Dime-3LI(1,2-HOPO), 3LI-(1,2-HOPO), 4LI(1,2-HOPO) and 5LI(1,2-HOPO) which have been shown to strongly and specifically bind plutonium at physiological pH. Our calculations were carried out using density functional theory (DFT) with the B3LYP functional applied in conjunction with three increasingly larger basis sets (3-21G, 6-31G, and 6-311G) to obtain the equilibrium geometries, vibrational frequencies, and IR spectra for all four ligands. The highest occupied molecular orbital (HOMO) – lowest occupied molecular orbital (LUMO) energy gap values for all four compounds are greater than 4 eV suggesting that the ligands are chemically stable. Two hydrogen bonds are observed in each compound which we suspect contribute to their chemical stability. The four compounds exhibit dipole moments ranging between 3 to 4 Debye which indicates they possess polar character. Our computed vibrational frequencies were found in excellent agreement with the experimental frequencies, suggesting our proposed models are good representations of the actual molecular structures.
Introduction: Over the past years concern for harm caused by radiation in human body has increased. Recent disaster such as Fukushima Daiichi nuclear reactor accident in Japan has raised red flags for radiation safety. Such events are not common; however once the damage has happened, it is large and capable of destroying many lives. Nuclear fissions release significant amount of several different actinides that can enter human body through radiation or radioactive substances. All actinides are radioactive and bind with human internal tissue. Chelation therapy has shown positive results for reducing internal human actinide contamination. Plutonium (Pu) is an alpha emitter that is known to have the greatest retention in the human body among actinides. Our studies focuses ...
This study examines lunar basalt sample 10020, which is approximately 3.7 billion years old. Paleomagnetic measurements and petrologic analysis reveal the sample contains a stable natural remanent magnetization acquired in a magnetic field of at least 12 microteslas. This provides evidence the lunar dynamo, which was likely present 4.2 billion years ago, persisted for at least another 500 million years. A long-lived lunar dynamo would have required an energy source beyond secular cooling of the lunar interior. The findings extend knowledge of the lunar dynamo and present a challenge to current dynamo theory.
This document provides an overview of molecular polarity. It defines key terms like electronegativity, polar bonds, and molecular polarity. The objectives are to define electronegativity, distinguish between polar and non-polar molecules, and explain how molecular polarity relates to properties like melting points and solubility. Examples of polar molecules like water and non-polar molecules like nitrogen are given. Bond polarity is determined by differences in electronegativity between atoms, while molecular polarity depends on both bond polarity and molecular geometry.
BUBBLE COALESCENCE INHIBITION IN AQUEOUS ELECTROLYTE SOLUTIONMijul Saxena
This document presents a study on bubble coalescence inhibition in aqueous electrolyte solutions. The study investigated the transition concentrations of single and mixed inorganic electrolytes (CaCl2, NaCl, Na2SO4, MgSO4) that inhibit bubble coalescence. Experiments were conducted in a bubble column by producing pairs of air bubbles in electrolyte solutions and measuring the percentage of bubbles that coalesced. Results showed that all electrolytes inhibited coalescence below a transition concentration, with CaCl2 providing the strongest inhibition. The strength of inhibition for mixed electrolytes followed the combination of the individual electrolytes. The transition concentrations depended on ion type and combination.
Fluoride Recognition of Amide- and Pyrrole-Based Receptors: A Theoretical Study drboon
The novel amide-based receptors, N-(anthracen-1-yl)-1H-pyrrole-2-carboxamide (1) and N-(8-(1H-pyrrole-2-carboxamido) anthracen-1-yl)-1H-pyrrole-2-carboxamide (2) have been designed and investigated for their halide ion recognition using the density functional theory calculations in gas and solvent phases. Electronic and thermodynamic properties of halide ion binding complexes of receptors were investigated. Intermolecular interactions in all the studied complexes occurring via hydrogen bonding are found. The designed receptors 1 and 2 are found to be excellent selectivity for fluoride ion in both gas and solvent phases.
This document summarizes the rational design and generation of a catalytic antibody that selectively hydrolyzes a specific substrate. Researchers designed an antibody to bind a transition state analogue for the hydrolysis of a carbonate substrate. They generated monoclonal antibodies against a nitrophenyl phosphonate transition state analogue. One antibody was found to catalyze the hydrolysis of the carbonate substrate, displaying Michaelis-Menten kinetics. The antibody-catalyzed reaction had substrate specificity and was competitively inhibited by the corresponding phosphate transition state analogue, demonstrating the ability to rationally design catalytic antibodies.
- Pedersen discovered crown ethers in 1967 which showed the first example of molecular recognition, an important concept in supramolecular chemistry.
- Cram established the concept of host-guest chemistry where a host molecule can bind to a guest molecule.
- Lehn introduced the term "supramolecular chemistry" in 1978 to describe intermolecular interactions beyond the covalent bond.
- Pedersen, Cram, and Lehn received the 1987 Nobel Prize in Chemistry for their contributions to supramolecular chemistry.
This document presents a study using quantum chemical calculations and molecular dynamics simulations to predict the corrosion inhibition performance of some thiazole and thiadiazole derivatives against iron corrosion. The study calculates quantum chemical parameters such as HOMO-LUMO energies, chemical hardness, and binding energies of the inhibitor molecules on an iron surface. The results agree with experimental data showing that compound Inh5 has the best inhibition efficiency for iron corrosion.
This document discusses a study using quantum chemical calculations and molecular dynamics simulations to predict the corrosion inhibition performance of some thiazole and thiadiazole derivatives against iron corrosion. The study calculates quantum chemical parameters such as HOMO-LUMO energies, chemical hardness, and binding energies of the inhibitor molecules on an iron surface. The results from these calculations are in good agreement with experimental inhibition efficiency data and can help identify the most effective inhibitor.
In the present study, to predict corrosion inhibition performances of 2-amino-4-(4-chlorophenyl)-thiazole
(Inh1), 2-amino-4-(4-bromophenyl)-thiazole (Inh2), 4-(2-aminothiazole-4-yl)-phenol (Inh3), 5,5′-(ethane-1,
2-diyldisulfanediyl) bis-(1,3,4-thiadiazole-2-amine) (Inh4), 5,5′-(propane-1,3-diyldisulfanediyl) bis-(1,3,4-
thiadiazole-2-amine) (Inh5) against corrosion of Fe metal, density functional theory (DFT) calculations and molecular
dynamics simulations approach were performed on these mentioned molecules. Firstly, quantum chemical
parameters such as the highest occupied molecular orbital energy (EHOMO), lowest unoccupied molecular
orbital energy (ELUMO), the energy gap between ELUMO and EHOMO (ΔE), chemical hardness, softness, electronegativity,
proton affinity, global electrophilicity, global nucleophilicity and total energy (sumof electronic and zeropoint
energies) were calculated and discussed with the help of HF/SDD, HF/6-311G, HF/6-31++G, B3LYP/SDD,
B3LYP/6-311G and B3LYP/6-31++Gmethods. Then, we calculated binding energies on Fe(110) surface of aforementioned
thiazole and thiadiazole derivatives to investigate the strength of the interactions between metal surface
and these molecules. The theoretical data obtained are in good agreement with the experimental inhibition
efficiency results earlier reported.
