Acetaminophen

Acetaminophen
Acetaminophen (AAP) which broadly used as an antipyretic and analgesic drug is one reason for
hepatotoxicity in humans and experimental animals at high doses(32). The toxic metabolite of APP
that produced in liver by the cytochrome P450 pathway is named NAPQI(6) that conjugated with
glutathione for excretion in the urine. The AAP overdose cause to glutathione depletion that leads to
NAPQI accumulation and mitochondrial dysfunction(33). Glutathione depletion promotes the tumor
necrosis factor alpha (TNFα) that leads to production of oxygen free radicals from NADPH oxidase
and hepatotoxicity finally(34). The AAP is a potential trigger of cytochrome P450 that induced the
high reactive quinone–imine production. This matches with sulphahydryl groups in proteins and
result in rapid depletion to intracellular glutathione(35). Generally, one parts of the potential
intracellular antioxidant defensive system is glutathione that consumes the singlet oxygen,
superoxide and hydroxyl radicals(36). Enhancing of intracellular flux of oxygen free radicals results
from glutathione depletion leads to oxidative stress in hepatocytes(36). The increasing the serum
levels of GOT, GPT and ALP have been attributed to the structural integrity hepatic damage(37). In
liver tissue, GOT and GPT are located in cytosol and mitochondria. In following of liver damage,
hepatocyte transport function disturbed ... Show more content on Helpwriting.net ...
Main compounds of the enzymatic antioxidant system are three, namely, SOD, CAT and tT which
have an important role in detoxifying of H2O2 and superoxide anion in cells. Ample of hepatotoxic
drugs induces the liver damage by lipid peroxidation indirectly or directly. The proxy radicals are
main factors that mediate lipid peroxidation leading to liver injury and kidney damage(41). MDA as
a main reactive aldehyde appears during polyunsaturated fatty acid peroxidation in the biological
... Get more on HelpWriting.net ...

Synthesis Of Hexane Lab Report
The purpose of this lab is to gain a greater understanding of the reactions between aldehydes and
amines and of their usefulness in synthesis and biology.The lab is divided into 3 steps, the first step
is imine formation, second step is reduction of the imine, and the last step is acylation of the imine.
The imine formed is a primary imine, the first two steps of the lab make up reductive amination1.
The formation of the imine is carried out by adding 0.213 grams of ortho–vallin, the aldehyde, and
.150 grams of para toluidine. The solids were grinded until homogenous, one layer is formed. The
crystals went from brown to orange liquid layer. The bi–product of imine formation is water, and
OH gets protonated and come off during the reaction. Recrystallization is done to get rid of water.
Hexane is used as the recrystallization solvent because it is non–polar, like the imine. The mass is
0.3365 grams and the percent yield is 99.6%. There was some product lost on the stirring rod. The
IR showed a peak at 2942.40 indicating a methyl group and a peak at 1593.67 and 1614.90 ... Show
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Sodium borohydride is a reducing agent that reduces double bonds. The solution went from orange
then to a cloudy white precipitate. The bright orange in the first step is because of imine formation.
Lack of colour, after the addition of NaBH4, shows imine is no longer there it has been reduced.
That amine is now formed evident by the white precipitate. Sodium Borohydride is highly reactive,
so it needs a protic solvent like ethanol to help stabilize. This is why ethanol is added before the
sodium borohydride. The formation of imine happens at acidic conditions and ethanol makes sure
the solution does not get to acidic otherwise amine is not formed. Sodium borohydride is waited to
be added, because if added before the imine is formed it reduces the intermediate and not the imine

Cooperative Cation Binding Catalysis For Direct Generation...
Abstract In this study, the concept of cooperative cation binding catalysis was elegantly applied for
direct generation of two contiguous tertiary and quaternary stereogenic centers. Using a highly
accessible chiral oligoethylene glycol (oligoEG) as a cation–binding catalyst, asymmetric Mannich
reaction of α–thiocyanato cyclic ketones as Mannich donors was performed with α–amido sulfones
as the bench–stable imine precursors in the presence of potassium fluoride as the base, affording α–
thiocyanato–β–amines possessing tetra–substituted C–SCN centers. The salient features of this
process include (a) a transition–metal free and operationally simple procedure, (b) direct use of α–
amido sulfones as bench–stable precursors of sensitive imines, ... Show more content on
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In particular, chiral compounds with β–amino–α–thiocyanate moieties are rarely explored in the
medicinal chemistry area because of their synthetic difficulty,[5] although they are versatile
precursors for the synthesis of β–aminothiols,[6] β–aminosulphonic acids,[7] and 2–
iminothiazolidines,[8] present in some stereoselective catalysts, and many biologically and
pharmacologically active compounds. To the best of our knowledge, only three related publications
have been reported to date.[9,10] In 2013 Sala et al.[10a], and Babu and Parquette[10b]
independently reported the asymmetric synthesis of β–amino–α–thiocyanate compounds via the
desymmetrization of meso–aziridines with TMSNCS using combined Ca(II)/Mg(II) VAPOL
phosphate salts and chiral dimeric yttrium–salen complexes as catalysts. Quite recently, Nakamura
et al. also reported the same transformation using chiral imidazoline−phosphoric

Acts : Discussion : Artemisinin-Based Combination Therapies
Discussion Artemisinin–based combination therapies (ACTs) are currently considered gold standard
in the management of uncomplicated malaria. For the liver stages, primaquine is the only drug
approved to eliminate hypnozoites. Resistance against existing antimalarials is well documented,
and troubling due to the emerging resistance to artemisinins. Therefore, a rising incidence of drug
resistance requires the development new drugs, with novel disease targeting strategies. Moreover,
the challenge is to develop innovative drugs that demostrate (i) faster onset and longer duration of
drug action, (ii) safe for children and pregnant women, and (iii) ideally be amenable to a single–dose
administration. Following are brief descriptions of such ... Show more content on Helpwriting.net ...
Ferroquine, unlike chloroquine, accumulates in the digestive vacuole of the chloroquine resistant
parasites, enabling P. falciparum chloroquine resistance transporter, PfCRT inhibition. [6] 3.
Amodiaquine is also active against most chloroquine resistant strains, however, two reactive
metabolites are formed, namely imine and aldehyde, and are the likely cause of the hepatotoxicity
and agranulocytosis, respectively. [7] 4. N–tert–Butyl isoquine (GSK369796) was designed to avoid
the formation of quinone imines, and has entered Phase I studies. It is potent in vitro, including in
the chloroquine resistant strain K1 (EC50 = 13 nM) and is active in vivo with an ED50 = 3.8
mg/kg/day, thus being comparable to amodiaquine. In spite of the excellent exposures and near
quantitative oral bioavailabilities in animal models, its development was discontinued due to
exposures insufficient to demonstrate drug safety superior to chloroquine. [8] 5. In an effort to select
the next generation of quinoline methanol derivatives that could serve as a replacement for
mefloquine, the Walter Reed Army Institute of Research screened for analogs with a lower brain
penetration, and identified WR621308, which has a substantially lower permeability across MDCK
cell monolayers than mefloquine, suggesting lower brain exposures. [9] 6. Cycloguanil and
pyrimethamine demonstrate inhibition of dihydrofolate reductase (DHFR).

