Conformational behavior of different possible ways of oligoglycine formation in a solvent-free environment

The possible ways for glycine oligopeptide formation in gas phase, both in the extended P-strand like conformation and folded 2(7)-ribbon like conformations are analyzed using quantum chemical calculations. We focus on the sequential formation of peptide bond through upgradation of the immediate lower order molecule and observe the consequences in other related processes like oligoglycine formation through simultaneous peptide linkage of n glycine monomers and interchange of molecular conformation through peptide linkage. A comparison is made between the structures and binding energies obtained for both conformers. All binding energies are increased by the zero-point energy contribution. The role of electron correlation effects is briefly analyzed. The folded 2(7)-ribbon-like conformations in vacuo are found to be more stable in comparison to the extended structure. (c) 2007 Elsevier B.V. All rights reserved.

Stability and interface properties of thin cellulose ester films adsorbed from acetone and ethyl acetate solutions

Stability and interface properties of cellulose acetate propionate (CAP) and cellulose acetate butyrate (CAB) films adsorbed from acetone or ethyl acetate onto Si wafers have been investigated by means of contact angle measurements and atomic force microscopy (AFM). Surface energy (gamma(total)(S)) values determined for CAP adsorbed from acetone are larger than those from ethyl acetate. In the case of CAB films adsorbed from ethyl acetate and acetone were similar. Dewetting was observed by AFM only for CAP films prepared from ethyl acetate. Positive values of effective Hamaker constant (A(eff)) were found only for CAP prepared from ethyl acetate, corroborating with dewetting phenomena observed by AFM. Oil the contrary, negative values of A(eff) were determined for CAP and CAB prepared from acetone and for CAB prepared from ethyl acetate, Corroborating with experimental observations. Sum frequency generation (SFG) vibrational spectra indicated that CAP and CAB films prepared from ethyl acetate present more alkyl groups oriented perpendicularly to the polymer-air interface than those films prepared from acetone. Such preferential orientation corroborates with macroscopic contact angle measurements. Moreover, SFG spectra showed that acetone hinds strongly to Si wafers, creating a new surface for CAP and CAB films. (C) 2008 Elsevier Inc. All rights reserved.

Thermodynamic characterization of the palm tree Roystonea regia peroxidase stability

The structural stability of a peroxidase, a dimeric protein from royal palm tree (Roystonea regia) leaves, has been characterized by high-sensitivity differential scanning calorimetry, circular dichroism, steady-state tryptophan fluorescence and analytical ultracentifugation under different solvent conditions. It is shown that the thermal and chemical (using guanidine hydrochloride (Gdn-HCl)) folding/unfolding of royal palm tree peroxidase (RPTP) at pH 7 is a reversible process involving a highly cooperative transition between the folded dimer and unfolded monomers, with a free stabilization energy of about 23 kcal per mol of monomer at 25 degrees C. The structural stability of RPTP is pH-dependent. At pH 3, where ion pairs have disappeared due to protonation, the thermally induced denaturation of RPTP is irreversible and strongly dependent upon the scan rate, suggesting that this process is under kinetic control. Moreover, thermally induced transitions at this pH value are dependent on the protein concentration, allowing it to be concluded that in solution RPTP behaves as dimer, which undergoes thermal denaturation coupled with dissociation. Analysis of the kinetic parameters of RPTP denaturation at pH 3 was accomplished on the basis of the simple kinetic scheme N ->(k) D, where k is a first-order kinetic constant that changes with temperature, as given by the Arrhenius equation; N is the native state, and D is the denatured state, and thermodynamic information was obtained by extrapolation of the kinetic transition parameters to an infinite heating rate. Obtained in this way, the value of RPTP stability at 25 degrees C is ca. 8 kcal per mole of monomer lower than at pH 7. In all probability, this quantity reflects the contribution of ion pair interactions to the structural stability of RPTP. From a comparison of the stability of RPTP with other plant peroxidases it is proposed that one of the main factors responsible for the unusually high stability of RPTP which enhances its potential use for biotechnological purposes, is its dimerization. (c) 2008 Elsevier Masson SAS. All rights reserved.