1. pubs.acs.org/joc
Anion Binding of Short, Flexible Aryl Triazole Oligomers
Hemraj Juwarker, Jeremy M. Lenhardt, Jos C. Castillo, Emily Zhao, Sibi Krishnamurthy,
e
Ryan M. Jamiolkowski, Ki-Hyon Kim, and Stephen L. Craig*
Department of Chemistry, Duke University, 124 Science Drive, Durham, North Carolina 27708
stephen.craig@duke.edu
Received September 19, 2009
The flexible, electropositive cavity of linear 1,4-diaryl-1,2,3-triazole oligomers provides a suitable
host for complexation of various anions. The binding affinities for various combinations of oligomer
and anion were determined by 1H NMR titrations. Effective ionic radius is found to be a primary
determinant of the relative binding interactions of various guests, with small but measurable
deviations in the case of nonspherical anions. Solvent effects are significant, and the strength of
the binding interaction is found to depend directly on the donor ability of the solvent. A picture
emerges in which anion binding can be effectively interpreted in terms of a competition between two
solvation spheres: one provided by the solvent and a second dominated by a folded cavity lined with
electropositive 1,2,3-triazole CH protons. Implications for rigid macrocycles and other multivalent
hosts are discussed.
Introduction in complementary interactions such as cation-π,1 π-π,2
nitrogen-halogen,3 donor-σ-acceptor,4 and hydrogen
The collective manipulation of individually weak inter-
bonds derived from C-H groups.5 While not traditionally
molecular interactions is central to a wide range of molecular
included in lists of potential hydrogen bond donors, suffi-
phenomena, including ligand-receptor interactions in bio-
ciently polar C-H bonds interact with both anionic and
logy, medicine, and sensors, polymer mechanical and trans-
neutral heteroatoms in a manner that places them on the
port properties, and the intra- and intermolecular contacts
weaker but still useful end of a continuum of hydrogen-bond
that guide the secondary structure of natural and synthetic
donors interacting with electron-rich partners.6
macromolecules. As a result of its strength and direction-
Recent reports demonstrate that the polarity of neutral 1,4-
ality, hydrogen bonding from conventional donors (H-X,
disubstituted aryl-1,2,3-triazoles (dipole moment∼5 D) and that
where X = N, O, or F) is a well-recognized and dominant
of the C5-H bond create an electropositive site that can function
interaction in many contexts, but it is increasingly clear that
as an effective hydrogen bond donor for anion binding.7-9
other chemical moieties hold promise as important partners
(5) (a) Chabinyc, M. L.; Brauman, J. I. J. Am. Chem. Soc. 2000, 122,
(1) Ma, J. C.; Dougherty, D. A. Chem. Rev. 1997, 97, 1303–1324. 8739–8745. (b) Castellano, R. K. Curr. Org. Chem. 2004, 8, 845–865.
(2) (a) Meyer, E. A.; Castellano, R. K.; Diederich, F. Angew. Chem., Int. (6) (a) Desiraju, G. R.; Steiner, T. The Weak Hydrogen Bond in Structural
Ed. 2003, 42, 1210–1250. (b) Paulini, R.; Muller, K.; Diederich, F. Angew. Chemistry and Biology; Oxford University Press: New York, 1999.
Chem., Int. Ed. 2005, 44, 1788–1805. (7) (a) Li, Y.; Flood, A. H. Angew. Chem., Int. Ed. 2008, 47, 2649–2652.
(3) Walsh, P. L.; Ma, S. H.; Obst, U.; Rebek, J. J. Am. Chem. Soc. 1999, (b) Li, Y.; Flood, A. H. J. Am. Chem. Soc. 2008, 130, 12111–12122.
121, 7973–7974. (8) Juwarker, H.; Lenhardt, J. M.; Pham, D. M.; Craig, S. L. Angew.
(4) (a) Li, H. F.; Homan, E. A.; Lampkins, A. J.; Ghiviriga, I.; Castellano, Chem., Int. Ed. 2008, 47, 3740–3743.
R. K. Org. Lett. 2005, 7, 443–446. (b) Lampkins, A. J.; Abdul-Rahim, O.; Li, (9) Meudtner, R. M.; Hecht, S. Angew. Chem., Int. Ed. 2008, 47, 4926–
H. F.; Castellano, R. K. Org. Lett. 2005, 7, 4471–4474. 4930.
8924 J. Org. Chem. 2009, 74, 8924–8934 Published on Web 11/03/2009 DOI: 10.1021/jo901966f
r 2009 American Chemical Society
2. Juwarker et al.
JOC Featured Article
Li and Flood synthesized a tetrameric aryl-1,2,3-triazole
macrocycle that demonstrated a high binding affinity (K=
105 M-1 in CD2Cl2) for chloride. A noteworthy feature of
the macrocyclic receptor is that it is devoid of conventional
H-X hydrogen-bond donors but rather interacts exclusively
via C-H chloride contacts.7 Juwarker et al. demonstrated
that when the same aryl triazole functionality is presented in
the form of a flexible oligomer, chloride binding induces a
pro-helical conformation in the oligomer, a folding pattern
that creates an electropositive cavity that is similar to but
lacks the preorganization of the macrocycle reported by Li
and Flood. The work by Juwarker et al. further demon-
strated that the strength of the interaction increases with the
generation of triazole-containing oligomer.8 Also around
the same time, Hecht et al. reported on the helicity inversion
of a pyridyl 1,2,3-triazole oligomer induced by binding to
achiral halides in highly polar solvents.9 FIGURE 1. Oligo(aryl-1,2,3-triazoles) 1 and 2 depicted in their
inferred anion binding conformations. Cavity binding triazole
The practical utility of 1,4-disubstituted-1,2,3-triazoles as
protons (Hc, Hh) and aryl protons (Ha, Hd) are labeled.
functional species in intra- and intermolecular interactions is
enhanced by the fact that they are readily accessible through
Given the utility of triazole CH-anion interactions in
the Cu(I)-catalyzed coupling of azides and alkynes.10 While
these and other contexts, we therefore set out to establish the
triazoles are historically viewed as “stealth” linkages with
structure-activity relationships that guide these interactions
negligible independent function, these recent reports of
in more detail. This manuscript extends our earlier report to
anion recognition11-14 build on a growing body of work
the interactions of short aryl-1,2,3-triazole oligomers with a
regarding the potential functionality of substituted triazoles.
range of anionic guests. The use of flexible hosts of various
For example, the size and dipole moment of 1,2,3-triazoles
lengths provides an opportunity to evaluate the intrinsic
make them interesting candidates for amide bond surro-
properties of triazole-anion interactions, thus providing a
gates in both a medicinal and structural context.15 Arora and
baseline from which to evaluate the effects of size and shape
co-workers have reported the contributions of triazoles to
complementarity found in increasingly ordered receptors.
the conformational preferences of mixed amide-triazole
The size of the anions, as described by their effective ionic
oligomers.16
radii, are found to be primary determinants of the strength of
binding by the flexible oligomers, with small but measurable
(10) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. deviations in the case of nonspherical anions. Further, the
Angew. Chem., Int. Ed. 2002, 41, 2596–2599. affinity of the receptors for a given anion is typically well
(11) For selected recent reports on hydrogen-bonding-based anion re-
ceptors, see: (a) Maeda, H. Eur. J. Org. Chem. 2007, 32, 5313–5325. (b)
correlated with the downfield shifts of the 1,2,3-triazole CH
Amendola, V.; Esteban-Gomez, D.; Fabbrizzi, L.; Licchelli, M. Acc. Chem. protons upon binding. This correlation provides a useful
Res. 2006, 39, 343–353. (c) Choi, K. H.; Hamilton, A. D. Coord. Chem. Rev. method for deconvolving the contributions to multivalent
2003, 240, 167–189. (d) Bondy, C. R.; Loeb, S. J. Coord. Chem. Rev. 2003,
240, 77–99. (e) Sessler, J. L.; Camiolo, S.; Gale, P. A. Coord. Chem. Rev. 2003, binding in the longer oligomers. An unexpected fluoride-
240, 17–55. (f) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed. 2001, 40, 486– catalyzed proton exchange reaction is observed in d6-ace-
516. (g) Suk, J. M.; Jeong, K. S. J. Am. Chem. Soc. 2008, 130, 11868–11869. tone. Finally, solvent effects on the binding of chloride are
(12) For selected recent reports on cationic anion receptors, see: (a)
Llinares, J. M.; Powell, D.; Bowman-James, K. Coord. Chem. Rev. 2003, 240, presented, and the CH-chloride interaction is found to
57–75. (b) Beer, P. D.; Hayes, E. J. Coord. Chem. Rev. 2003, 240, 167–189. (c) depend directly on the donor ability of the solvent. A picture
Beer, P. D. Acc. Chem. Res. 1998, 31, 71–80. (d) Ihm, H.; Yun, S.; Kim, H. G.;
Kim, J. K.; Kim, K. S. Org. Lett. 2002, 4, 2897–2900. (e) Mullen, K. M.;
emerges in which anion binding can be effectively interpreted
Mercurio, J.; Serpell, C. J.; Beer, P. D. Angew. Chem., Int. Ed. 2009, 48, 4781– in terms of a competition between two solvation spheres: one
4784. provided by the solvent and a second dominated by a folded
(13) For selected recent reports of CH-anion interactions, see: (a)
Bryantsev, V. S.; Hay, B. P. J. Am. Chem. Soc. 2005, 127, 8282–8283. (b) cavity lined with 1,2,3-triazole CH protons.