The First Utilized Schiff Bases 3a K Towards Mild Steel
3. Results and discussion 3.1. Identification of inhibitors In the view of the aforementioned
remarked values of inhibition efficiency of this class of organic inhibitors, this paper aims to study
the concerned function of the first utilized Schiff bases 3a–k towards mild steel in 0.5 M H2SO4
solution. N–aryl– (Sb_a–g), N–heteryl– (Sb_h–j)–, and the Schiff base Sb_k have been obtained
condensation of N–aminophthalimide (S) with the corresponding aromatic aldehydes 2a–e,
heterylaldehydes 2f–j and isatine 2k, respectively. This study takes into account the beneficial role
that could be played by the p–electrons of the heterocyclic aldehyde or ketone N– and O– atoms
present in the heterocyclic aldehyde and ketone moieties. The name of products and symbols were
listed in Table 2. The melting point, yield, time of reaction and IR spectra of products were listed in
Table 3. Spectral study has been used to characterize the structure of the novel synthesized Schiff
bases (Sb_f–k) which to our knowledge have not been previously reported as shown in Table 4. The
structure of the Schiff bases Sb_a–e was confirmed by identity of melting point and spectral data in
the literature 25–27. The infrared spectra all the products Sb_a–k revealed that no coupling bonds in
the 3 Mm region that refers to the absence of the amino –NH2 functionality of compound S instead
a sharp absorption band appears on the region of 1604–1688 cm–1. Characteristic to the imino –
c=N– group, indicating that compound

Organic Silica Modified Membranes Based On Organic /...
In this study, we describe a versatile strategy to fabricate newly–fashioned silica–modified
membranes based on organic/inorganic hybridization for oil/water emulsion separation. The silica–
modified membranes were easily obtained by a simple two–step immersion of polysulfone hollow
fiber membranes into silicon solution of tetraethyl orthosilicate mixed with 3–
glycidyloxypropyltrimethoxysilane, and subsequently into lactic acid solution. Attenuated total
reflectance Fourier transform infrared spectroscopy, X–ray photoelectron spectroscopy, and field
emission scanning electron microscopy were used to characterize the compositions and structures of
the membranes. A micronanoscaled SiO2–based coating was generated roughly and continuously on
... Show more content on Helpwriting.net ...
Introduction
In recent years, because of increasing environmental pollution resulting from the sustainable
development of society, a large volume of oily wastewater generated from a variety of effluents and
domestic sewage has become one of the most serious problems that severely threaten the ecological
balance worldwide []. Hence, the treatment of oily wastewater with minimum environmental impact
needs to be performed urgently. Conventional methods such as gravity separation, flotation,
coagulation, skimming flotation, and flocculation implemented in industry are severely limited by a
low separation efficiency, high operation cost, and secondary pollution []; these traditional
techniques failed to cope with finely dispersed emulsions with very small size oil droplets in
micrometer or sub–micrometer, even several nanometers range []. As an energy–efﬁcient and
environmentally friendly separation medium, membrane filtration technology has incited
considerable attention for a certain period of time and been proven as a promising method in the
separation of oil–in–water emulsion []. This phenomenon could be rationalized partially by the
principle that membrane filtration would first demulsify the emulsion and then filter it []. However,
the largest challenge was the severe fouling issue, because of the adsorption and/or penetration of oil
droplets onto the membrane surfaces and/or into the membrane

Diels Alder Reaction Lab Report
Organic Chemistry–Diels Alders Reactions Introduction Diels–Alder reactions are organic chemical
reactions which involve [2 + 4] cycloaddition. The cycloaddition takes place between the conjugated
dienes and the substituted alkenes (dienophiles). This interaction between the dienophiles and
conjugated dienes result in the formation of substituted cyclohexene system. In 1928, two scientists
(Kurt Alder and Otto Diels) jointly invented Diels–Alder reaction. This invention enabled them to
receive the award (Nobel Prize in Chemistry) in 1950. Diels–Alder reactions are used in organic
chemistry to prepare compounds with 6–membered systems. Diels–Alder reactions are also
fundamental in the synthesis of compounds with TT systems like imines and carbonyls. The
application of Diels–Alder reactions in TT systems leads to the formation of heterocycles in a
reaction referred to as the hetero–Diels–Alder reactions. In some specific conditions, Diels–Alder
reactions are reversible. The reversible Diels–Alder reactions are called the retro–Diels–Alder
reactions. Diels–Alder ... Show more content on Helpwriting.net ...
The dienes are capable of containing various substituents. Though, Diels–Alder reactions only
proceed when dienes are in s–cis conformation. However, the Diels–Alder reactions can proceed
when the butadienes are in s–trans conformation. The dienophiles contain 'masked functionality,' for
example; the dienophiles participate in Diels–Alder reaction with the dienes inserting 'masked
functionality' onto the resultant molecule. Several reactions occur to transform this 'masked
functionality' into a suitable group. The dienophiles can take part in Diels–Alder reactions by either
'normal demand' or 'inverse demand' Diels–Alder reaction. In 'normal demand,' Diels–Alder
reactions, the dienophiles contain electron–withdrawing group conjugated to the alkenes. In inverse
demand, the electron–donating group is in conjugation with

The Rate Of Aggregation, Differential, Sedimentation, And...
4. NEED FOR STABILISATION Although the small size of nanocrystals leads to several
advantages, but at the same time, it can lead to stability concerns as well. Theoretically, if we
increase the drug surface area, it leads to an increase in Gibbs free energy. The system tries to
reverse this increase by agglomeration/aggregation, ultimately leading to increased particle size and
reduced stability. Principally, the literature describes three mechanisms for aggregation–prekinetic
aggregation, differential sedimentation and orthokinetic aggregation. In any dispersion, the particles
are in continuous Brownian motion, and they may collide and stick together as a result of the
attractive forces between them. Such a mechanism for aggregation is known as prekinetic
aggregation. The rate of aggregation in such cases would be determined by the frequency of
collisions as well as the chances of cohesion during collision. Differential sedimentation assumes
importance when particles of varying sizes and densities settle in a suspension. Faster settling
particles collide with the slower moving ones, thereby resulting in aggregation. Lastly, the
orthokinetic aggregation mechanism describes the aggregation brought about by increased particle
collisions, arising out of particle transportation as a result of fluid motion. Orthokinetic aggregation
depends upon initial particle size and velocity gradient, but is independent of temperature. Apart
from aggregation, another stability issue

Paracetamol Research Paper
Paracetamol (Acetaminophen) hepatotoxicity is the classical example of direct liver injury.
Paracetamol is generally safe at recommended doses, but its intrinsic toxicity at higher doses
represents the most important cause of acute liver failure and transplantation. Paracetomol is rapidly
metabolized in the liver at therapeutic doses principally through sulfation and glucuronidation, and
only very small portion is oxidized by cytochrome P450 2E1 to generate a highly reactive and
cytotoxic intermediate N–acetyl–p–benzoquinone imine (NAPQI), which yields a harmless water–
soluble product, mercapturic acid on conjugation by hepatic glutathione. However, the capacity for
glucuronidation and sulfation is exceeded after acetaminophen overdose and a large amount of
NAPQI is formed via cytochrome P450 2E1 [26, 27]. After a toxic dose of acetaminophen, total
hepatic GSH (Glutathione) is depleted by as much as 90%, and as a result, the metabolite covalently
binds to cysteine groups on protein, forming acetaminophen–protein adducts .This mechanism is
shown in figure 2. After administration of paracetomol, heptotoxicity was noted at 500 mg/kg, orally
when administered for 2 weeks in rats [28, 29]. 2.3. Azathioprine (AZA) ... Show more content on
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AZA is a prodrug that is cleaved in vitro to 6–Mercaptopurine (6‑MP) non‑enzymatically primarily
by GSH and its imidazole derivative by glutathione in the liver, which is further metabolized to 6–
MMPN and 6–TGN [30]. AZA toxicity to rat hepatocytes was preceded by depletion of GSH. In
hepatocytes, GSH is consumed during metabolism of AZA to 6‑MP. The mechanism of AZA
toxicity is shown in Figure. 3. It has been reported that the administration of AZA (15 mg/kg orally)
for 4 weeks induced hepatotoxicity in rats