Ab Initio Analysis of Monomers and Dimers of Trialkylphosphine Oxides: Structural and Thermodynamic Stability

Structural and thermodynamic stabilities of monomers and dimers of trialkylphosphine oxides (TRPO) were Studied using quantum chemistry calculations. Density functional theory calculations were carried Out and the structures Of four TRPO have been determined: TMPO (methyl; R = CH(3)), TEPO (ethyl; R = CH(3)CH(2)), TBPO (n-butyl; R = CH(3)(CH(2))(3)), and TOPO (n-octyl; R = CH(3)(CH(2))(7)). TRPO homodimers were investigated considering two isomeric possibilities for each dimer. Relative binding energies and the enthalpic and entropic contributions to the Gibbs free energy were Calculated for all dimers. The formation of dimers from the individual monomeric TRPO species as a function of temperature was also analyzed. (C) 2008 Wiley Periodicals, Inc. Int J Quantum Chem 109: 250-258, 2009

Existence and stability of new nanoreactors: Highly swollen hexagonal liquid crystals

We report the preparation of direct hexagonal liquid crystals, constituted of oil-swollen cylinders arranged on a triangular lattice in water. The volume ratio of oil over water, rho, can be as large as 3.8. From the lattice parameter measured by small-angle X-ray scattering, we show that all the oil is indeed incorporated into the cylinders, thus allowing the diameter of the cylinders to be controlled over one decade range, provided that the ionic strength of the aqueous medium and rho are varied concomitantly. These hexagonal swollen liquid crystals (SLCs) have been first reported with sodium dodecyl sulfate as anionic surfactant, cyclohexane as solvent, 1-pentanol as co-surfactant, and sodium chloride as salt (Ramos, L.; Fabre, P. Langmuir 1997, 13, 13). The stability of these liquid crystals is investigated when the pH of the aqueous medium or the chemical nature of the components (salt and surfactant) is changed. We demonstrate that the range of stability is quite extended, rendering swollen hexagonal phases potentially useful for the fabrication of nanomaterials. As illustrations, we finally show that gelation of inorganic particles in the continuous aqueous medium of a SLC and polymerization within the oil-swollen cylinders of a SLC can be conducted without disrupting the hexagonal order of the system.

Stability-indicating thin-layer chromatographic method for determination of darunavir in complex darunavir-beta-cyclodextrin in the presence of its degradation products

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Development and validation of a simple, rapid and stability-indicating high performance liquid chromatography method for quantification of norfloxacin in a pharmaceutical product

A stability-indication high performance liquid chromatographic method has been developed for the determination of norfloxacin in tablet dosage forms. Optimum separation was achieved in less than 7 minutes using Eclipse Plus Zorbax C18 Agilent, 150 mm×4.6 mm i.d., 5 μm particle size column. The analyte was resolved by using a mobile phase 5% acetic acid aqueous solution and methanol (80:20, v/v) at a flow rate 1.0 ml/min on an isocratic high performance liquid chromatographic system at a wavelength of 277 nm. Linearity, system suitability, precision, sensitivity, selectivity, specific, and robustness were established by International Conference Harmonization guidelines. For stress studies the drug was subjected to photolysis, oxidation, acid, alkaline and neutral conditions. The analytical conditions and the solvent developed provided good resolution within a short analysis time and economic advantages. The proposed method not required sophisticated and expensive instrumentation.

Development and validation of an economic, environmental friendly and stability-indicating analytical method for determination of ampicillin sodium for injection by RP-HPLC

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Development of an innovative, ecological and stability-indicating analytical method for semiquantitative analysis of ampicillin sodium for injection by thin layer chromatography (TLC)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Solvent-Resistant Polymeric Sensors for Adulteration Detection in Liquid Fuels

Polymeric sensors with improved resistance to organic solvents were produced via the layer-by-layer thin film deposition followed by chemical cross-linking. According to UV-vis spectroscopy, the mass loss of polyaniline/poly(vinyl alcohol) and polyaniline/novolac-type resin based films deposited onto glass slides was less than 20% when they were submitted to successive immersions (up to 3,000 immersion cycles) into commercially available ethanol and gasoline fuel samples. Polyallylamine hydrochloride/nickel tetrasulfonated phthalocyanine films presented similar stability. The electrical responses assessed by impedance spectroscopy of films deposited onto Au-interdigitated microelectrodes were relatively unaffected after continuous or cyclic immersions into both fuels. After these studies, an array including these polymeric sensors was employed to detect adulteration in ethanol and gasoline samples. After principal component analysis, it was possible to conclude that the proposed sensor array is capable to discriminate with remarkable reproducibility ethanol samples containing different amounts of water or else gasoline samples containing different amounts of ethanol. In both examples, more than 90% of data variance was retained in the first principal component. For each type of sample, ethanol and gasoline, it was found a linear correlation between one of the principal components and the sample's composition. These findings allow one to conclude that these films present great potential for the development of reliable and low-cost sensors for fuel analysis in liquid phase.