Bryantsev, V. S.; Hay, B. P. Org. Lett. 2005, 7, 5031–5034. (c) Fujimoto, C.;
Kusunose, Y.; Maeda, H. J. Org. Chem. 2006, 71, 2389–94. (d) Vega Iel, D.; Results and Discussion
Gale, P. A.; Light, M. E.; Loeb, S. J. Chem. Commun. 2005, 39, 4913–5. (e)
Belcher, W. J.; Fabre, M.; Farhan, T.; Steed, J. W. Org. Biomol. Chem. 2006,
4, 781–786. (f) Ilioudis, C. A.; Tocher, D. A.; Steed, J. W. J. Am. Chem. Soc.
When tetrabutylammonium salts of various anions are
2004, 126, 12395–12402. (g) Zhu, S. S.; Staats, H.; Brandhorst, K.; added to d6-acetone solutions of 1a and 2 (Figure 1), down-
Grunenberg, J.; Gruppi, F.; Dalcanale, E.; Luetzen, A.; Rissanen, K.; field shifts of the 1H NMR resonances of the 1,2,3-triazole
Schalley, C. A. Angew. Chem., Int. Ed. 2008, 47, 788–792.
(14) For a recent review of interactions between electron-deficient aro- CH protons and inner cavity aryl protons are observed,
matic rings and anions, see: Berryman, O. B.; Johnson, D. W. Chem. indicating a polarizing interaction in the oligomer cavity
Commun. 2009, 3143–3153. that we have previously attributed to anion binding.8 Speci-
(15) (a) Kolb, H. C.; Sharpless, K. B. Drug Discovery Today 2003, 8,
1128–1137. (b) Bourne, Y.; Kolb, H. C.; Radic, Z.; Sharpless, K. B.; Taylor, fically for oligomer 1a, addition of anion induces downfield
P.; Marchot, P. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 1449–1454. (c) Brik, shifts of triazole protons Hc and inner cavity aryl protons
A.; Alexandratos, J.; Lin, Y. C.; Elder, J. H.; Olson, A. J.; Wlodawer, A.;
Goodsell, D. S.; Wong, C. H. ChemBioChem. 2005, 6, 1167–1169. (d) Bock,
Ha. Similarly, for oligomer 2, titration with anion induces
V. D.; Speijer, D.; Hiemstra, H.; van Maarseveen, J. H. Org. Biomol. Chem. downfield shifts of triazole protons Hc, Hh and inner cavity
2007, 5, 971–975. (e) Pokorski, J. K.; Jenkins, L. M. M.; Feng, H. Q.; Durell, aryl proton Ha, suggesting in all cases a binding mode similar
S. R.; Bai, Y. W.; Appella, D. H. Org. Lett. 2007, 9, 2381–2383.
(16) (a) Angelo, N. G.; Arora, P. S. J. Am. Chem. Soc. 2005, 127, 17134– to that established previously for chloride and fluoride
17135. (b) Angelo, N. G.; Arora, P. S. J. Org. Chem. 2007, 72, 7963–7967. (Figure 2).
J. Org. Chem. Vol. 74, No. 23, 2009 8925
3. JOC Featured Article Juwarker et al.
FIGURE 2. Partial 1H NMR spectra (400 MHz, d6-acetone, 298 K) of oligo(aryl-1,2,3-triazoles) with and without Bu4NþCl-: (i) 1 mM 1a, (ii)
1 mM 1a þ 1 mM Bu4NþCl-, (iii) 1 mM 2, and (iv) 1 mM 2 þ 1 mM Bu4NþCl-. Downfield shifts of binding protons are denoted by dashed
lines. Similar effects of varying magnitude are observed for all of the ions reported.
TABLE 1. Anion Binding Constants of Oligo(aryl-1,2,3-triazoles) 1 3 X- and 2 3 X- Obtained from 1H NMR Titration (1 mM, d6-acetone, 298 K) with
(Bu)4NþX-a
anion (X-) K (1a 3 X-) (M-1) δmax (ppm) K (2 3 X-) (M-1) δ max(i) (ppm) δ max(o) (ppm)
Cl- 1260 (30) 2.03 (0.02) 1.2 (0.4) Â 104 1.63 (0.03) 1.08 (0.03)
Br- 470 (30) 1.45 (0.05) 1.1 (0.2) Â 104 1.52 (0.01) 1.11 (0.01)
I- 43 (1) 1.23 (0.02) 1.4 (0.2) Â 103 1.21 (0.01) 0.91 (0.01)
PhCO2- 1150 (70) 1.77 (0.02) 4.3 (0.2) Â 103 1.34 (0.06) 0.76 (0.04)
HSO4- 160 (30) 0.61 (0.03) 2.7 (0.6) Â 103 0.67 (0.01) 0.67 (0.02)
NO3- 35 (3) 0.64 (0.02) 910 (50) 0.63 (0.01) 0.60 (0.01)
PF6- 1.7 (0.6) 0.08 (0.02) 4 (2) 0.30 (0.07) 0.32 (0.07)
a
δmax (ppm) = calculated maximum change ( ) in chemical shift (δ) of 1,2,3-triazole proton Hc upon anion binding. Subscripts denote inner (i) and
outer (o) 1,2,3-triazole protons for oligomer 2 (Hc and Hh). The titration data were fit by Benesi-Hildebrand, Scatchard, and nonlinear regression
methods.18 All three methods gave similar results, and the individual fits are provided in the Supporting Information. For convenience and clarity, the
average binding constants and variation due to choice of method (in parentheses) are presented here. None of the conclusions of this work rely on the
choice of fitting method. Absolute uncertainties arise from uncertainties in the concentrations and the possibility of subtle aggregation and/or dielectric
effects on chemical shift as a function of salt concentration. These absolute uncertainties are estimated to be less than 50% in K and less than 5% in
δmax. Binding constants reported for oligomer 2 are the average of binding constants derived from fits of both the inner and outer triazole protons.