Advantages And Disadvantages Of Acetaminophene
Acetaminophen (APAP) is one of the most commonly used analgesic and antipyretic drugs
worldwide and easily available for use without a prescription. In 2014, over 67,000 people receive
an overdose of APAP in the US, among which around 1,200 cases ended with severe liver failure or
death [1].
Over the past two decades, considerable effort has been made to understand the mechanisms of
APAP hepatotoxicity. Although the complex molecular mechanisms remain speculative, several
theories have been proposed to explain APAP–induced hepatotoxicity. During metabolism, around
5–10% APAP is biotransformed into a highly reactive metabolite, N–acetyl–p–benzoquinone imine
(NAPQI), by several cytochrome P450 enzymes (CYPs) [2]. Normally, hepatic glutathione ... Show
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Among these cell lines, human hepatocarcinoma cells (HepG2), an easy–to–handle and inexpensive
cell model, is one of most frequently used cell lines in hepatotoxicity studies. HepG2 cells, which
are isolated from a hepatoblastoma, exhibit many genotypic characteristics that are crucial for
toxicity responses [11, 12]. Indeed, these cells express a low level of CYP2E1, but the expression of
other CYPs playing essential roles in APAP metabolism (such as CYP1A1, CYP1A2, and CYP3A4)
are comparable with other more metabolic competent human hepatic models, such as HepaRG and
primary human hepatocytes (PHH) [13]. CYP2E1, exclusively located in the endoplasmic reticulum
(ER) as well as mitochondria, is an effective ROS generator in cells during catalyzing APAP
metabolism to NAPQI [14, 15]. Therefore, HepG2 cells, which has a minimal level of CYP2E1–
induced ROS formation, could be a useful model to study the contribution of non–CYP2E1–
mediated mitochondrial–specific oxidative stress in APAP–induced hepatic injury. In fact, the
CYP2E1 expression and enzyme activity vary substantially in both non–compound–exposed and
compound–exposed liver slices obtained from human donors [16, 17]. Moreover, genetic variation
of CYP2E1 (CYP2E1*5, *1B and *1D), which have been associated with

Fuctose-Bisphosphate Aldolase Lab Report
Fructose–bisphosphate aldolase
Table 1 Alternative name, co–factors and reaction summarize in this table
Accepted Name: Fructose–bisphosphate aldolase.
Alternative Name(s):
Aldolase.
D–fructose–1,6–bisphosphate D–glyceraldehyde–3–phosphate–lyase.
Fructose–1,6–bisphosphate triosephosphate–lyase.
Reaction catalyzed: D–fructose 1,6–bisphosphate glycerone phosphate + D–glyceraldehyde 3–
phosphate
Cofactor(s): Zn(2+).
Introduction Fructose–bisphosphate aldolase is a glycolytic compound. It catalyzes the reversible
aldol cleavage or buildup of fructose–1,6–bisphosphate into dihydroxyacetone–phosphate and
glyceraldehyde 3–phosphate. This enzyme has been divided in two classes of fructose–bisphosphate
aldolases based on distinctive reactant ... Show more content on Helpwriting.net ...
Either the carbon–carbon bond cleavage or the arrival of glyceraldehyde–3–phosphate involve the
moderate stride of the catalysis response; on the other hand, studies show that the GAP discharge is
likely the slowest step.
It has been demonstrated that aldolase is restrained allosterically by oxidized glutathione, which is
an oxidizing specie. The glutathione oxidizes a thiol 25 angstroms from the synergist site, which
along these lines causes a drop in reactant action. Furthermore, the compound demonstrates no
positive cooperativity, regardless of being an oligomer. Indeed, energy information really
demonstrate that the compound displays negative cooperativity. Along these lines the catalysis is
profoundly compartmentalized inside of every subunit and tying causes minimal distal change of the
chemicals structure.

Corrosion And The Corrosion Of Mild Steel
N–aminophthalimide as synthon for heterocyclic Schiff bases: Efficient utilization as corrosion
inhibitors of mild steel in 0.5 mol.L–1 H2SO4 solution
Mohamed M. Abdelaal [a]*, Y.F. Barakat [a], Hamed A. Y. Derbala [b], Hamdy H. Hassan [b]
[a] Tabbin Institute for Metallurgical Studies, P.O. Box 109 Helwan, Cairo, Egypt.
[b] Chemistry Department, Faculty of Science, Ain Shams University, Abbasiya, Cairo, Egypt,
11566.
*Corresponding author: E–mail address: chemtims@yahoo.com
Abstract
Many Schiff bases, including two novel compounds, were prepared to inhibit the corrosion reactions
of mild steel in acidic medium. Their chemical structures were determined using IR, Mass
spectrometry and 1HNMR spectroscopic analysis. The results showed that the protection of mild
steel, by these Schiff bases, depends on many factors like function group, inhibitor dose and the
temperature of the medium. Thermodynamic adsorption parameters (Kads, ΔGads) of studied
inhibitors were calculated using the Langmuir adsorption isotherm. The presence of iodide ions in
the medium increased the efficiency of these inhibitors. AC impedance spectroscopy was used to
determine the polarization resistance. The scanning electron microscopy (SEM) showed the
corrosion products decreased after using these inhibitors. In addition, the best inhibitor in this study
used to increase corrosion inhibition of treated sample by Electrolytic plasma process (EPP).
Key words: N–aminophthalimide; Schiff bases; Mass

Dna Essay
2.10 binding analysis of investigated complexes with Calf thymus DNA (CT–DNA)
2.10.1 Viscosity for DNA in the presence investigated complexes
Oswald micro‐viscometer was used for measuring the viscosity of investigated complexes at
constant temperature 25 oC. With maintaining the concentration of CT–DNA constant (420 uM), the
Fluidity times were registered for different concentrations of investigated complexes (0 – 250 μM)
[13,16,19,20,26,27,28,29,30,34,39]. Bubbling nitrogen gas is used for mix the solution through the
viscometer. Viscosity for DNA in the presence investigated complexes was determined from the
mean value of the three of readers. ηo is relative viscosities for DNA with investigated complexes
and estimated from the ... Show more content on Helpwriting.net ...
The investigated complexes were dissolved in DMF solvent. Electronic spectra experiments were
performed by keeping investigated complexes concentrations constant while changing the CT–DNA
concentration in the interaction medium. The absorption due to free CT–DNA was eliminated by
adding a proper amount of CT–DNA to both compound solution and the reference solution and the
spectra data obtained were considered to result from the DNA–metal complex aggregation. From the
electronic spectra data, Kb (the intrinsic binding constant) was estimated from plotting [DNA] /(εa –
εb) versus [DNA] according to the following relation :
([DNA])⁄((ε_a–ε_f))=[DNA]1/((ε_b–ε_f))+1/K_b 1/([(ε_b–ε_f )]) (16)
Where [DNA] is the molar concentration of CT–DNA in base pairs εf, εa and εb are the extinction
coefficients of free, apparent and fully bound complex, respectively. εf and εa were estimated from
the isolated metal complex calibration curve Aobs / [complex] and DNA calibration curve Aobs /
[DNA], respectively. Kb was calculated from the ratio of slope to intercept where a slope is equal to
1/(εb – εf) and y– intercept is equal to 1/Kb (εb – εf) from this plot. ∆G_b^≠ (the standard Gibb,s
free energy) for DNA binding was calculated from the following equation
[13,16,19,20,26,27,28,29,30,34,39]:
∆G_b^≠=–RT LinK_b (17)
2.11 Molecular docking
Dell Precision™ T3600 Workstation [Intel Xeon E5–1660

The Drug Development And Approval Process
As mentioned in class, as well as in the required Krishna (2008) article, the drug development and
approval process is an extensive and costly endeavor. The goal of experimental medicine is to
increase the efficiency of drug development by providing a better understanding of the drug's
mechanism(s) of action, dose response, efficacy, and safety, allowing the process to be accelerated
for the most promising and efficacious candidates (Krishna, Herman, & Wagner, 2008). Preclinical
testing begins with identifying the ideal drug target. The target should be disease–modifying and/or
have a proven function in the pathophysiology of the disease. Target expression should not be
uniformly distributed throughout the body. There should also be a favorable IP condition allowing
the drug freedom to operate without competition. If the druggability is not obvious a 3D–structure
for the target protein or a close homologue should be available for assessment. The target should
also have favorable 'assayability' enabling high throughput screening. To identify these targets there
are many strategies that can be utilized such as: genomic analysis (phenotype analysis, genetic
association, gene expression profiling etc.), pathway analysis, and activity based proteomic profiling
(Frank & Hargreaves, 2003; Lipsky & Sharp, 2001; Krishna, Herman, & Wagner, 2008). After
conducting extensive animal studies in the laboratory and assessing the safety and biological activity
of the drug compound, the

