Monitoring Conformation and Protonation States of Glutathione by Raman Optical Activity and Molecular Dynamics.

Glutathione (GSH) is a common antioxidant and its biological activity depends on the conformation and protonation state. We used molecular dynamics, Raman and Raman optical activity (ROA) spectroscopies to investigate GSH structural changes in a broad pH range. Factor analysis of the spectra provided protonation constants (2.05, 3.45, 8.62, 9.41) in good agreement with previously published values. Following the analysis, spectra of differently protonated forms were obtained by extrapolation. The complete deprotonation of the thiol group above pH 11 was clearly visible in the spectra; however, many spectral features did not change much with pH. Experimental spectra at various pH values were decomposed into the simulated ones, which allowed us to study the conformer populations and quality of molecular dynamics (MD). According to this combined ROA/MD analysis conformation of the GSH backbone is affected by the pH changes only in a limited way. The combination of ROA with the computations thus has the potential to improve the MD force field and obtain more accurate populations of the conformer species. The methodology can be used for any molecule, but for a more detailed insight better computational techniques are needed in the future.

Studies of temperature dependent Raman spectroscopy of two nematic liquid crystalline compounds of homologous series.

Raman spectroscopy is an important tool to understand the structural and molecular behaviour of the liquid crystals when they undergo through different temperatures. It also helps to understand the different phase changes of the liquid crystal material as temperature changes. In this work, the structural properties of two nematic liquid crystals having relatively high clearing temperature namely 4 butylcyclohexyl-3, 5-difluoro-4- isothiocyanato biphenyl and 4-pentylcyclohexyl-3, 5-difluoro-4-isothiocyanato biphenyl are studied. The study is done using temperature dependent Raman spectroscopy. From the studies of the two compounds it has been found that the experimental values are agree well with the various functional groups and different bond assignments recorded in literature. This agreement validates the presence of different functional groups and different stretching bonds in the two studied liquid crystal compounds. Deformations of some of the peak positions of the two liquid crystal compounds have been observed with the change in phase at different temperature. Also to understand the behaviour of the Raman peak near the clearing temperatures of the liquid crystal compounds the linewidth of the different peak values at different temperature have also been studied. From the line width study, the various phase transition temperatures of the two liquid crystalline compounds can be confirmed.

Aggregation-aided SERS: Selective detection of arsenic by surface-enhanced Raman spectroscopy facilitated by colloid cross-linking.

Arsenic of natural or industrial origin often occurs in water and makes it impotable. Due to its high toxicity, very sensitive detection is required. In the present study an ultra-sensitive arsenite (As3+) sensing is reported, based on aggregation-aided surface-enhanced Raman scattering (AA-SERS) of modified silver colloids. SERS intensity of mercapto-compounds attached to the colloidal silver nanoparticles surface is greatly increased in the presence of arsenic. Colloid aggregation is facilitated by cross-linking; a meshwork consisting of arsenic atoms and glutathione bridges is formed, as indicated by UV-Vis absorption spectroscopy, TEM and Raman imaging. The best 2-mercaptopyridine reporter molecule makes it possible to directly detect As3+ at concentrations as low as 0.5 ppb, which is better than achieved by the SERS technique so far.

Chiral detection by induced surface-enhanced Raman optical activity.

Combination of optical activity with surface-enhanced Raman scattering has been a dream of physical chemists for a long time. We report a measurement protocol based on silver colloids and aromatic linkers where chiral acids could be detected in concentrations of about 10-5 M. We explain the mechanism by binding and self-assembly of the linkers into chiral aggregates on the silver surface. Following the "sergeants-and-soldiers" principle, the chirality is determined by the relatively minor acidic component. Such detection of biologically relevant molecules may be useful when other methods, such as electronic circular dichroism, are not sensitive enough. In the future, variations of the chemical structure of the linker or other conditions are needed to provide a more specific signal allowing one to better discriminate among the optically active molecules.

Detection and monitoring of in vitro formation of salicylic acid from aspirin using fluorescence spectroscopic technique and DFT calculations.

Acetylsalicylic acid commonly termed as aspirin (AS) is a well known antipyretic and anti-inflammatory drug which can also be used to reduce death risks due to heart attack. In addition to this, it also exhibits some adverse effect such as gastrointestinal, tinnitus, Reye's syndrome. The side effects of AS such as gastrointestinal ulcer, tinnitus and Reye's syndrome are caused due to conversion of AS into its active metabolite salicylic acid (SAL). Conversion of AS into SAL has been investigated generally at basic pH. Since the pH of Gastrointestinal tract is on average neutral ranging from 6.5-7.4. Therefore in the present research work, in vitro conversion of AS to SAL was detected at neutral pH in both aqueous medium and human blood serum samples by time series fluorescence measurements and DFT study. The SAL obtained from AS at neutral pH was observed to be stable for ~ 6 and ~ 4 days in aqueous medium and blood serum, respectively. The mechanism of conversion of AS into SAL was investigated using the transition state theory employing density functional theory (DFT). On the basis of DFT calculation the in vitro formation of SAL from AS at neutral pH was found to involve two intermediate transition states.

Monitoring the in Vitro Thiazolidine Ring Formation of Antioxidant Drug N-Acetyl-l-cysteine at Basic pH and Detection of Reaction Intermediates: A Raman Spectroscopic and Ab Initio Study.