In all cases, a 1:1 binding stoichiometry is determined by from geometric complementarity between host and guest. In
Job’s Method of Continuous Variation.17 The anion-binding the case of benzoate in particular, the distribution of negative
strength of oligo(aryl-1,2,3-triazoles) 1a and 2 were deter- charge is not isotropic but is concentrated in the plane of the
mined in d6-acetone from titrations with seven different carboxylate group and away from the formally uncharged
anions of varying size, geometries, and basicities (Table 1). phenyl group (Figure 5). Etter has pointed out that this
Trends in the binding affinities of each oligomer are dis- electrostatic distribution favors anti hydrogen bonding pat-
cussed sequentially, below, followed by comparisons be- terns that are well met in this case by host 1a (Figure 5),19 a
tween the two. feature that has been exploited in oxoanion receptors pre-
Oligo(aryl-1,2,3-triazole) 1a 3 X-. Oligomer 1a displays a viously20 and which reinforces the hypothesis of a geometric
1:1 binding stoichiometry with all of the studied anions origin to the deviation in Figure 4. The concentrated charge
(Figure 3). The relative anion binding strengths of 1a in d6- in benzoate relative to the spherical halides is also related to
acetone (Table 1) are its high β value (2.01), where β reflects the hydrogen-bonding
proton acceptor ability relative to hydrogen ion as obtained
Cl - ∼ C6 H5 CO2 - Br - HSO4 - I - ≈ NO3 - PF6 - from Kamlet-Taft parameters.21 We do find a rather weak
correlation between binding affinity and β (data not shown),
It is evident that as the size of the anion increases, the although we note that β and ionic radius will share an
binding strength decreases, a correlation that is consistent intrinsic correlation that complicates an efficient separation
with the expected electrostatic nature of the ion binding of the two effects. Couching the apparent intrinsic selectivity
interaction (Figure 4). Small deviations are observed, how- of 1a for benzoate in terms of geometric complementarity
ever, in the case of benzoate (a tighter binder than expected seems, therefore, to be more appropriate.
from its size) and nitrate (a weaker binder than expected Li and Flood have reported halide binding studies of a
from its size). The magnitude of these deviations is rather related acyclic oligo(aryl-1,2,3-triazole) that displays size
small (∼1 kcal mol-1), but they indicate a subtle contribution
(19) G€rbitz, C. H.; Etter, M. C. J. Am. Chem. Soc. 1992, 114, 627–631.
o
(20) (a) Smith, P. J.; Reddington, M. V.; Wilcox, C. S. Tetrahedron Lett.
(17) Job, P. Ann. Chim. 1928, 9, 113–203. 1992, 41, 6085–6088. (b) Fan, E.; van Arman, S. A.; Kincaid, S.; Hamilton,
(18) Connors, K. A., Binding Constants; John Wiley Sons: New York, A. D. J. Am. Chem. Soc. 1993, 115, 369–370.
1987; pp 128-136. (21) Marcus, Y. Ion Properties; Marcel Dekker: New York, 1997.
8926 J. Org. Chem. Vol. 74, No. 23, 2009
4. Juwarker et al.
JOC Featured Article
FIGURE 5. Electrostatic potential maps (Spartan) of benzoate
(left) and an aryl triazole trimer (right) showing the complementa-
rity of the anisotropic electrostatic distributions, each of which is
concentrated in the plane. Red denotes regions of negative charge,
and blue denotes regions of positive charge.
selectivity for the larger Br- and I- over Cl- and F- in
CD2Cl2, a trend that differs from that found here for 1a in d6-
acetone as a solvent.7b The selectivity observed in Li and
Flood’s linear oligomers further differs from that reported
by the same authors for an aryl-1,2,3-triazole macrocycle in
FIGURE 3. Job’s plots of 1a 3 X- displaying 1:1 binding stoichio- which the fixed cavity favors Cl- and Br-. Together, these
metries with the Bu4Nþ salts of Cl-, Br-, I-, and HSO4- (d6- differences indicate that anion selectivity is not an intrinsic
acetone, 298 K). PhCO2-, NO3-, and PF6- also display similar property of aryl-1,2,3-triazole functional groups but rather a
binding stoichiometries and are omitted for clarity but included in confluence of geometric and solvation effects, which we
the Supporting Information. Gaussian fit of data points was explore further below.
performed using Origin 7.0. Inner triazole proton Hc displays a Differences in anion binding strengths reflect differences
1:1 binding stoichiometry with all measured X-. δ (ppm) =
change in 1H chemical shift of monitored protons Hc. X1 = mole between electrostatic interactions (ion-dipole, ion-induced
fraction of oligomer 1a. Xanion = mole fraction of anion during data dipole) and geometric distortions of the host-guest sys-
collection. tem.22 Electrostatic effects are reflected by the magnitude
of the induced downfield shifts in the CH proton resonances
of the fully bound hosts ( δmax), and we find for 1a a
reasonable correlation between δmax and the anion binding
constant K (Figure 6). Chloride, for example, is the best guest
and induces the largest difference in CH chemical shift
between the fully complexed and uncomplexed species
( δmax =2.03 ppm) compared to the weak binding of PF6-
( δmax =0.08 ppm), with the other anions in between. The
larger, spherical halides Br- and I- bind more weakly than
Cl- and have lower induced chemical shifts ( δmax of 1.45
and 1.23 ppm, respectively). This correlation between mag-
nitude of chemical shift and binding strength is similar to
that which forms the basis of the Guttman acceptor num-
ber,23 and similar correlations have been reported pre-
viously, for example, in a recent study by Jeong and co-
workers.24 For the triazole oligomers, a respectable linear
free energy relationship is observed (Figure 6). It is of interest
to note that benzoate fits the chemical shift trend quite well
( δmax = 1.8 ppm, K = 103 M-1), in comparison to its
deviation with respect to ionic radius (Figure 4). The good
fit of benzoate with respect to induced chemical shift
(Figure 6) further supports that its higher affinity relative
(22) Bandyopadhyay, I.; Raghavachari, K.; Flood, A. H. Chem-
PhysChem 2009, 10, 2535–2540.
(23) (a) Mayer, U.; Gutmann, V.; Gerger, W. Monatsh. Chem. 1975, 106,
FIGURE 4. Correlation of anion binding strength to ionic radius 1235–1257. (b) Mayer, U. Coord. Chem. Rev. 1976, 21, 159–179. (c) Gutmann,
V. The Donor-Acceptor Approach to Molecular Interactions; Plenum Press:
for oligomer 1a. Ionic radii obtained from Goldschmidt and Pauling New York, 1978.
crystal data correlations as compiled by Marcus.21 Error bars reflect (24) Chang, K.-J.; Moon, D.; Lah, M. S.; Jeong, K.-S. Angew. Chem., Int.
the uncertainty associated with choice of binding isotherm. Ed. 2005, 44, 7926–7929.
J. Org. Chem. Vol. 74, No. 23, 2009 8927
5. JOC Featured Article Juwarker et al.
FIGURE 6. Correlation of calculated chemical shift change ( δmax) with anion binding strength (K) of oligomer 1a. Data obtained by 1H
NMR titration of 1a (1 mM; d6-acetone, 298 K) and calculation of δmax performed by nonlinear regression curve fitting of 1H NMR data by
Origin 7.0. δmax is the calculated induced chemical shift of triazole proton Hc (ppm) when bound to anion. Error bars denote the uncertainty
associated with the choice of isotherm fitting method.
FIGURE 7. Job’s plots of 2 3 X- (d6-acetone, 298 K) displaying 1:1 binding stoichiometries with the Bu4Nþ salts of Cl-, Br-, I- and HSO4-.
