Dinuclear cyano-bridged Co-III-Fe-II complexes as precursors for molecular mixed-valence complexes of higher nuclearity

The preparation and characterization of a series of trinuclear mixed-valence cyano-bridged Co-III-Fe-II-Co-III compounds derived from known dinuclear [{LnCoIII(mu-NC)}Fe-II(CN)(5)](-) complexes (L-n = N-5 or N3S2 n-membered pendant amine macrocycle) are presented. All of the new trinuclear complexes were fully characterized spectroscopically (UV-vis, IR, and C-13 NMR). Complexes exhibiting a trans and cis arrangement of the Co-Fe-Co units around the [Fe(CN)(6)](4-) center are described (i.e., cis/trans-[{LnCoIII(mu-NC)}(2)Fe-II(CN)(4)](2+)), and some of their structures are determined by X-ray crystallography. Electrochemical experiments revealed an expected anodic shift of the Fe-III/II redox potential upon addition of a tripositively charged {(CoLn)-L-III} moiety. The Co-III/II redox potentials do not change greatly from the di- to the trinuclear complex, but rather behave in a fully independent and noncooperative way. In this respect, the energies and extinction coefficients of the MMCT bands agree with the formal existence of two mixed-valence Fe-II-CN-Co-III units per molecule. Solvatochromic experiments also indicated that the MMCT band of these compounds behaves as expected for a class II mixed-valence complex. Nevertheless, its extinction coefficient is dramatically increased upon increasing the solvent donor number.

Valence-tautomeric RbMnFe Prussian blue analogues:composition and time stability investigation

Three different stoichiometric forms of RbMn[Fe(CN) ]y·zHO [x = 0.96, y = 0.98, z = 0.75 (1); x = 0.94, y = 0.88, z = 2.17 (2); x = 0.61, y = 0.86, z = 2.71 (3)] Prussian blue analogues were synthesized and investigated by magnetic, calorimetric, Raman spectroscopic, X-ray diffraction, and Fe Mössbauer spectroscopic methods. Compounds 1 and 2 show a hysteresis loop between the high-temperature (HT) Fe(S = 1/2)-CN-Mn(S = 5/2) and the low-temperature (LT) Fe(S = 0)-CN-Mn(S = 2) forms of 61 and 135 K width centered at 273 and 215 K, respectively, whereas the third compound remains in the HT phase down to 5 K. The splitting of the quadrupolar doublets in the Fe Mössbauer spectra reveal the electron-transfer-active centers. Refinement of the X-ray powder diffraction profiles shows that electron-transfer-active materials have the majority of the Rb ions on only one of the two possible interstitial sites, whereas nonelectron-transfer-active materials have the Rb ions equally distributed. Moreover, the stability of the compounds with time and following heat treatment is also discussed. © Wiley-VCH Verlag GmbH & Co. KGaA, 2009.

Theoretical study of chloroperoxidase catalyzed chlorination of beta-cyclopentanedione and role of water in the chlorination mechanism

Chloroperoxidase (CPO) is a potential biocatalyst for use in asymmetric synthesis. The mechanisms of CPO catalysis are therefore of interest. The halogenation reaction, one of several chemical reactions that CPO catalyzes, is not fully understood and is the subject of this dissertation. The mechanism by which CPO catalyzes halogenation is disputed. It has been postulated that halogenation of substrates occurs at the active site. Alternatively, it has been proposed that hypochlorous acid, produced at the active site via oxidation of chloride, is released prior to reaction, so that halogenation occurs in solution. The free-solution mechanism is supported by the observation that halogenation of most substrates often occurs non-stereospecifically. On the other hand, the enzyme-bound mechanism is supported by the observation that some large substrates undergo halogenation stereospecifically. The major purpose of this research is to compare chlorination of the substrate β-cyclopentanedione in the two environments. One study was of the reaction with limited hydration because such a level of hydration is typical of the active site. For this work, a purely quantum mechanical approach was used. To model the aqueous environment, the limited hydration environment approach is not appropriate. Instead, reaction precursor conformations were obtained from a solvated molecular dynamics simulation, and reaction of potentially reactive molecular encounters was modeled with a hybrid quantum mechanical/molecular mechanical approach. Extensive work developing parameters for small molecules was pre-requisite for the molecular dynamics simulation. It is observed that a limited and optimized (active-site-like) hydration environment leads to a lower energetic barrier than the fully solvated model representative of the aqueous environment at room temperature, suggesting that the stable water network near the active site is likely to facilitate the chlorination mechanism. The influence of the solvent environment on the reaction barrier is critical. It is observed that stabilization of the catalytic water by other solvent molecules lowers the barrier for keto-enol tautomerization. Placement of water molecules is more important than the number of water molecules in such studies. The fully-solvated model demonstrates that reaction proceeds when the instantaneous dynamical water environment is close to optimal for stabilizing the transition state.