Artemisinin Based Combination Therapies ( Acts )
Artemisinin–based combination therapies (ACTs) are currently considered gold standards in the
management of uncomplicated malaria. For the liver stages, primaquine is the only drug approved to
eliminate hypnozoites. Resistance against existing antimalarials is well documented, and troubling
due to the emerging resistance to artemisinins. Therefore, a rising incidence of drug resistance
requires the development new drugs, with novel disease targeting strategies. Moreover, the
challenge is to develop innovative drugs that demostrate (i) faster onset and longer duration of drug
action, (ii) safe for children and pregnant women, and (iii) ideally be amenable to a single–dose
administration. Following are brief descriptions of such innovative ... Show more content on
Helpwriting.net ...
2. Ferroquine was found to be active against chloroquine– resistant strains, and is currently
undergoing Phase II clinical trials. Ferroquine, unlike chloroquine, accumulates in the digestive
vacuole of the chloroquine resistant parasites, enabling P. falciparum chloroquine resistance
transporter, PfCRT inhibition.
3. Amodiaquine is also active against most chloroquine resistant strains, however, two reactive
metabolites are formed, namely imine and aldehyde, and are the likely cause of the hepatotoxicity
and agranulocytosis, respectively.
4. N–tert–Butyl isoquine (GSK369796) was designed to avoid the formation of quinone imines, and
entered Phase I studies. It is potent in vitro, including in the chloroquine resistant strain K1 (EC50 =
13 nM) and is active in vivo with an ED50 = 3.8 mg/kg/day, thus being comparable to amodia–
quine. In spite of the excellent exposures and near quantita– tive oral bioavailabili ties in animal
models, its developmen t was discontinue d due to exposures insufficient to demonstrate drug safety
superior to chloroquine.
5. In an effort to select the next generation of quinoline methanol derivatives that could serve as a
replacement for mefloquine, the Walter Reed Army Institute of Research screened for analogs with a
lower brain penetration, and identified WR621308, which has asubstantially lower permeability
across MDCK cell monolayers than mefloquine, suggesting lower brain

As mentioned in class, as well as in the Krishna (2008) article, the drug development and approval
process is an extensive and costly endeavor. The goal of experimental medicine is to increase the
efficiency of drug development by providing a better understanding of the drug's mechanism(s) of
action, dose response, efficacy, and safety, allowing the process to be accelerated for the most
promising and efficacious candidates (Krishna, Herman, & Wagner, 2008). Preclinical testing begins
with identifying the ideal drug target. The target should be disease–modifying and/or have a proven
function in the pathophysiology of the disease. Target expression should not be uniformly
distributed throughout the body. There should also be a favorable IP condition allowing the drug
freedom to operate without competition. If the druggability is not obvious, a 3D–structure for the
target protein or a close homologue should be available for assessment. The target should also have
favorable 'assayability' enabling high throughput screening. To identify these targets there are many
strategies that can be utilized such as: genomic analysis (phenotype analysis, genetic association,
gene expression profiling, etc.), pathway analysis, and activity–based proteomic profiling (Frank &
Hargreaves, 2003; Lipsky & Sharp, 2001; Krishna, Herman, & Wagner, 2008). After conducting
extensive animal studies in the laboratory and assessing the safety and biological activity of the drug
compound, the

Competency Inventory
Functional Competency Inventory and Design by Jai Cortes
I. Title of the Diagnostic Tool: Functional Competency Inventory and Design
II. Overview of the Diagnostic Tool
a. Definition
In a nutshell, functional competency inventory and design, is a tool which aims to measure the
competencies of functional groups of organizations, which are affected by their respective core
objectives. In 1973, McClelland supported "testing for competence, rather than intelligence." By
definition, competencies are "general descriptions of the abilities necessary to perform successfully
in areas specified. Competency profiles synthesize skills, knowledge, attributes and values, and
express performance requirements in behavioral terms. The review of ... Show more content on
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Unlike Core Competency Inventory and Design, Functional Competency Inventory and Design
focuses on and measures the competency (knowledge, skills, personal attributes, and behavior) of
functional groups. "These groups are based on organization 's structure and are the formal groups on
organizational charts. These groups have their tasks and leaders chosen by higher management.
Functional groups usually have specific rules of operation and clearly defined superior–subordinate
relationships." For example, in the school setting, the Head Registrar is the designated leader of a
functional group of subordinates that includes a number of assistant registrars, liaison officer, and
secretaries.
What Functional Competency Inventory and Design does is that it measures the competency
required for each functional area, as like in the above mentioned example, the Registrar's office, and
checks whether the members of the group has the competency required for the functional area.
Another way of seeing functional groups would be to see that these functional groups are equivalent
to departments in companies. So Finance, Marketing, Operations, Research and Development, and
other departments of the corporation are all functional groups, whose competency can be measured
through this

Global Market For Sun Care Products
A. Background Significance
Global Market for Sun Care Products
The global market for sun care products is expected to reach US $11.1 billion by 2020. While
current sunscreen agents in the market protect against UVA and/or UVB rays, offering important
protection from sunburn, photo aging, and DNA damage, these options can come with serious
negative impacts on our health and the environment (2–5).
Mycosporine
Mycosporines & mycosporine–like amino acids (MAAs) are UV absorbing (λmax= 310 to 360 nm),
small (<400 Da), colorless, water–soluble molecules that are synthesized by a variety of micro–
organisms (e.g. aquatic fungi, eukaryotic algae, and cyanobacteria (1) and can get ingested by
marine animals. Mycosporine and MAA structures consist of one or two modified amino acid
residue(s) linked to a cyclohexenone core through imine linkages. Their conjugated system structure
allows for them to screen UV rays and dissipate the energy as heat without generating free oxygen
radicals. In addition, MAAs are known to provide additional protection from oxidative, osmotic and
thermal stress. Due to the growing global market for sun care products and increasing consumer
interest towards natural and environmentally conscious products, MAAs are great candidates for
commercialization in the pharmaceutical and cosmetic industries. For instance, shinorine is used as
an active ingredient in sunscreen cream Helioguard 365, and is prepared through liposomal
encapsulation of dried P. umbilicalis

Aromaticity And Reactions Of Pyridine
Aromaticity and reactions of pyridine Introduction
The structure of pyridine e considerably resembles that of benzene. It may be formally derived from
the structure of benzene through the exchange of one ring carbon for a nitrogen but, is pyridine
which is structurally and electronically allied to benzene, also aromatic?. Pyridine is aromatic based
on the following facts. The protons of pyridine show chemical shifts in the NMR spectrum that are
ordinary of aromatic protons. Furthermore, electrophilic substitutions at pyridine are possible. The
nitrogen of pyridine is sp2–hybridized and possesses one lone electron pair. This electron pair is
located in an sp2 orbital that is parallel to the ring plane. Therefore, in contrast to pyrrole, the
nitrogen 's lone electron pair of pyridine doesn 't take an interest in the aromatic π electron system.
As a result, pyridine can easily be protonated, yielding a pyridinium cation. Two valence electrons
of the nitrogen are included in the two (σ bonds) with the adjacent carbons. The fifth valence
electron of the nitrogen occupies the p orbital that is perpendicular to the ring plane. Thus,
analogous to the ring carbons, this electron takes part in the π electron system. Com¬par¬i¬son of
ben¬zene and pyri¬dine.
Electrophilic substitutions at pyridine
As an aromatic compound, pyridine may participate in electrophilic substitutions as an electrophile.
How easily and at which positions do these substitutions occur? In order to answer

Imine Synthesis Lab Report
The underlying principles of the imine synthesis reactions include isomerization, pH values, and the
importance of acids as catalysts. Imine formation begins with either an alkene or aldehyde that then
produces alkenes isomers.7 Imine formation generally produces a mixture of products with E or Z
conformation. This conformation is more commonly denoted as cis or trans. The trans product, or E,
forms when the highest priority groups are on opposite sides of the alkene double bond, which is the
more stable of the two conformations due to a lack of steric interaction wherein the molecules are
more separated allowing for free rotation about the double bond. In contrast, the cis, or Z, alkene
occurs when the highest priority groups are on the same side of the double bond, but the energy is
not evenly distribution in the molecule, ... Show more content on Helpwriting.net ...
Using TLC analysis, the purity and polarity of the reaction mixtures were analyzed to determine the
sample used to obtain the IR and 1H NMR spectrums of the product. IR and 1H NMR spectroscopy
was used to characterize each molecule by determining functional groups present based on peak
identification and hydrogen positional characteristics in the molecules respectively. Melting point
analysis was also used to further understand and characterize the reaction mixtures with comparison
to literature values confirming its molecular structure. Reaction mixture 1 containing the molecular
sieves was found to be the purest and most polar of the three compounds as determined by TLC
analysis and spot location as it was the closest spot towards the bottom of the plate. Each compound
was characterized by four molecular motions observed IR and 1H NMR as identified by the multiple
functional groups present in the molecules and seen in the graphs