Benzoate, NO3- and PF6- also display 1:1 binding but are omitted for clarity and included in the Supporting Information. X2 = mole fraction
of oligomer 2. Xanion = Mole fraction of anion. δ is the induced change in 1H NMR chemical shift of triazole protons Hc upon anion binding
(ppm).
to ionic radius is due to stronger electrostatic interactions aggregates at higher concentrations. Such aggregation is
between the negative charge of the guest and partial positive evident by 1H NMR through extreme broadening and
charge distribution in the host, rather than an effect due to, eventual coalescence of the aromatic protons. At the lower
for example, interactions between the host and the aromatic concentrations, Job’s plots confirmed a 1:1 binding stoichio-
ring of the guest. The only apparent exception to the metry for all anions with oligomer 2 (Figure 7).
correlation between binding strength and induced chemical 1
H NMR titration with the corresponding Bu4Nþ salts
shift is hydrogen sulfate (K=140 M-1, δmax =0.62 ppm), and subsequent nonlinear regression curve fitting enabled
which has a lower δmax and higher K than iodide (K=48 the quantitative determination of binding affinities, which
M-1, δmax = 1.16 ppm). We note that weak binding are reported in Table 1. The relative anion binding affinities
interactions are potentially more susceptible to systematic of 2 were determined to be
uncertainty, for example, due to minor contributions from Cl- Br- C6 H5 CO2 - HSO4 - I- ≈ NO3 - PF6 -
aggregation, and that erroneously low δmax will lead to
erroneously high K, exaggerating apparent differences. Even The trend in anion binding observed for 2 is similar to that
if both the precision and accuracy of the measured values observed for 1a, in that larger anions lead to weaker binding.
were certain, however, the magnitude of the deviations are As seen for 1a, a reasonable correlation between induced
sufficiently small (1.5 kcal mol-1 per ion from the values chemical shift ( δmax) and binding affinity K is found
expected from the remainder of the series) that they defy a (Figure 8). The magnitude of the induced chemical shift
meaningful explanation. provides an interesting insight into the nature of these multi-
Oligo(aryl-1,2,3-triazole) 2. We next consider the extent to valent interactions. When the total chemical shifts (e.g., in
which these same trends in binding extend to the longer Hc þ Hh for 2 versus Hc only in 1a) are considered, the binding
oligomer 2. The concentration of oligomer 2 was kept at 1 data versus induced chemical shift for 1a and 2 collapse
mM in order to overcome the formation of π-stacked reasonably well onto a single master curve (Figure 8, right).
8928 J. Org. Chem. Vol. 74, No. 23, 2009
6. Juwarker et al.
JOC Featured Article
FIGURE 8. (Left) Correlation of the sum of the calculated chemical shift changes ( δmax) of the outer and innter triazole protons upon anion
binding with anion binding strength (K) of oligomer 2. Data obtained by 1H NMR titrations of 2 with Bu4NþX- (1 mM; d6-acetone, 298 K) and
calculation of δmax obtained by nonlinear regression curve fitting of 1H NMR data by Origin 7.0. (Right) Correlation of total chemical shift
change of triazole protons upon anion binding with anion binding strength for oliomers 1a and 2. Error bars denote the uncertainty associated
with the choice of isotherm fitting method.
The individual interactions, insofar as they are accurately binding mode is not optimal for hydrogen-bonding-type
reported by the induced chemical shifts, therefore are additive interactions.19 Even if benzoate were able to maintain a
and can be compared from one oligomer to another. For coplanar binding geometry with host 2, however, the non-
example, the δmax differences associated with chloride bind- symmetrical distribution of negative charge in the carbo-
ing in 1a and 2 (2.03 ppm for 1a versus 1.63 ppm for the inner xylate would prevent simultaneous CH-anion interactions
triazole proton and 1.08 for the outer triazole proton of 2) can between the effectively circularly symmetric host and un-
be used to infer further structural details of multivalent symmetric guest. This effect of uneven charge distribution is
binding.25 The fact that oligomer 2 has a larger binding similar to that observed in trends in the progressive aqueous
affinity for chloride (K 104 M-1 for 2 versus K = 1280 solvation of carboxylates. The addition of a first molecule of
M-1 for 1a) is not due to tighter interactions of chloride with water to acetate in vacuo, for example, is more exothermic
individual triazole CH protons; on the contrary, the indivi- than the addition of a single molecule of water to chloride,
dual interactions appear to be weaker (the individual δmax although the overall bulk aqueous solvation energy of
values for both the inner and outer triazole CH resonances are acetate is considerably lower than that of chloride.27 One
smaller for 2 than for 1a). Instead, the weakening of individual (and potentially a second) directional, hydrogen-bonding-
contacts is overcome by the increased number of triazole CH type interaction interacts strongly with the concentrated,
donors. directional charge distribution of the carboxylate, but sub-
The major difference in binding trends between the two sequent solvating interactions have significantly less effect
oligomers is the relative binding strengths of bromide and relative to spherical anions of comparable size. Here, the
benzoate. In the smaller oligomer 1a, benzoate binds more crescent-shaped host 1a effectively saturates the preferred,
tightly than bromide (1150 versus 470 M-1), whereas in the “specific” binding region on benzoate, and increasing the
longer oligomer 2, bromide binds more tightly than benzoate generation of the host generates rapidly diminishing returns
(1.1 Â 104 versus 4.3 Â 103 M-1). Notably, that difference is in binding constant, a picture that is supported by the
consistent with the differences in δmax, which is smaller for significant difference in induced δmax values for the inner
2 3 benzoate than 1a 3 benzoate, implying a poorer fit of (1.31 ppm) and outer (0.74 ppm) triazole CH protons upon
benzoate within the pseudocircular cavity of 2. Oligomer 2 binding to benzoate. Therefore, in terms of geometric com-
is longer than its counterpart, and in order to simultaneously plementarity, the isotropic charge distribution on bromide is
maximize CH-anion contacts and preserve planarity, it a better fit for 2 than is the anisotropic charge distribution on
must wrap around anions to form a cavity that is at least benzoate, while the reverse is true for 1a. Overall, the effect of
partially “closed off” by the terminal aryl groups. It can size/shape complementarity on binding in the linear oligo-
therefore be envisioned that in a fully “wrapped” oligomer 2, mers is much less than that in the rigid macrocycles reported
benzoate must bind perpendicularly to the plane of the by Li and Flood, but these results suggest that the onset of
triazoles, as the overall size of benzoate would disallow some geometric effects occurs in linear oligomers of compar-
planar entry into the binding cavity that is allowed by 1a. able size, without the need for covalent conformational
The perpendicular binding of benzoate in the cavity of restraints.
calixpyrroles has been reported previously by Sessler,26 and Fluoride Binding. Fluoride is a common and important
it is well-known from Etter’s seminal work that such a target for anion binding, and its absence from the previous
discussion is likely conspicuous. Studying fluoride binding in
(25) Badjic, J. D.; Nelson, A.; Cantrill, S. J.; Turnbull, W. B.; Stoddart, J. heterocyclic anion receptors is often problematic because of
F. Acc. Chem. Res. 2005, 38, 723–732.
(26) (a) Piatek, P. L.; Lynch, V. M.; Sessler, J. L. J. Am. Chem. Soc. 2004,
126, 16073–16076. (b) Sessler, J. L.; Barkey, N. M.; Pantos, G. D.; Lynch, V. (27) Kelly, C. P; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B. 2006,
M. New J. Chem. 2007, 31, 646–654. 110, 16066–16081.
J. Org. Chem. Vol. 74, No. 23, 2009 8929
7. JOC Featured Article Juwarker et al.
FIGURE 9. Aggregation effects indicated by 1H NMR spectra upon addition of Bu4NþF- to a 1 mM solution of oligomer 2 in d6-acetone.