Scale Up of PLA Nanoparticle Synthesis by Solvent Displacement and Functionalization of the Particles with a Silica Shell for Targeted Drug Delivery Applications

Biodegradable polymer nanoparticles have the properties necessary to address many of the issues associated with current drug delivery techniques including targeted and controlled delivery. A novel drug delivery vehicle is proposed consisting of a poly(lactic acid) nanoparticle core, with a functionalized, mesoporous silica shell. In this study, the production of PLA nanoparticles is investigated using solvent displacement in both a batch and continuous manner, and the effects of various system parameters are examined. Using Pluronic F-127 as the stabilization agent throughout the study, PLA nanoparticles are produced through solvent displacement with diameters ranging from 200 to 250 nm using two different methods: dropwise addition and in an impinging jet mixer. The impinging jet mixer allows for easy scale-up of particle production. The concentration of surfactant and volume of quench solution is found to have minimal impact on particle diameter; however, the concentration of PLA is found to significantly impact the diameter mean and polydispersity. In addition, the stability of the PLA nanoparticles is observed to increase as residual THF is evaporated. Lastly, the isolated PLA nanoparticles are coated with a silica shell using the Stöber Process. It is found that functionalizing the silica with a phosphonic silane in the presence of excess Pluronic F-127 decreases coalescence of the particles during the coating process. Future work should be conducted to fine-tune the PLA nanoparticle synthesis process by understanding the effect of other system parameters and in synthesizing mesoporous silica shells.

Synthesis, structure, and stability of metal-organic frameworks

Metal-organic frameworks (MOFs) obtained much attention because of their unusual structures and properties as well as their potential applications. This dissertation research was focused on (1) the effects of synthesis conditions on the structures of MOFs, (2) the thermal stability of MOFs, (3) pressure-induced amorphization, and (4) the effect of high-valent ions on the structure of a MOF. This research demonstrated that the crystal structure of MOF-5 could be controlled by drying solvents. If the vacuum solvent is dimethylformamide (DMF), the crystal structure of MOF-5 is tetragonal. In contrast, if the DMF is displaced by CH2Cl2 before the vacuum, the obtained MOF-5 occupies a cubic structure. Furthermore, it was found that the tetragonal MOF-5 exhibited a mediate surface area (300-1000 m2/g). The surface area of tetragonal MOF-5 is also dependent on Zn(NO3)2/H2BDC (H2BDC: terephthalic acid) molar ratios used for its synthesis. The optimum ratio is 1.38, at which synthesized tetragonal MOF-5 exhibits the highest crystallinity and surface area (1297 m2/g). The thermal stability and decomposition of MOF-5 were systematically investigated. The thermal decomposition of cubic and tetragonal MOF-5s resulted in the same products: CO2, benzene, amorphous carbon, and crystal ZnO. The thermal decomposition is due to breaking carboxylic bridges between benzene rings and Zn4O clusters. Identifying structural relationships between crystalline and noncrystalline states is of fundamental interest in materials research. Currently, amorphization of solid materials at ambient temperature requires an ultra-high pressure (several GPa). However, this research demonstrated that MOF-5 and IRMOF-8 can be irreversibly amorphized at ambient temperature by employing a low compressing pressure of 3.5 MPa, which is 100 times lower than that required for amorphization of other solids. Furthermore, the pressure-induced amorphization (PIA) of MOFs is strongly dependent on the changeability of bond angles. If the geometric structure of a MOF can allow bond angles to be changed without breaking bonds, it can easily be amorphized by compression. This can explain why MOF-5 and IRMOF-8 can easily be amorphized via compression than Cu-BTC. It is generally recognized that zeolitic imidazolate frameworks (ZIFs) occupy much higher stability than other types of MOFs. The representative of ZIFs is Zn(2-methylimidazole)2 (ZIF-8) exhibiting high-decomposition temperature and high chemical resistance to various solvents. However, so far, it is still unknown whether the high stability of ZIF-8 can be challenged by ions, which is important for its modification by doping ions. In this research, we performed aqueous salt solution treatment on ZIF-8, and the results showed that anions (Cl¯ and NO3¯) in a solution exhibited no effect on the crystal structure of ZIF-8. However, the effect of cations (in a solution) on structure of ZIF-8 strongly depends on the cation valences. The univalent metal cations showed no effect on the structure of ZIF-8, whereas the bivalent or higher-valent metal cations caused the collapse of ZIF-8 crystal structure. Therefore, structure stability of ZIF-8 is considered when it is subjected to the application, in which high-valent metal cations are involved.