2-Contaminophenol
2. Material and methods
In this investigation, 2–aminophenol(AP), 4–chloroBenzaldehyde(CB), the metal salts
CuCl2.2H2O(99.00%), Pd(OAc)2(99.99%), and AgNO3(99.50%) and Calf thymus DNA(CT–
DNA) were utilized starting chemicals and purchased from Sigma–Aldrich Chemise (Germany).
Agarose was purchased from Fischer– Biotech (GE Heath care). Tracking dye (0.25 % bromophenol
blue, 40 % sucrose, 0.25 % xylene cyanole and 200 mM EDTA) and Ready–load 100 bp DNA
ladder were used as the native size DNA and purchased from Bio labs.
2.1 Synthesis of the investigated bi–dentate CBAP imine ligand The investigated bi–dentate CBAP
imine ligand was synthesized by adding 4–chloro Benzaldehyde(10mmole, 1.40g) dissolved in
absolute ethanol to same moles of 2–aminophenol(10mmole, 1.09 g) dissolved in absolute ethanol.
This mixture was stirred under reflux at 700C for 2 h by using tri–ethyl amine as a catalyst and then
allowed to cool at room temperature to obtain the yellow solid precipitate. This yellow precipitate
was then filtered, washed and dried in vacuo over anhydrous CaCl2 and checked the purity of
synthesized investigated imine ligand by TLC using silica gel G [15,16]. ... Show more content on
Helpwriting.net ...
This mixture was stirred for 1 h and evaporated overnight to obtain the investigated complex. This
formed solid investigated complex was filtered, wash and then dried in vacuo over anhydrous
CaCl2. TLC is used for determining the purity of investigated complex by using silica gel G

Fructose Intolerance And The Aldolase B Gene And Fructose
Fructose Intolerance is caused by mutations in the aldolase B gene and Fructose 1, 6–biphosphate
aldolase. Both are important because it is responsible for gluconeogenesis and fructose metabolism.
Gluconeogenesis is the metabolic pathway that results in the production of glucose from non–
carbohydrate carbon substrates or the opposite of Glycolysis (Figure 1). In simple terms, a mutation
on Fructose 1, 6–biphosphate would both hinder the production of pyruvate and the production of
glucose. Fructose Intolerance is also referred to as Fructose 1–Phosphate Aldolase Deficiency. The
modified enzyme varies in its original function and structure that derived from a restricted genetic
mutation (Cox, O'Donnell, Camilleri, and Burghes).
Aldolase B is classified as a Lyase, or an enzyme that catalyzes the breaking of various bonds means
other than hydrolysis and oxidation. Lyase often forms a double bond or a new ring structure.
Fructose Intolerance is caused by mutations in the aldolase B gene which is expressed in the liver
(Malay, Allen, and Tolan). Its molecular compound is shown in Figure 2 and has two active site
residues, Lysine and Glutamate, as well as several charged residues. The functional assignment is
complex because of the proximity of the many charged amino acids found at the active site. Figure 3
shows where the substitution of Proline for Alanine occur at position 149 (Malay, Allen, and Tolan).
The A149P substitution is known as AP–aldolase (Malay, Procious, and

Acetaminophen Theory
Description of Disease and Underlying theory
Acetaminophen, once ingested into the body is rapidly absorbed from the gastrointestinal tract into
the blood stream where it reaches peak plasma concentration in as little as half an hour. Here, it
circulates around the body for a period of up to 4 hours during which it produces its analgesic and
antipyretic effects before the acetaminophen is metabolised and deactivated by the liver by a
possible 3 pathways: Glucuronidation, sulfation and oxidation (Show below in Figure 2). The most
commonly used pathway is the glucuronidation metabolism, closely followed by the sulfation
pathway. These methods of metabolism deactivate the acetaminophen in the hepatocytes into non–
toxic conjugated sulphate and glucuronide which are excreted in the urine [23] [24]. The majority of
the initially ingested therapeutic dosage is metabolised this way, with the remaining acetaminophen
being metabolised via the third hepatic cytochrome P45 oxidase pathway, primarily by the enzyme
CYP2E1 [25]. When acetaminophen is metabolised via this method, a small amount of a highly
reactive toxic intermediate ... Show more content on Helpwriting.net ...
This is rapidly removed by the liver, by reacting with glutathione stored in the hepatocytes,
conjugating the NAPQI into non–toxic cysteine and

A Brief History Of Alzheimer 's Disease
1. Introduction 1.1 A brief overview of Alzheimer's diseases The life expectancy is now doubled
from the last century in the developed countries due to the revolution progress in medicine and
health mainly to chronic diseases. Alzheimer's disease (AD) is one of the most well–known and
familiar diseases in the modern societies AD was first reported by Alois Alzheimer in 1907.The AD
is the most common type of dementia and a neurodegenerative disease characterized by the damage
of nerve cells in the cerebral cortex. The health statistics report that AD disease affects more than 50
million people worldwide in 2003, it is expected this number to increase to 114 million by 2050.(1)
It is reported that AD disease affect one in three people over the age 85.(2) The symptoms of AD
include depression, apathy, anxiety, agitation, aggression, delusions, hallucinations, wandering, and
inappropriate sexual behaviours.(3) AD patients suffer from decrease in cognitive function and short
term memory. AD is characterised by the formation of insoluble clumps of protein or plaques,
formed by proteins known as β–amyloids. These attach to the cell surface of neurons and disabled
nerve transmission. These plaques have been demonstrated to contain relatively high levels of Zn2+,
Cu2+ and Fe3+ (1 mM, 0.4 mM and 1 mM respectively).(4) While the precise role of these metals is
still uncertain, they appear to bind to so–called β–amyloid peptides that constitute the bulk of plaque
deposits. Cu2+

Compare And Contrast Paracetamol And Aspirin
Compare and contrast the mechanism of action and therapeutic uses of aspirin and paracetamol
Aspirin, also known as acetylsalicylic acid, was among the earliest drugs to be synthesized and is
still commonly used worldwide today. Aspirin is useful as an anti pyretic, anti platelet, analgesic, as
well as, anti–inflammatory drugs. Its main clinical importance now is in the treatment of
cardiovascular disease. It can be orally administered and is rapidly absorbed as the liver metabolizes
75%, but can't be given to human beings under the age of 16. The elimination of aspirins metabolite,
salicylate, follows first–order kinetics at low doses, but at high doses, it follows saturation kinetics.
(Rang et al., 2012).
Paracetamol, also known as acetaminophen, ... Show more content on Helpwriting.net ...
By inhibiting the COX enzyme it controls pain by controlling the signals before they reach the
brain.
The analgesic mechanism of paracetamol has been suggested that the metabolites of paracetamol
such as NAPQI, which act on TRPA1–receptors in the spinal cord, suppress the signal transduction
from the superficial layers of the dorsal horn, therefore alleviating pain.
The exact mechanisms by which COX is inhibited in various circumstances are still being discussed
and this is because of the differences in activity of aspirin, paracetamol and other NSAIDs. With
these differences it has been proposed that further COX enzymes may exist. A theory of how
paracetamol may work is by the inhibition of the COX–3 isoform (a COX–1 splice variant). COX–3
has been expressed in dogs and it shows that this enzyme shares similarities to other COX enzymes,
while producing pro–inflammatory chemicals and is selectively inhibited by paracetamol. But
research has continued and in humans the COX–3 enzyme doesn't show inflammatory action and
paracetamols blockage of it is not significant in its functioning in