Low valence cation doping of bulk Cr2O3: Charge compensation and oxygen vacancy formation

The different oxidation states of chromium allow its bulk oxide form to be reducible, facilitating the oxygen vacancy formation process, which is a key property in applications such as catalysis. Similar to other useful oxides such as TiO2, and CeO2, the effect of substitutional metal dopants in bulk Cr2O3 and its effect on the electronic structure and oxygen vacancy formation are of interest, particularly in enhancing the latter. In this paper, density functional theory (DFT) calculations with a Hubbard + U correction (DFT+U) applied to the Cr 3d and O 2p states, are carried out on pure and metal-doped bulk Cr2O3 to examine the effect of doping on the electronic and geometric structure. The role of dopants in enhancing the reducibility of Cr2O3 is examined to promote oxygen vacancy formation. The dopants are Mg, Cu, Ni, and Zn, which have a formal +2 oxidation state in their bulk oxides. Given this difference in host and, dopant oxidation states, we show that to predict the correct ground state two metal dopants charge compensated with an oxygen vacancy are required. The second oxygen atom removed is termed "the active" oxygen vacancy and it is the energy required to remove this atom that is related to the reduction process. In all cases, we find that substitutional doping improves the oxygen vacancy formation of bulk Cr2O3 by lowering the energy cost.

A Theoretical and Synthetic Investigation of New Donors for Organic Electro-Optic Chromophores: Understanding the Effects of Structure and Substituents on Donor Strength

Thesis (Ph.D.)--University of Washington, 2016-08

Identification of protein targets of nevirapine reactive metabolites using click chemistry and mass spectrometry-based differential proteomics

Abstract : Adverse drug reactions (ADRs) are undesirable effects caused after administration of a single dose or prolonged administration of drug or result from the combination of two or more drugs. Idiosyncratic drug reaction (IDR) is an adverse reaction that does not occur in most patients treated with a drug and does not involve the therapeutic effect of the drug. IDRs are unpredictable and often life-threatening. Idiosyncratic reaction is dependent on drug chemical characteristics or individual immunological response. IDRs are a major problem for drug development because they are usually not detected during clinical trials. In this study we focused on IDRs of Nevirapine (NVP), which is a non-nucleoside reverse transcriptase inhibitor used for the treatment of Human Immunodeficiency Virus (HIV) infections. The use of NVP is limited by a relatively high incidence of skin rash. NVP also causes a rash in female Brown Norway (BN) rats, which we use as animal model for this study. Our hypothesis is that idiosyncratic skin reactions associated with NVP treatment are due to post-translational modifications of proteins (e.g., glutathionylation) detectable by MS. The main objective of this study was to identify the proteins that are targeted by a reactive metabolite of Nevirapine in the skin. The specific objectives derived from the general objective were as follow: 1) To implement the click chemistry approach to detect proteins modified by a reactive NVP-Alkyne (NVP-ALK) metabolite. The purpose of using NVP-ALK was to couple it with Biotin using cycloaddition Click Chemistry reaction. 2) To detect protein modification using Western blotting and Mass Spectrometry techniques, which is important to understand the mechanism of NVP induced toxicity. 3) To identify the proteins using MASCOT search engine for protein identification, by comparing obtained spectrum from Mass Spectrometry with theoretical spectrum to find a matching peptide sequence. 4) To test if the drug or drug metabolites can cause harmful effects, as the induction of oxidative stress in cells (via protein glutathionylation). Oxidative stress causes cell damage that mediates signals, which likely induces the immune response. The results showed that Nevirapine is metabolized to a reactive metabolite, which causes protein modification. The extracted protein from the treated BN rats matched 10% of keratin, which implies that keratin was the protein targeted by the NVP-ALK.