Addition of 1 equiv of F- results in severe peak broadening.
the inherent basicity of the fluoride anion (β = 2.88, com-
pared to 1.67 for Cl-), and such is the case here. The fluoride
anion can form very stable hydrogen bonds, for example, in
polynuclear aggregates such as HF2-. Hydrofluoric acid is a
relatively weak acid (pKa = 3.2), and in urea-based and
pyrrole-based anion receptors, fluoride has been shown to
deprotonate the acidic NH hydrogen bond donor to form
two separate species, L- and HF2-, according to the reac-
tion28
HL þ 2F- f L- þ HF2 -
where HL is the protic fluoride receptor, a role filled here by
the triazoles (vide infra). FIGURE 10. Effect of high fluoride concentration (55 mM, 11
equiv) on disappearance of the 1H NMR resonance of the triazole
In the case of oligomer 2, the use of Bu4NþF- complicates
proton of 3 (5 mM) in d6-acetone. The effect is quite extreme, as seen
quantitative study by inducing aggregation to a much greater from the drastic reduction in intensity over time of the sharp 1,2,3-
extent than the other salts (Figure 9). Nonetheless, at low triazole CH singlet that is originally at δ = 9.15 ppm.
concentrations of F- in d6-acetone, a reasonable 1H-1H
NOESY spectrum has previously been reported that indi- of F- in d6-acetone reveals an increase of 1 Da in the parent
cates a 2 3 F- binding mode similar to that of 2 3 Cl-.8 ion peak (from 456.21 to 457.21), consistent with a single
Aggregation is less problematic for the shorter oligomer 1a H/D exchange. The combination of proton transfer and the
and diaryltriazole 3, but the addition of more than 1 equiv of apparent requirement of 1 equiv of F- for host deproto-
F- leads to deprotonation of the triazole CH protons nation supports an HF2- mediated pathway (with possible
(Figures 10 and 11). For example, while there is no sub- contributions from H2OF- through adventitious water)
stantial change in the intensity of the triazole CH proton similar to that observed previously in ureas and calixpyr-
resonance upon addition of 0.8 equiv of Bu4NþF- to 1a, the roles.28 We note that similar processes may contribute to the
addition of 3 equiv results in a pronounced loss of intensity aggregation of 2, which is more pronounced when 1 equiv
over a few hours (Figure 11). A similar effect is noticed upon of Bu4NþF- is used (Figure 9). These behaviors present
the addition of 1.2 equiv; however, the loss of the CH obvious challenges to quantifying F- binding, resulting in its
resonances takes considerably longer. For both 3 and 1a omission from our binding studies.
(Figure 12), the triazole CH proton resonance is not restored Solvent Effects. Molecular recognition in any solvated
when AgNO3 is added to precipitate F- as the silver salt, environment depends on the nature of the interactions
indicating a chemical change in the triazoles. between host and guest, but it also involves at least partial
We attribute the loss of the CH resonance to fluoride- desolvation of both the free host and the free guest in order to
catalyzed proton/deuteron exchange between the aryl-1,2,3- facilitate the host:guest interactions.29 When ionic species
triazoles and d6-acetone, a hypothesis supported by repeti- are present, these desolvation penalties can be enormous: in
tion of the F-/AgNO3 sequence in protio acetone, after the case of anionic guests, the desolvation penalty is espe-
which 3 is isolated and returned to deuterated solvent, and cially severe in protic solvents. We anticipated that anion
the triazole CH resonance is found intact (Figure 12). In (de)solvation would be a major factor in the present systems,
addition, mass spectrometry of 3 after exposure to 1 equiv and we therefore investigated the solvent dependency of
chloride recognition by 1H NMR titration experiments of
1a with (Bu)4NþCl- in d6-acetone, CD2Cl2, CD3CN,
(28) (a) Boiocchi, M.; Del Boca, L.; Gomez, D. E.; Fabbrizzi, L.;
Licchelli, M.; Monzani, E. J. Am. Chem. Soc. 2004, 126, 16507–16514. (b)
Gu, R.; Depraetere, S.; Kotek, J.; Budka, J.; Wagner-Wysiecka, E. W.; (29) (a) Lamb, M. L.; Jorgenson, W. L. Curr. Opin. Chem. Biol. 1997, 1,
Biernat, J. F.; Dehaen, A. Org. Biomol. Chem. 2005, 3, 2921–2923. (c) Evans, 449–457. (b) Sessler, J. L.; Gross, D. E.; Cho, W.-S.; Lynch, V. M.;
L. S.; Gale, P. A.; Light, M. E.; Quesada, R. New J. Chem. 2006, 30, 1019– Schmidtchen, F. P.; Bates, G. W.; Light, M. E.; Gale, P. A. J. Am. Chem.
1025. Soc. 2006, 128, 12281–12288.
8930 J. Org. Chem. Vol. 74, No. 23, 2009
8. Juwarker et al.
JOC Featured Article
FIGURE 11. (Left) 1 mM 1a þ 0.8 equiv of Bu4NþF- shows no pronounced decrease in the intensity of the triazole CH proton. (Right) 1 mM
1a þ 3 equiv of Bu4NþF- shows a gradual disappearance of the triazole CH proton resonance.
FIGURE 12. 1H NMR spectra of 3 3 F- showing that triazole proton disappearance is reliant upon acetone being in the deuterated form. (a) In
protic acetone solvent, the triazole CH 1H NMR resonance (He) persists after 24 h with excess fluoride. (b) Upon switching to deuterated
solvent, the triazole CH 1H NMR resonance (He) completely disappears. (c) Excess fluoride in conjunction with deuterated acetone is necessary
to cause the triazole CH 1H NMR resonance to disappear, as 3 in d6-acetone without fluoride yields no change in the 1H NMR resonance of
triazole CH proton He. The slight downfield shift of the CH resonance in (a) relative to (c) is attributed to partial association with residual
nitrate. Mass spectral data (see Supporting Information) support the assignment of deuterated oligomer 3 (right) after fluoride treatment in d6-
acetone.
DMSO, CDCl3, and 1:1 d6-acetone:cosolvent mixtures. As Table 2 shows that as AN decreases, the anion binding
expected, the choice of solvent exerts a large effect on the affinity K increases.32 The trend includes 1:1 solvent mixtures
affinity of the aryl-1,2,3-triazole receptor for the anionic of acetone with high AN solvents, for which the binding
guest (Table 2); the magnitude of the stability constants strength is larger than that of the pure solvents themselves.
varies by over 2 orders of magnitude across the series, and The exceptions to the trend are DMSO and the 1:1 acetone/
1a shows the highest chloride binding constant in d6-acetone. DMSO cosolvent. We note that DMSO is an excellent
There is no quantitative correlation between binding con- acceptor of localized positive charge (e.g., that of a hydrogen
stant and either dielectric constant and dipole moment, but a bond proton donor) and hypothesize that it competes with
good correlation was found with the Gutmann acceptor chloride for the triazole CH donors. Support for this hypoth-
number (AN) of the solvents, which gives a quantitative esis is found in the downfield shift of the triazole CH protons
measure of the solvent’s ability to accept and/or donate in DMSO (9.642 ppm) relative to the other solvents
electron density, for example, through hydrogen-bonding- (8.42-9.35 ppm), consistent with the acidic nature of the
type electrostatic interactions.23,30 C4-H proton.33 Anion complexation, therefore, is dominated
by a competition between the electrostatic interactions bet-
ween solvent and anion versus those between the host and
(30) For an overview on empirical solvent parameters, see: (a) Reichardt,
C. Solvents and Solvent Effects in Organic Chemistry; Wiley-VCH: Weinheim,
anion. These trends readily explain the apparent discrepancy
2003. For binary solvent parameters: (b) Marcus, Y. Solvent Mixtures-Proper- in anion selectivity observed here for host 2 and reported
ties and Selective Solvation; Marcel Dekker: New York, 2002. (c) Mancini, P. M. previously by Li and Flood for a related, acyclic tri-
E.; Terenzani, A.; Gasparri, M. G.; Vottero, L. R. J. Phys. Org. Chem. 1995, 8,
617–625. (d) Schmid, R.; Sapunov, V. N. Non-Formal Kinetics. In Search for azolophane.7b In our experiments, conducted in d6-acetone,
Chemical Reaction Pathways; Verlag Chemie: Weinheim, 1982. (e) Schmid, R.