As mentioned in class, as well as in the required Krishna (2008) article, the drug development and
approval process is an extensive and costly endeavor. The goal of experimental medicine is to
increase the efficiency of drug development by providing a better understanding of the drug's
mechanism(s) of action, dose response, efficacy, and safety, allowing the process to be accelerated
for the most promising and efficacious candidates (Krishna, Herman, & Wagner, 2008). Preclinical
testing begins with identifying the ideal drug target. The target should be disease–modifying and/or
have a proven function in the pathophysiology of the disease. Target expression should not be
uniformly distributed throughout the body. There should also be a ... Show more content on
Helpwriting.net ...
The main goal in Phase I is to find out if the investigational new drug is safe. In this first phase of
human testing, testing determines the correct dosing and exposes the most common side effects. If
the investigational new drug is found to be safe, Phase II of human testing can begin. The main goal
of Phase II is to find out if the investigational new drug is effective. Unlike in Phase I, the patients
tested in Phase II are not healthy. In this phase, testing determines whether the drug works on
patients it was designed to help. Results are obtained by comparing the group of test patients to
other groups taking a different drug or taking a placebo. Phase III is the first large–scale trial of
human testing. This phase can only begin if the new drug shows to be effective in the phase II.
Phase III seeks to further determine the effectiveness of the drug. This is done by testing the drug on
different populations, meaning that testing will be done on more people, testing will be done on
different drug doses, and the drug will be tested on patients who are also taking other drugs. If
Phases I through III show the investigational new drug to be safe and effective, then the
pharmaceutical company will file a New Drug Application (NDA). The NDA includes both the
results of the first three trial phases and data on how the drug is manufactured (Frank & Hargreaves,
2003; Lipsky & Sharp, 2001;

Optimization of Ritalin for more Effective Results Essay
Ritalin (Methylphenidate) Optimization
Ritalin Pills
Abstract:
Attention–deficit hyperactivity disorder (ADHD) is currently the dominating psychiatric disorder
found in children. The creation of the drug Ritalin based on the molecule
Methylphenidate in the early 90's sparked a widespread use of this psycho stimulant, which still
remains as one of the most popular drugs used to counteract the symptoms of ADHD. My ultimate
goal in this research project is to design analogs for the drug Ritalin in the hopes of discovering a
more effective version of this medication. Through research, it can be concluded that none the
analogs suggested are suitable candidates for new drugs based on the results.
Introduction:
With 3–5 percent of ... Show more content on Helpwriting.net ...
The molecular structure of methylphenidate contains a phenethylamine portion which superimposes
on its supposed neural substrates dopamine and norepinephrine, allowing it to interact with its
intended receptor (figure 2). (1) A closer examination of this compound's molecular structure reveals
that it complies with Lipinski's rule of five, even though its partition coefficient is yet to be found. It
molecular structure contains 3 hydrogen acceptors and 1 hydrogen donor, whiles its molecular
weight is 233.31 g/mol, well under the suggested limit of 500 g/mol.
In this project, analogs of the drug compound Ritalin (methylphenidate) will be designed in order to
attempt to optimize it. When the designs ar e complete, the software provided by the chemistry
department of UC Davis will be used to generate the necessary data to predict their effectiveness
and assess their potential in becoming suitable candidates for new drugs.
Fig. 2: Methylphenidate compared to
Dopamine and Amphetamine
The first analog of Ritalin (figure 3) has a structure that is somewhat similar to that of the original
drug. However, the ester functional group(figure 4) is replaced by an imine group (figure 5). This
creates a molecule that has one less hydrogen bond acceptor, making it less polar then the original
structure of Ritalin. The possible consequences of this change consist of both a

As mentioned in class, as well as in the Krishna (2008) article, the drug development and approval
process is an extensive and costly endeavor. The goal of experimental medicine is to increase the
efficiency of drug development by providing a better understanding of the drug's mechanism(s) of
action, dose response, efficacy, and safety, allowing the process to be accelerated for the most
promising and efficacious candidates (Krishna, Herman, & Wagner, 2008). Preclinical testing begins
with identifying the ideal drug target. The target should be disease–modifying and/or have a proven
function in the pathophysiology of the disease. Target expression should not be uniformly
distributed throughout the body. There should also be a favorable IP ... Show more content on
Helpwriting.net ...
The main goal in Phase I is to find out if the investigational new drug is safe. In this first phase of
human testing, testing determines the correct dosing and exposes the most common side effects. If
the investigational new drug is found to be safe, Phase II of human testing can begin. The main goal
of Phase II is to find out if the investigational new drug is effective. Unlike in Phase I, the patients
tested in Phase II are not healthy. In this phase, testing determines whether the drug works on
patients it was designed to help. Results are obtained by comparing the group of test patients to
other groups taking a different drug or taking a placebo. Phase III is the first large–scale trial of
human testing. This phase can only begin if the new drug shows to be effective in Phase II. Phase III
seeks to further determine the effectiveness of the drug. This is done by testing the drug on different
populations, meaning that testing will be done on more people, testing will be done with different
drug doses, and the drug will be tested on patients who are also taking other drugs. If Phases I
through III show the investigational new drug to be safe and effective, then the pharmaceutical
company will file a New Drug Application (NDA). The NDA includes both the results of the first
three trial phases and data on how the drug is manufactured (Frank & Hargreaves, 2003; Lipsky &
Sharp, 2001; Krishna,

Protein Synthesis Lab Report
PEGylation is the chemical reaction wherein poly (ethylene glycol) or (PEG) is covalently
conjugated to a protein. The resulting protein will attain improved pharmacokinetics when compared
to the native protein such as increased in vivo half–life, decrease immunogenicity, increased
hydrophilicity etc. The objective of this experiment is to PEGylate the protein lysozyme (lys) and
study the kinetics of the PEG–lys when treated with the protein digestive enzyme trypsin. Designing
generic therapeutic is currently on the forefront of Pharmaceutical biotechnology. One attractive
technique in this area is PEGylation. PEG is non–toxic and is FDA approved. Chronic Hepatitis C is
currently curable due to the availability of the PEG interferon–α2b (Alconel ... Show more content
on Helpwriting.net ...
This results in an imine bond between PEG and the protein. This imine bond is then reduced into an
amine bond using sodium cyanoborohydride. Sodium cyanoborohydride is a weak reducing agent
and therefore it is used in this PEGylation reaction so as to prevent complete reduction of the PEG
itself. In addition, this is a liquid phase reaction therefore there is no control on specificity of
PEGylation degree. This leads to the formation of mono– di– tri– PEGylated proteins. In this
experiment 5 kDa and 10 kDa PEGs were used coat the lysozyme and the reaction profile was
assessed using SDS–PAGE. Sodium Docecyl Sulphate (SDS) is a negatively charged detergent
which coats the amino acids with in the proteins. Therefore there will be a net negative charge on
the protein which defies its native charge. When placed within an electric field causes migration of
the protein towards the cathode. Protein passes through PAGE gel has pores which causes size based
separation. A molecular protein ladder is also run alongside the PEGylated reactions so as to conduct
semi–quanititative analysis on the conjugated lysozyme. Visualization of the PAGE gel using
coomassie brilliant blue (CBB) which only stains proteins. Since Iodine (I) is an electron acceptor it
complexes with PEG and PEG–I produces a reddish–brown color. Therefore, I is used to selectively
stain