A THEORETICAL STUDY OF INTERACTION OF NANOPARTICLES WITH BIOMOLECULE

Many types of materials at nanoscale are currently being used in everyday life. The production and use of such products based on engineered nanomaterials have raised concerns of the possible risks and hazards associated with these nanomaterials. In order to evaluate and gain a better understanding of their effects on living organisms, we have performed first-principles quantum mechanical calculations and molecular dynamics simulations. Specifically, we will investigate the interaction of nanomaterials including semiconducting quantum dots and metallic nanoparticles with various biological molecules, such as dopamine, DNA nucleobases and lipid membranes. Firstly, interactions of semiconducting CdSe/CdS quantum dots (QDs) with the dopamine and the DNA nucleobase molecules are investigated using similar quantum mechanical approach to the one used for the metallic nanoparticles. A variety of interaction sites are explored. Our results show that small-sized Cd4Se4 and Cd4S4 QDs interact strongly with the DNA nucleobase if a DNA nucleobase has the amide or hydroxyl chemical group. These results indicate that these QDs are suitable for detecting subcellular structures, as also reported by experiments. The next two chapters describe a preparation required for the simulation of nanoparticles interacting with membranes leading to accurate structure models for the membranes. We develop a method for the molecular crystalline structure prediction of 1,2-Dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC), 1,2-Dimyristoyl-sn-glycero-3-phosphorylethanolamine (DMPE) and cyclic di-amino acid peptide using first-principles methods. Since an accurate determination of the structure of an organic crystal is usually an extremely difficult task due to availability of the large number of its conformers, we propose a new computational scheme by applying knowledge of symmetry, structural chemistry and chemical bonding to reduce the sampling size of the conformation space. The interaction of metal nanoparticles with cell membranes is finally carried out by molecular dynamics simulations, and the results are reported in the last chapter. A new force field is developed which accurately describes the interaction forces between the clusters representing small-sized metal nanoparticles and the lipid bilayer molecules. The permeation of nanoparticles into the cell membrane is analyzed together with the RMSD values of the membrane modeled by a lipid bilayer. The simulation results suggest that the AgNPs could cause the same amount of deformation as the AuNPs for the dysfunction of the membrane.

[theoretical Construction In The Sociology Of Health: A Reflection On Its Trajectory].

The scope of this paper is to reflect on the theoretical construction in the constitution of the sociology of health, still called medical sociology in some countries. Two main ideas constitute the basis for this: interdisciplinarity and the degree of articulation in the fields of medicine and sociology. We sought to establish a dialogue with some dimensions - macro/micro, structure/action - that constitute the basis for understanding medicine/health in relation to the social/sociological dimension. The main aspects of these dimensions are initially presented. Straus' two medical sociologies and the theory/application impasses are then addressed, as well as the dilemmas of the sociology of medicine in the 1960s and 1970s. From these analyses the theoretical production before 1970 is placed as a counterpoint. Lastly, the sociology of health is seen in the general context of sociology, which underwent a fragmentation process from 1970 with effects in all subfields of the social sciences. This process involves a rethinking of the theoretical issues in a broadened spectrum of possibilities. The 1980s are highlighted when theoretical issues in the sociology of health are reinvigorated and the issue of interdisciplinarity is once again addressed.

The Crystal-t Algorithm: A New Approach To Calculate The Sle Of Lipidic Mixtures Presenting Solid Solutions.

Lipidic mixtures present a particular phase change profile highly affected by their unique crystalline structure. However, classical solid-liquid equilibrium (SLE) thermodynamic modeling approaches, which assume the solid phase to be a pure component, sometimes fail in the correct description of the phase behavior. In addition, their inability increases with the complexity of the system. To overcome some of these problems, this study describes a new procedure to depict the SLE of fatty binary mixtures presenting solid solutions, namely the Crystal-T algorithm. Considering the non-ideality of both liquid and solid phases, this algorithm is aimed at the determination of the temperature in which the first and last crystal of the mixture melts. The evaluation is focused on experimental data measured and reported in this work for systems composed of triacylglycerols and fatty alcohols. The liquidus and solidus lines of the SLE phase diagrams were described by using excess Gibbs energy based equations, and the group contribution UNIFAC model for the calculation of the activity coefficients of both liquid and solid phases. Very low deviations of theoretical and experimental data evidenced the strength of the algorithm, contributing to the enlargement of the scope of the SLE modeling.