Solvent Effects on Chemical Reactivity. In Handbook of Solvents; Wypych, G.,
Ed.; ChemTec Publishing: Toronto, 2001; Chapter 13 . (32) A similar correlation between binding strength of anions and AN is
(31) (a) Kamlet, M. J.; Taft, R. W. J. Am. Chem. Soc. 1976, 98, 377–383. described in Beer, P. D.; Shade, M. Chem. Commun. 1997, 24, 2377–2378.
(b) Kamlet, M. J.; Doherty, R. M.; Abboud, J. L.; Abraham, M. H.; Taft, R. (33) Matulis, V. E.; Halauko, Y. S.; Ivashkevich, O. A.; Gaponik, P. N.
W. J. Pharm. Sci. 1986, 75, 338–349. THEOCHEM 2009, 909, 19–24.
J. Org. Chem. Vol. 74, No. 23, 2009 8931
9. JOC Featured Article Juwarker et al.
TABLE 2. Effect of Solvent on the Chloride Binding Affinity of 1 distribution. There is no evidence from the trends that the
acceptor pseudocircular cavity presents a “special” binding arrange-
solvent K (M-1)a δmax (ppm) number (AN)b ment for appropriately sized ions.
acetone 1260 (30) 2.03 (0.02) 12.5 These results prompt an interesting question: if a tightly
1:1 acetone/DMSO 27 (1) 1.48 (0.03) 17.3 enforced circular cavity is not particularly advantageous for
1:1 acetone/CD2Cl2 110 (3) 1.95 (0.01) 18.7 anion binding, why are the anion binding affinities of the
1:1 acetone/CD3CN 100 (3) 2.03 (0.01) 19.2
DMSO 5.1 (0.4) 1.34 (0.08) 19.3
macrocyclic receptors reported by Li and Flood up to 5
1:1 acetone/CDCl3 61 (6) 1.40 (0.08) 20.3 orders of magnitude stronger than those of the related acyclic
CD2Cl2 34 (1) 2.37 (0.04) 20.4 oligomers?7b The entropic benefits of preorganization must
CDCl3 18 (1) 2.6 (0.1) 23.1 surely play a role, but the number of conformational degrees
a
Binding constants obtained from 1H NMR titration of oligomer 1 (1 of freedom that are lost upon anion binding is rather modest.
mM, 298 K) with Bu4NþCl-. The titration data were fit by Benesi- Because the orientation of the terminal aryl groups in 2 is
Hildebrand, Scatchard, and nonlinear regression methods.18 All three
methods gave similar results, and the individual fits are provided in the
likely to be a minor contributor to binding, there are only six
Supporting Information. For convenience and clarity, the average aryl-triazole single bond torsions that are expected to be
binding constants and variation due to choice of method (in parentheses) restricted upon anion complexation. Each of these torsions
are presented here. None of the conclusions of this work rely on the would be expected to be dominated by two fairly narrow
choice of fitting method. Absolute uncertainties arise from uncertainties regions of values centered at 0° and 180° in the unbound
in the concentrations and the possibility of subtle aggregation and/or
dielectric effects on chemical shift as a function of salt concentration. oligomer, and each would be limited to only one of those
These absolute uncertainties are estimated to be less than 30% in K and ranges upon idealized anion binding. The entropic penalty
less than 5% in δmax. bAcceptor numbers for pure solvents obtained associated with that reduced conformational freedom is
from Gutmann et al.23 For 1:1 solvent mixtures, AN is calculated from seemingly inadequate to explain a difference in binding
Dimroth-Reichardt parameters ET.30 ET values for 1:1 solvent mixtures
were derived from linear solvation energy relationships of solvatochro-
affinity of several orders of magnitude between the macro-
mic parameters described in detail by Kamlet and Taft.31 cyclic and acyclic triazole oligomers.34 For comparison, the
complete loss of torsional entropy upon binding has been
chloride is found to be a better guest than bromide, whereas calculated for similar rotors to be ∼11 eu.34a Even if all six
Li and Flood observed that a similar acyclic receptor bound rotors were completely frozen upon anion binding (which
bromide more tightly than chloride in CD2Cl2. The change in surely overestimates the actual entropic loss), then the total
anion selectivity can be attributed to differential solvation; cost in free energy of just over 4 kcal mol-1 is not sufficient to
the smaller chloride ion is better solvated than bromide. account for the reported differences between the rigid macro-
When the binding studies are conducted in CD2Cl2 versus d6- cycles and acyclic oligomers.
acetone, therefore, the increased donor ability of the CD2Cl2 A complementary effect could be that the macrocyclic
will stabilize the free chloride more than its bromide counter- receptor preorganizes the triazoles not so that they are well-
part. The magnitude of the selectivity for chloride over positioned to maximize the interactions between the receptor
fluoride in the macrocyclic receptors of Li and Flood is and the anionic guests; after all, the charge distribution in
similarly expected to have a significant solvent dependency, most of the ions is not heavier within an equatorial plane.
as solvation energies of fluoride are much larger than those Rather, the macrocycles might achieve higher affinity by
of chloride.27,30a preorganizing the electropositive C-H end of the triazole
Implications for Receptor Design. When considering anion dipoles so that they create repulsive interactions in the un-
binding in the acyclic receptors 1a and 2, perhaps the most bound host (that is, whereas the unbound state of the acyclic
significant conclusion is the lack of major surprises. The receptor can relax to a lower-energy conformation, the
identified trends in binding are largely valid across the entire shape-persistent macrocycle can not) and/or a cavity that
series of anion guests with only a few deviations, which are can only be filled at additional entropic and enthalpic
typically of a fairly small magnitude. Anion binding varies penalty by the surrounding solvent.35 In other words, macro-
relatively smoothly with ion size, the number and strength of cyclization might destabilize the unbound state of the host
individual triazole-anion contacts in the host, and the donor rather than stabilizing the bound host:guest complex. This
ability of the solvent. Even in cases where deviations are type of contribution, while often less discussed than con-
observed, they are relatively minor (generally ∼1 kcal mol-1 tributions due to favorable preorganization, is a well-known
or less). These results suggest a model of anion binding in contributor to the macrocyclic effect and similar multivalent
which the host-guest interaction can be thought of in terms binding processes.36 Support for the importance of destabi-
of a transfer of anion from the solvation sphere provided by lization in the unbound host in these systems comes from
the solvent to a partial solvation sphere provided by the aryl several sources. For example, we note that in the crystal
triazole host. Any contributions from shape- or size-com- structure of the triazole oligomer 1b (Figure 13), the triazoles
plementary “molecular recognition” are relatively minor. As
shown in our prior work, for example, the host 2 can wrap (34) (a) Mammen, M.; Shakhnovich, E. I.; Whitesides, G. M. J. Org.
neatly around the chloride ion to form a pseudocircular Chem. 1998, 63, 3168–3175. (b) Schmidtchen, F. P. Coord. Chem. Rev. 2006,
250, 2918–2928. (c) Hunter, C. A. Angew. Chem., Int. Ed. 2004, 43, 5310–
cavity for binding that is reminiscent of the macrocycles of 5324. (d) Schneider, H.-J. Angew. Chem., Int. Ed. 2009, 48, 3924–3977.