Gelatin cryogel sheets (5%) were synthesized using...
Gelatin cryogel sheets (5%) were synthesized using glutaraldehyde as the cross–linker. The
aldehyde groups of glutaraldehyde form covalent imine bonds with amino groups of gelatin. Initially
different concentrations of gelatin were used (4%, 5%, 6% and 8% respectively). On physical
examination of the cryogels produced with these concentrations, it was observed that at higher
concentration of gelatin polymer (8%) the rate of polymerization was very fast and hence cryogel
sheets formed were not proper. As the percentage of gelatin was increased the amount of cross–
linker required was low i.e., the amount of cross–linker required decreases with increase in
monomer concentration. Increase in polymer concentration also leads to less elasticity ... Show more
content on Helpwriting.net ...
Decrease in glutaraldehyde cross–linker on increasing the polymer precursor might be happening
due to the increased probability of colliding polymers and cross linking agent in this unfrozen liquid
microphase where all chemical reactions take place. More probability of colliding might be
decreasing the amount of glutaraldehyde required to crosslink polymers for gel synthesis. It was also
observed that if the amount of glutaraldehyde used was more than the optimum concentrations
(Table 1.1), the gel formed lack porous network and were tough and brittle. When the
glutaraldehyde concentration was reduced and kept lower than the optimized one, the gels were
weak in mechanical strength. This observation suggests that there seems to be some competition
between the nucleation process which takes place in frozen regions and gelation process which takes
place in unfrozen liquid microphase. When the concentration of glutaraldehyde was lower than
optimum, nucleation process dominates the gelation process and the gels formed were weak due to
large pores and less polymer wall formation by cross linking of polymers. When glutaraldehyde
quantity was taken more than optimum, gelation dominates the nucleation process and the gels
formed were without any pores and were brittle. Figure 1.1A shows the digital images of optimized
gelatin sheets. Figure 1.1B and 1.1C shows that at an optimized polymer and cross–linker ratio

Numerical Modeling Of Turbulent Flow Through Bend Pipes Essay
NUMERICAL MODELING OF TURBULENT FLOW THROUGH BEND PIPES
Rana Roy Chowdhury1*, Md. Mahbubul Alam2
1Post Graduate Student, Department of Mechanical Engineering, CUET, Chittagong– 4349
2Professor, Department of Mechanical Engineering, CUET, Chittagong– 4349
*Corresponding Author: email: engr.rrc@gmail.com
Abstract– A numerical investigation has been carried out for incompressible turbulent flow through
900bend pipes. The model is based on the numerical solution of conservation equations of mass and
momentum. The results of the simulations of the flow in the form of contour and vector plots for
two types of pipe bend both mitre and smooth bend with seven different Reynolds numbers
(2.0+E04, 2.5+E04, 3.0+E04, 3.5+E04, 4.0+E04, 4.5+E04 and 5.0+ E04) are presented in this paper.
From the obtained results, it is seen that the mitre bend produces more turbulent kinetic energy, eddy
viscosity, skin friction factor compared to the smooth bend. To put an emphasis on the smooth bend
for different R/D ratios, the static pressure distribution along the inner, outer wall and the pressure
loss factor with different Re numbers are analyzed. However, it is noticed that as Re increases the
pressure gradient changes rapidly at the inner and the outer wall of the bend. Again, the total
pressure loss factor k increases as the R/D ratio decreases and due to higher velocity heads factor k
decreases as Re increases. The numerical results are found to be in a good agreement with
experimental

Synthesis Of Aniline Lab Report
The synthesis required that the starting materials contain an aniline and aldehyde in order to produce
an imine, which is a primary amine. Using p–chlorobenzaldehyde and p–bromoaniline along with
the addition of dichloromethane and, in some cases, a water trapping reagent, the group was able to
synthesize 4–bromo–N–[4–(chlorophenyl)methylene]–benzenamine. Three different reactions using
the same reactants but different water trapping agents were employed in order to determine which
trapping agent, either molecular sieves or sodium sulfate, would remove the most water and leave
the purest product. Upon completion of TLC, melting point analysis, as well as IR spectrum, and 1H
NMR analysis, it was determined that the reaction using the molecular sieves produced the purest
substance. Furthermore, it was hypothesized that the molecular sieves would produce the greatest
percent yield of pure product since it is the only water trapping agent that can also separate out non–
water ... Show more content on Helpwriting.net ...
The use of methanol to dissolve any lingering impurities following the drying phase helped
conclude that the molecular sieves produced the greatest amount of pure product followed by
sodium sulfate with the monitor reaction containing no water trapping reagent having the least
amount.
Introduction
The nucleophilic addition reaction of an aldehyde with an amine gave rise to an imine with the
addition of heat or an acid or base catalyst being used to speed up the product separation or removal
of water to complete the reaction. The amine acted as a nucleophile and attached itself to the
aldehyde, or carbonyl group. Imines, known as azomethines or Schiff bases, are compounds that are
represented by the general formula R3R2C=NR1.1 Schiff bases can be formed from aldehydes or
ketones but an amine is always required to complete the reaction. When it comes to biological roles,
imines are crucial intermediates for both enzymatic and pharmaceutical interest but

Hepataminophen Research Paper
As a widely used analgesic and antipyretic agent, acetaminophen (APAP) overdose induced
hepatotoxicity is one of the most common causes of acute liver failure in the USA and in most
Western European countries [1]. Although a number of studies have forced on the influences of N–
acetyl–p–benzoquinone imine (NAPQI), a highly reactive metabolite of APAP that depletes hepatic
glutathione, and increases in oxidative stress during APAP toxicity [2], other mechanisms such as
immune response also raise the susceptibility in the early stages of APAP–induced liver injury [3].
Accumulating evidence demonstrates a critical role of inflammatory cytokine released in early liver
damage after APAP intoxication [4, 5]. Kupffer cells (KCs), the liver resident macrophages, are
major sources of reactive oxygen species (ROS) and inflammatory ... Show more content on
Helpwriting.net ...
Thus, there is an urgency to evaluate the effects of immune response on APAP toxicity using a
human KCs and hepatocyte co–culture system. Since a 3D multicellular system containing
hepatocytes and other non–hepatocytes can better reflect the cell–cell interactions of a real situation
[11], in this study, we used the 3D liver microtissues consisting of primary human hepatocytes
(PHH) and KCs (1 : 1) to study the inflammation–mediated hepatotoxicity after acetaminophen
overdose.
Because large doses of LPS cause severe liver injury, whereas small doses of LPS results in the
absence of liver damage [6], there is a necessity to determine the optimal dosage of LPS. Therefore,
we first carried out a pilot dose–finding study to explore the dose of LPS that can stimulate the
production of cytokines without inducing massive cell death of PHH and KCs cells. Meanwhile, we
also tested a few doses of APAP–LPS co–exposures to get an impression on the abilities of these
combinations to induce the cytotoxicity and cytokine

Unsaturation Lab Report
If the degree of unsaturation = 2, there are a few possibilities i.e. (i) presence of one triple bond, (ii)
two rings, (iii) two double bonds or (iv) one ring and one double bond. If the degree of unsaturation
= 3, various combinations involving rings and / or double bonds are possible. If the degree of
unsaturation = 4, it could indicate the presence of a benzene ring. If the degree of unsaturation > 4, it
could indicate the presence of a benzene ring and a ring / double bond. (Consider also the
possibilities for lower degrees of unsaturation.) Example 6 Determine the degree of unsaturation for
the following compounds, based on their structures. (a) (b) ... Show more content on Helpwriting.net
...
No rotation unless bond is broken. Each carbon atom of the C=C bond has two different
substituents attached to it.  A cis–isomer has two higher Mr groups on the same side of the C=C
bond.  A trans–isomer has two higher Mr groups on the opposite sides of the C=C bond. 
Comment: Many students mistakenly think that the reason why there is no free rotation of the C=C
bond is because of the strong bond. If that is the case, then why is there free rotation of the C–C
bond when the  bond is even stronger than the  bond? The correct explanation should be: There
is no free rotation of the C=C bond because of the bond. For a bond to be formed, the p–
orbitals must be properly aligned. Free rotation about the C=C bond is equivalent to breaking the
bond and misaligning the p–orbitals.  Comment: Geometrical isomerism is NOT POSSIBLE if
one of the carbon atoms in the C=C bond is bonded to two identical substituents. Less common
examples: a) C=N bond in imine b) N=N