Hypobromous Acid, A Powerful Endogenous Electrophile: Experimental And Theoretical Studies.

Hypobromous acid (HOBr) is an inorganic acid produced by the oxidation of the bromide anion (Br(-)). The blood plasma level of Br(-) is more than 1,000-fold lower than that of chloride anion (Cl(-)). Consequently, the endogenous production of HOBr is also lower compared to hypochlorous acid (HOCl). Nevertheless, there is much evidence of the deleterious effects of HOBr. From these data, we hypothesized that the reactivity of HOBr could be better associated with its electrophilic strength. Our hypothesis was confirmed, since HOBr was significantly more reactive than HOCl when the oxidability of the studied compounds was not relevant. For instance: anisole (HOBr, k2=2.3×10(2)M(-1)s(-1), HOCl non-reactive); dansylglycine (HOBr, k2=7.3×10(6)M(-1)s(-1), HOCl, 5.2×10(2)M(-1)s(-1)); salicylic acid (HOBr, k2=4.0×10(4)M(-1)s(-1), non-reactive); 3-hydroxybenzoic acid (HOBr, k2=5.9×10(4)M(-1)s(-1), HOCl, k2=1.1×10(1)M(-1)s(-1)); uridine (HOBr, k2=1.3×10(3)M(-1)s(-1), HOCl non-reactive). The compounds 4-bromoanisole and 5-bromouridine were identified as the products of the reactions between HOBr and anisole or uridine, respectively, i.e. typical products of electrophilic substitutions. Together, these results show that, rather than an oxidant, HOBr is a powerful electrophilic reactant. This chemical property was theoretically confirmed by measuring the positive Mulliken and ChelpG charges upon bromine and chlorine. In conclusion, the high electrophilicity of HOBr could be behind its well-established deleterious effects. We propose that HOBr is the most powerful endogenous electrophile.

Comparison of some theoretical models for fittings of the temperature dependence of the fundamental energy gap in GaAs

In this work we report on a comparison of some theoretical models usually used to fit the dependence on temperature of the fundamental energy gap of semiconductor materials. We used in our investigations the theoretical models of Viña, Pässler-p and Pässler-ρ to fit several sets of experimental data, available in the literature for the energy gap of GaAs in the temperature range from 12 to 974 K. Performing several fittings for different values of the upper limit of the analyzed temperature range (Tmax), we were able to follow in a systematic way the evolution of the fitting parameters up to the limit of high temperatures and make a comparison between the zero-point values obtained from the different models by extrapolating the linear dependence of the gaps at high T to T = 0 K and that determined by the dependence of the gap on isotope mass. Using experimental data measured by absorption spectroscopy, we observed the non-linear behavior of Eg(T) of GaAs for T > ΘD.

Escrita científica de alunos de graduação em química: análise de relatórios de laboratório

The purpose of this study was to analyze written arguments found within laboratory reports by undergraduate students in a practical inorganic chemistry course. The quality of students' argumentation was analyzed based on the argumentation model developed by Kelly and Takao. Students presented scientific arguments grounded in data and building toward theoretical assertions. This indicates that students have some understanding of the rhetorical power of data in their explanations. The findings of this study also support the idea that Kelly and Takao's model is effective in other disciplines and in other rhetorical tasks distinct from those originally analyzed by them in their domain of oceanography.

A theoretical study of the tautomerism and vibrational spectra of 4,5-diamine-2,6-dimercaptopyrimidine

The 4,5-diamine-2,6-dimercaptopyrimidine (DADMcP) compound is an interesting multifunctional species exhibiting a rather complex tautomerism, encompassing nine tautomeric forms. Investigation of tautomerism in this compound has been carried out by means of FTIR spectroscopy, in association with ab-initio HF/SCF and DFT calculations. According to this study three tautomers are energetically favored; the thione form being the most stable one. The theoretical vibrational spectra of such tautomeric forms have been successfully simulated by means of DFT calculations, allowing the elucidation and assignment of the complex composition of the vibrational bands observed for the mixture of isomers.