Li and Flood. The ability to do so, however, presents no (35) (a) Zhang, B.; Breslow, R. J. Am. Chem. Soc. 1993, 115, 9353–9354.
great advantage: iodide is incapable of fitting into the planar (b) Calderone, C. T.; Williams, D. H. J. Am. Chem. Soc. 2001, 123, 6262–
6267.
binding site, but it (presumably) accesses another host (36) (a) Mammen, M.; Choi, S.-K.; Whitesides, G. M. Angew. Chem., Int.
conformation that provides high-quality CH contacts Ed. 1998, 37, 2754–2794. (b) Christensen, T.; Gooden, D. M.; Kung, J. E.;
Toone, E. J. J. Am. Chem. Soc. 2003, 125, 7357–7366. (c) Tobey, S. L.;
and results in a binding affinity only 1 order of magnitude Anslyn, E. V. J. Am. Chem. Soc. 2003, 125, 10963–10970. (d) Kitov, P. I.;
lower than that of chloride, despite its more diffuse charge Bundle, D. R. J. Am. Chem. Soc. 2003, 125, 16271–16284.
8932 J. Org. Chem. Vol. 74, No. 23, 2009
10. Juwarker et al.
JOC Featured Article
FIGURE 13. Partial crystal structure of oligomer 1b (oligoethyleneglycol units truncated for clarity; see Supporting Information for complete
structure), showing the alternating orientation of the triazole dipoles.
adopt a zigzag “anti” conformation that minimizes the internal interaction is well-correlated with the effective ionic radius of
dipole of the molecule in a way that is obviously inaccessible to the anion (smaller anions are bound more tightly), the total
the macrocycle. Arora and co-workers16 have previously noted induced chemical shifts of all interacting triazole CH protons
similar conformational preferences in oligomeric triazoles, and (greater shifts are associated with stronger interactions), and
calculations on the macrocyclic receptors reveals puckering of the Gutmann number of the solvent (better hydrogen bond
the unbound (but not anion-complexed) planar macrocycle, donors lead to weaker binding). Increasing the number of
presumably to relieve hydrogen-hydrogen repulsions.22 The triazoles in the linear oligomers leads to a decrease in the
conformation of the oligomer without anion is in marked magnitude of the individual CH-anion contacts, but over-
contrast to the crystal structure of a related oligomer:chloride comes that penalty through the multivalent presentation of
complex reported previously,8 in which the triazoles neatly additional hydrogen-bond-type donors. Geometric comple-
wrap around the anion partner in the expected geometry. mentarity appears to have a modest but measurable effect on
This qualitative structural evidence is supported by pre- the binding of benzoate, but in general these results suggest a
viously reported calculations from Li and Flood,7b in which model in which the host-guest interaction is dominated by
the “anti” arrangement of unrestricted triazoles is favored by what can be thought of as a partial transfer of anion from one
∼2 kcal mol-1 over the “syn” conformation that is preorga- amorphous solvation sphere provided by the solvent to
nized for anion binding. The ability of the unbound acyclic another provided by the aryl triazole host. The nonspecific
host to “relax” into more stable, anti conformations might nature of the binding suggests that favorable contacts pro-
therefore be expected to contribute up to 5-6 kcal mol-1 of vided by the preorganization of a macrocyclic triazole-con-
stability to the unbound state of 2 versus the macrocyclic taining host are unlikely to account for the increased affinity
host (∼2 kcal mol-1 for each of three sequential triazole observed in those receptors and, together with the magnitude
pairs). The actual contribution due to such conformational of the difference in binding constants between the rigid and
relaxations to the free energy of the unbound state might be flexible hosts, suggests that a significant fraction of the
either higher or lower than this crude estimate, depending on binding affinity of macrocyclic hosts arises from the desta-
entropic penalties and interactions between nonadjacent bilization of their unbound state relative to that of the
triazoles, but it demonstrates that enforced dipolar repulsion flexible analogues. Finally, fluoride ion is observed to cata-
in the unbound macrocycle is capable of making up the lyze proton/deuteron exchange between the host triazoles
difference between the observed differences in binding con- and d6-acetone in a process that appears to be mediated by
stants and those expected on the basis of purely entropic the formation of HF2-. The proton transfer reactions are
grounds. Finally, the induced chemical shifts, δmax, whose inhibited by the presence of host that apparently sequesters
correlation to the strength of individual interactions has been fluoride ion.
discussed above, are greater for the acyclic rather than the
macrocyclic hosts, suggesting that, if anything, the flexibility Experimental Section
of the linear oligomers facilitates rather than inhibits favor-
The synthesis and characterization of aryl-1,2,3-triazole oli-
able CH-anion contacts. While a quantitative breakdown gomers 1a,b, 2, and 3 have been reported previously.8 1H NMR
of the contributions from these competing mechanisms is not titration experiments were carried out with the correspond-
within the scope of this work, this analysis may be useful in ing tetrabutylammonium salts of bromide, hydrogen sulfate,
the design of future triazole-based receptors. iodide, nitrate, benzoate, and hexafluorophosphate.
1
H NMR Titrations. Host oligomer concentrations were kept
Conclusion to 1 mM by weighing out appropriate amounts of host and
dissolving in either 500 L or 1 mL of deuterated solvent. These
The 1:1 binding affinities of short, oligomeric aryl-1,2,3- stock solutions were diluted to 1 mM concentrations in 2 mL
triazoles for various anions have been investigated in multi- samples by pipet. Weighing an appropriate amount of the
ple solvents. Over much of the series, the strength of the respective tetrabutylammonium chloride salt and dissolving in
J. Org. Chem. Vol. 74, No. 23, 2009 8933
11. JOC Featured Article Juwarker et al.
1 mL of the 1 mM host solution yielded chloride stock solutions. in 1,2 dichloroethane, which was arbitrarily assigned the value
Subsequent additions of anion from this stock solution enabled of 100. This empirical solvent parameter can be mathematically
the host oligomer concentration to remain constant throughout described by the following relationship:
the titration experiments, with the only possibleperturbation of acceptor number ðANÞ ¼ ½δcorr- =δcorr ðEt3 PO-SbCl5 ÞŠ Â 100
concentration coming from evaporation of deuterated solvent. ¼ δcorr  2:348
Anion was added sequentially to an initial 600 L volume of the
host by micropipet, and 1H NMR of the solution was recorded The acceptor numbers are dimensionless numbers describing
with chemical shifts of the 1,2,3-triazole CH proton recorded the acceptor property of a given solvent relative to those of
versus d6-acetone (2.05 ppm). SbCl5.21,23a
Acceptor Number of Binary Solvent Mixtures. The Gutmann
acceptor number (AN) of a solvent gives a quantitative measure
of the solvent’s ability to accept negative charge (for example, Acknowledgment. H.J. and J.L. contributed equally to
through hydrogen bonding). Acceptor numbers were derived by this work. We thank Duke University and NSF (CHE-06-
Gutmann and co-workers as empirical quantitites for charac- 46670) for support. J.L. was supported by a NSF IGERT
terizing the electrophilic properties of electron pair acceptor and the Schering-Plough Fellowship from the ACS Divi-
solvents. These unitless numbers are obtained from the relative sion of Organic Chemistry, and K.K. was supported by a
31
P NMR chemical shifts produced by the electrophilic actions
Gordon Research Fellowship from Duke University. The
of acceptor solvents (A) in triethylphosphine oxide, described
below: participation of E.Z., J.C., and S.K. was supported through
an introductory research seminar at Duke: CHEM 26S.
NMR facilities were supported by NCBC Grant 2008-IDG-
1010.
The relative 31P NMR chemical shift values δcorr (n-hexane as Supporting Information Available: Additional spectra, ti-
reference solvent, arbitrarily assigned 0) are related to those of tration data, and binding constant fits. This material is available
the 1:1 complex Et3PO-SbCl5 (δcorr(Et3PO-SbCl5)) dissolved free of charge via the Internet at http://pubs.acs.org.
8934 J. Org. Chem. Vol. 74, No. 23, 2009