Conformational diversity versus nucleic acid triplex stability, a combinatorial study

The stability of a triple helix formed between a DNA duplex and an incoming oligonucleotide strand strongly depends on the solvent conditions and on intrinsic chemical and conformational factors. Attempts to increase triple helix stability in the past included chemical modification of the backbone, sugar ring, and bases in the third strand. However, the predictive power of such modifications is still rather poor. We therefore developed a method that allows for rapid screening of conformationally diverse third strand oligonucleotides for triplex stability in the parallel pairing motif to a given DNA double helix sequence. Combinatorial libraries of oligonucleotides of the requisite (fixed) base composition and length that vary in their sugar unit (ribose or deoxyribose) at each position were generated. After affinity chromatography against their corresponding immobilized DNA target duplex, utilizing a temperature gradient as the selection criterion, the oligonucleotides forming the most stable triple helices were selected and characterized by physicochemical methods. Thus, a series of oligonucleotides were identified that allowed us to define basic rules for triple helix stability in this conformationally diverse system. It was found that ribocytidines in the third strand increase triplex stability relative to deoxyribocytidines independently of the neighboring bases and position along the strand. However, remarkable sequence-dependent differences in stability were found for (deoxy)thymidines and uridines

A meanfield approach to the thermodynamics of a protein-solvent system with application to the oligomerization of the tumor suppressor p53

The thermodynamic stability and oligomerization status of the tumor suppressor p53 tetramerization domain have been studied experimentally and theoretically. A series of hydrophilic mutations at Met-340 and Leu-344 of human p53 were designed to disrupt the hydrophobic dimer–dimer interface of the tetrameric oligomerization domain of p53 (residues 325–355). Meanfield calculations of the free energy of the solvated mutants as a function of interdimer distance were compared with experimental data on the thermal stability and oligomeric state (tetramer, dimer, or equilibrium mixture of both) of each mutant. The calculations predicted a decreasing stability and oligomeric state for the following amino acids at residue 340: Met (tetramer) > Ser Asp, His, Gln, > Glu, Lys (dimer), whereas the experimental results showed the following order: Met (tetramer) > Ser > Gln > His, Lys > Asp, Glu (dimers). For residue 344, the calculated trend was Leu (tetramer) > Ala > Arg, Gln, Lys (dimer), and the experimental trend was Leu (tetramer) > Ala, Arg, Gln, Lys (dimer). The discrepancy for the lysine side chain at residue 340 is attributed to the dual nature of lysine, both hydrophobic and charged. The incorrect prediction of stability of the mutant with Asp at residue 340 is attributed to the fact that within the meanfield approach, we use the wild-type backbone configuration for all mutants, but low melting temperatures suggest a softening of the α-helices at the dimer–dimer interface. Overall, this initial application of meanfield theory toward a protein-solvent system is encouraging for the application of the theoretical model to more complex systems.

Solvent effects on the energy landscapes and folding kinetics of polyalanine

The effect of a solvation on the thermodynamics and kinetics of polyalanine (Ala12) is explored on the basis of its energy landscapes in vacuum and in an aqueous solution. Both energy landscapes are characterized by two basins, one associated with α-helical structures and the other with coil and β-structures of the peptide. In both environments, the basin that corresponds to the α-helical structure is considerably narrower than the basin corresponding to the β-state, reflecting their different contributions to the entropy of the peptide. In vacuum, the α-helical state of Ala12 constitutes the native state, in agreement with common helical propensity scales, whereas in the aqueous medium, the α-helical state is destabilized, and the β-state becomes the native state. Thus solvation has a dramatic effect on the energy landscape of this peptide, resulting in an inverted stability of the two states. Different folding and unfolding time scales for Ala12 in hydrophilic and hydrophobic chemical environments are caused by the higher entropy of the native state in water relative to vacuum. The concept of a helical propensity has to be extended to incorporate environmental solvent effects.