Alkylation of Azole Derivatives Essay
Table of Contents
Introduction...................................................................................
Background....................................................................................
Previous Work..............................................................................
Results and Discussion.....................................................................
Future Work......................................................................................
Experimental Procedures........................................................................
References..........................................................................................
Introduction Synthesis of molecules is very important in the development of natural products used in
medicine today.1 However, there are many problems with the current synthesis method that conflict
with many of the guidelines in the 12 Principles of Green Chemistry and are potentially hazardous.2
The proposed research plan includes the formation of a salt by allylation followed by the Aza–
Claisen rearrangement which ... Show more content on Helpwriting.net ...
To achieve this goal, Green Chemistry focuses specifically on preventing waste, designing safer
chemicals and synthetic methods, and saving energy and money.4 This research of azole synthesis is
a study incorporating these practices of green chemistry, consequently improving the current
synthesis method for pharmaceutical production. The benefits of Green Chemistry are countless.
From an economic point of view, businesses can save large amounts of money by eliminating the
costly efforts of excessive pollutant prevention. Also, increasing efficiency of materials used and
improving the yields of reactions is minimizing the cost of materials for production. Using organic
solvents along with reducing pollution creates a safer environment for workers and enhances public
safety. 4 Therefore, these improvements are very important and should be included in the current
synthetic methods used in industries today. Forming C–C bonds at the C2 of azoles is a necessary
step in the beginning of the current azole synthesis method which generally requires using strong
bases, low temperatures, and/or expensive, toxic precious metal catalysts.5,6,7 By substituting these
issues with organic solvents, ambient temperature, and weaker bases, a synthesis method better
suited for pharmaceutical industries is created.
Background Even though previous methods of azole synthesis have

Acute Liver Failure Case Studies
Looking at Jonathon's labs, vital signs, and physical assessment, along with his recent admissions, I
would diagnose him with acetaminophen induced hepatotoxicity. Patients with acute liver failure
can present with symptoms such as fever, abdominal pain, fatigue, and anorexia (Lancaster, Hiatt, &
Zarrinpar, 2015). Jonathon is presenting with fever and abdominal pain. His LFT indicate that acute
liver failure is present. At his previous visit, I prescribed him to take the maximum dose of
acetaminophen at 4g/day. Since Johnathon admits to taking several over the counter (OTC) brand
medications it is possible he took Tylenol, which is the brand name for acetaminophen, and not
realizing that he was overdosing. Acetaminophen can be found in many OTC medications. I would
ask Johnathon for a complete list of all the OTC medications he was taking, or for him to remember
as many as he could. His drinking is also a major concern. Large alcoholic beverage consumption in
combination with high doses of acetaminophen can greatly affect the liver. At this point I would be
extremely concerned for Jonathon's health. ... Show more content on Helpwriting.net ...
The majority of acetaminophen, approximately 90%, will be metabolized by glucuronidation
(Lancaster et al., 2015). Approximately 10% will be metabolized by cytochrome p450 (Lancaster et
al., 2015). From there it will become the reactive metabolite N–acetyl–p–benzo–quinone imine
(NAPQI) (Lancaster et al., 2015). Under normal circumstances, glutathione (GSH) will convert
NAPQI to a nontoxic metabolite (Lancaster et al., 2015). In cases where GSH depletion is present
due to acetaminophen overdose, malnutrition, or alcoholism, NAPQI cannot be converted, leading
to increased NAPQI levels and subsequently liver damage (Lancaster et al.,

Lab Report Of Vanillin
CHAPTER 1
INTRODUCTION
1.1 Background and Problem Statement
1.1.1 Schiff Base
The condensation product of primary amines with active carbonyl compounds have resulted in the
formation of Schiff base compound. This has been reported by Hugo Schiff in 1864. Schiff base
compound contain azomethine –C≡N with a general formula RHC=N–R' where R and R' are alkyl,
aryl, cyclo alkyl or heterocyclic groups which may be variously substituted. These compounds are
also known as anils, imines or azomethines (Mishra N. et al, 2013). Structurally, a Schiff base is a
nitrogen analogue of an aldehyde or ketone in which the carbonyl group (C=O) has been replaced by
an imine or azomethine group (Figure 1.1) (Abu–Dief M.A et al, 2015).
Figure 1.1 General ... Show more content on Helpwriting.net ...
The development of new antibacterial agents with novel and more efficient mechanisms of action is
definitely an urgent medical need. Schiff bases have been pointed to as promising antibacterial
agents (Brodowska K. et al, 2014). With respect to the biological activity and desirable
physicochemical, stereochemical, electrochemical, structural and catalytic properties of Schiff base
metal complexes, their values has attracted significant attention and is also relevant for their
application as tools for the analysis of pharmacological constituents (Ejidike P.I et al, 2015).
Chigurupati S. (2015) reported that considering the increased incidences of severe opportunistic
bacterial infections in immunological deficient patients together with the development of resistance
among pathogenic gram positive and gram negative bacteria, there is a great need in finding new
compounds that may be effective against antibiotic resistant bacteria.
1.2 Problem

Quaternary Ammonium Compounds Research Paper
Quaternary ammonium compounds (QACs), also known as quats, are usually positively charged
molecules with a nitrogen atom that has four other bonds (Sabapathy, 1994). Because of the positive
charge on the nitrogen atom, quaternary ammonium compounds are formulated as a salt and are
usually paired with a negatively charged compound or ion (Sabapathy, 1994). In terms of practical
use, QACs are commonly used as a broad spectrum antimicrobial. In other words, it affects the two
major types of bacteria, Gram–positive bacteria and Gram–negative (Lu, Wu, & Fu, 2007). QACs
can be found in a variety of products, ranging from household products such as Lysol disinfecting
wipes to sanitizing agents commonly used in food service. As with any chemical, toxicity is based
on dosage . It is known that QACs can be toxic, if not ... Show more content on Helpwriting.net ...
For quaternary ammonium compounds, despite the structural motif of the positively charged
nitrogen atom, it can be classified within different categories based off the specific compound.
However, it appears that affecting cell membrane is the more common mechanism. The chemicals,
diquat and paraquat, which are actually used as an herbicide, are examples of quaternary ammonium
compounds that do not really fall within one specific category of mechanism. Through a redox
reaction, both of these chemicals form superoxide (O2–) Superoxide is a free radical, which
typically is a type of molecule with an unpaired electron and is consequently extremely reactive.
Therefore, superoxide proceeds to remove electrons from other compounds within the vicinity,
which could be as vital as DNA. Thus, the mode of action for diquat and paraquat is not specific to
bacteria or unwanted plant species, but rather it is similar in plants, bacteria, and

Paracetamol Synthesis and Uses Essay
Paracetamol – Synthesis and Uses Discovered in 1877 by Harmon Northrop Morse at the John
Hopkins University, Paracetamol was one of several aniline deriviatives that was found to have
analgesic and antipyretic properties (Brodie 23). It was first synthesized by the reduction of p–
nitrophenol with tin in glacial acetic acid; however was not used classified as a medication until ten
year later (Bertolini 264). Initially, phenacetin, a closely related compound that exhibited similar
physiological effects, became the popular over the counter drug for headaches (Bertolini 251).
However, later research by Brodie and Axelrod in 1949 found that phenacetin was in fact
metabolized into paracetamol within the body (Brodie and Axelrod 60). ... Show more content on
Helpwriting.net ...
This is an electrophilic aromatic substitution reaction where a hydrogen on the aromatic ring is
replaced with a nitro group. The hydroxyl group on the aromatic ring is an electron–donating group
and therefore serves as an ortho–para director. Through the nitration reaction, two products are
formed: o–nitrophenol and p–nitrophenol. In comparing the stability of the two resulting products,
o–nitrophenol is less stable due to steric hinderance and proximity of the hydroxyl and nitro group
to one another. On the other hand, p–nitrophenol does not experience the same steric hinderance
since the two group as on opposite sides of the aromatic ring and therefore do not interfere with one
another. As a result, p–nitrophenol is the major product of reaction. It is also the product of interest
and will be involved in the next step of the synthesis.
Subsequently, p–nitrophenol is reduced by sodium borohydride to give 4–aminophenol. In an
industrial synthesis, hydrogenation is used for reduction instead of sodium borohydride to produce
an identical product(Travis 764). The use of hydrogenation is more efficient when produce larger
quantities. In the last step of the synthesis, 4–aminophenol is acylated in a reaction with acetic
anhydride. In this reaction, the electron pair on nitrogen of the amine group attack the one of the
carbonyls on the acid anhydride. The electrons move up to the oxygen, forming a negative anion,
and a bond is formed

Acetaminophen

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