The important cyclization reaction of antioxidant drug N-acetyl-l-cysteine (NAC) has been monitored in vitro at basic pH with the help of time series Raman spectroscopy. The thiazoline ring formation of NAC at acidic pH is a well-known reaction and has been studied extensively. However, the formation of a thiazolidine ring from NAC at basic pH has not been investigated precisely till date. The effect of basicity of the medium on the rate of cyclization has been investigated by studying the reaction at five different basic pH values. Raman signatures of cyclization have been observed with the passage of time and are found to appear faster as the basicity of the medium increases. Ab initio calculations have been done to understand the plausible mechanism of the reaction at basic pH. It is observed that formation of a thiazolidine ring from NAC occurs primarily in four steps, which involve proton abstraction from the thiol (SH) group of NAC and subsequent formation of an S-C bond by a nucleophilic attack of the C-S group on the protonated C-O-H group in NAC. Correlation of the theoretically calculated results with experimental Raman spectral analysis has led to a detailed and proper understanding of this important biochemical reaction.

Temperature dependent polymorphism of pyrazinamide: An in situ Raman and DFT study.

The α and γ polymorphs of drug pyrazinamide have been detected with the help of temperature dependent Raman spectroscopic technique. Pyrazinamide is a very useful drug used for the treatment of tuberculosis (TB) and plays a significant role in destroying the dormant tubercle bacilli which are not destroyed by other common TB drugs. Temperature dependent Raman spectra suggest polymorphic phase change from α→γ form of pyrazinamide between 145 and 146°C. In situ Raman spectra of pyrazinamide between 145 and 146°C show the conversion of α→γ form by the shift in CO stretching vibration accompanied by several other changes. The phase change is characterized by the breaking of two linear NH⋯O type hydrogen bonds associated with CO stretching vibration in α dimer and formation of one linear NH⋯N type hydrogen bond along with a weak intramolecular CH⋯O type hydrogen bond in the γ dimer.

Detection of in Vitro Metabolite Formation of Leflunomide: A Fluorescence Dynamics and Electronic Structure Study.

The metabolic transformation of antirheumatic fluorescent drug leflunomide into its active metabolite teriflunomide through isoxazole ring opening has been monitored in vitro using steady state and time domain fluorescence spectroscopy and density functional theory. During metabolic reaction, absorption of leflunomide split into two bands resembling absorption spectra of teriflunomide. The fluorescence spectra reveal slow conversion of leflunomide to E and Z forms of teriflunomide in aqueous medium, which becomes faster at basic pH. The E form, which is more potent as a drug, becomes more stable with an increase in the basicity of the medium. Both molecules are associated with charge transfer due to twisting in the lowest singlet excited state. Excited state charge transfer followed by proton transfer was also observed in the Z form during the ring opening of leflunomide. Quantum yield and radiative decay rates have been observed to decrease for the metabolite because of an increase in nonradiative decay channels.

Spectroscopic and structural study of the newly synthesized heteroligand complex of copper with creatinine and urea.

Study of copper complex of creatinine and urea is very important in life science and medicine. In this paper, spectroscopic and structural study of a newly synthesized heteroligand complex of copper with creatinine and urea has been discussed. Structural studies have been carried out using DFT calculations and spectroscopic analyses were carried out by FT-IR, Raman, UV-vis absorption and fluorescence techniques. The copper complex of creatinine and the heteroligand complex were found to have much increased water solubility as compared to pure creatinine. The analysis of FT-IR and Raman spectra helps to understand the coordination properties of the two ligands and to determine the probable structure of the heteroligand complex. The LIBS spectra of the heteroligand complex reveal that the complex is free from other metal impurities. UV-visible absorption spectra and the fluorescence emission spectra of the aqueous solution of Cu-Crn-urea heteroligand complex at different solute concentrations have been analyzed and the complex is found to be rigid and stable in its monomeric form at very low concentrations.

Temperature dependent Raman and DFT study of creatine.

Temperature dependent Raman spectra of creatine powder have been recorded in the temperature range 420-100K at regular intervals and different clusters of creatine have been optimized using density functional theory (DFT) in order to determine the effect of temperature on the hydrogen bonded network in the crystal structure of creatine. Vibrational assignments of all the 48 normal modes of the zwitterionic form of creatine have been done in terms of potential energy distribution obtained from DFT calculations. Precise analysis gives information about thermal motion and intermolecular interactions with respect to temperature in the crystal lattice. Formation of higher hydrogen bonded aggregates on cooling can be visualized from the spectra through clear signature of phase transition between 200K and 180K.

Effect of deuteration on hydrogen bonding: a comparative concentration dependent Raman and DFT study of pyridine in CH3OH and CD3OD and pyrimidine in H2O and D2O.

The relative effect of hydrogen bonding of pyrimidine (Pyr) in H(2)O/D(2)O and pyridine (Py) in CH(3)OH/CD(3)OD has been analyzed using Raman Difference Spectroscopic (RDS) technique and DFT calculations. This study is focused on analyzing the concentration dependent variation of linewidth, peak position and intensity of ring breathing mode of Py and Pyr. The ring breathing mode of Pyr in H(2)O and D(2)O has three components; due to free Pyr, lighter complexes of mPyr+nH(2)O/D(2)O and heavier complexes of mPyr+nH(2)O/D(2)O. The pyridine molecules, however, show only two components in CH(3)OH and CD(3)OD. Of these two components, one corresponds to free Py and the other inhomogeneously broadened profile corresponds to all mPy+nCH(3)OH/CD(3)OD complexes. The variation of peak position and linewidth establishes the role of dipole moment of complexes and the diffusion in the mixture. In case of CD(3)OD solution splitting was observed in ∼1030 cm(-1) band of Py, where an additional band at ∼1034 cm(-1) appears at x(Py) ≤ 0.4. However, this band remains single at all concentrations in case of CH(3)OH solvent.