Biomedical subjects
Publications and source records attributed to V Subramanian.
Ab initio calculations at the second-order Møller-Plesset perturbation theoretic level have been carried out to study the solvation of protonated water by phenol molecules. The results show that in addition to classical O-H...O hydrogen bonds, C-H...O, pi...H-O, and pi...H-C bonds are also formed, thus stabilizing the H3O+(C(6)H(5)OH)3 complex.
A molecular dynamics (MD) simulation study has been carried out to understand the stability of the triple helical collagen models. The calculations show that the presence of the aspartic acid residue in different positions leads to the local variation in the structure. Analyses of root-mean-square deviation (RMSD), radial distribution function (RDF), puckering effect, dihedral angle variation, hydrogen bond (H-bond), and conformational changes during molecular dynamics simulation reveal that the local perturbation in the sequences, increase in chain flexibility due to removal of five membered rings in the collagen by aspartic acid, change of intermolecular H-bonding pattern, and differences in the association of water are mainly influencing the nature of stabilization of collagen by aspartic acid.
Our objective was to determine whether electrical neuromodulation using spinal cord stimulation (SCS) mitigates transient ischemia-induced ventricular infarction and, if so, whether adrenergic neurons are involved in such cardioprotection. The hearts of anesthetized rabbits, subjected to 30 min of left anterior descending coronary arterial occlusion (CAO) followed by 3 h of reperfusion (control), were compared with those with preemptive SCS (starting 15 min before and continuing throughout the 30-min CAO) or reactive SCS (started at 1 or 28 min of CAO). For SCS, the dorsal C8-T2 segments of the spinal cord were stimulated electrically (50 Hz, 0.2 ms, 90% of motor threshold). For preemptive SCS, separate groups of animals were pretreated 15 min before SCS onset with 1) vehicle, 2) prazosin (alpha(1)-adrenoceptor blockade), or 3) timolol (beta-adrenoceptor blockade). Infarct size (IS), measured with tetrazolium, was expressed as a percentage of risk zone. In controls exposed to 30 min of CAO, IS was 36.4 +/- 9.5% (SD). Preemptive SCS reduced IS to 21.8 +/- 6.8% (P < 0.001). Preemptive SCS-mediated infarct reduction was eliminated by prazosin (36.6 +/- 8.8%) and blunted by timolol (29.4 +/- 7.5%). Reactive SCS did not reduce IS. SCS increased phosphorylation of cardiac PKC. SCS did not alter blood pressure or heart rate. We conclude that preemptive SCS reduces the size of infarcts induced by transient CAO; such cardioprotection involves cardiac adrenergic neurons.
The environmental effects of chloroanilines depend on their physical and chemical properties, and it is therefore important to know their structure-property relationships that allow a complete understanding of their environmental consequences. The chemical reactivity profiles of all 19 chloroanilines have been investigated using the density functional theory for the first time. Global reactivity descriptors, such as hardness, chemical potential, electrophilicity index, and polarizability, and local reactivity descriptors, namely, local philicities, have been calculated in order to gain insights into the reactive nature and the reactive sites of the selected systems. Using AIM theory, the presence of hydrogen bond critical points (HBCPs) and the values of electron density and Laplacian of electron density at the HBCPs have been analyzed to appreciate the presence of intramolecular hydrogen bonding in the selected systems. Structure-toxicity analysis of the selected set of chloroanilines demonstrates the importance of the electrophilicity index in the prediction of reactivity/toxicity.
Molecular orbital calculations have been performed on thiophene oligomers bearing heterocyclic substituents at the third position in order to understand the interplay of effects such as the nature of substituent, skeletal substitution pattern, heteroatom identity, etc. on electronic transitions. The geometry optimization was carried out using the semiempirical AM1 method, and the electronic transitions predicted for the oligomers were extrapolated for polymers using an oligomeric approach. The experimentally determined optical transitions were found to follow the predicted trend of electronic transitions of monomers and polymers.
The toxicological structure-activity relationships are investigated using conceptual DFT based descriptors like global and local electrophilicities. In the present work the usefulness of electrophilicity in predicting toxicity of several polyaromatic hydrocarbons (PAH) is assessed. The toxicity is expressed through biological activity data (pIC50) defined as molar concentration of those chemicals necessary to displace 50% of radiolabeled tetrachlorodibenzo-p-dioxin (TCDD) from the arylhydrocarbon (Ah) receptor. The experimental toxicity values (pIC50) for the electron acceptor toxin like polychlorinated dibenzofurans (PCDF) are taken as dependent variables and the DFT based global descriptor electrophilicity index (omega) is taken as independent variable in the training set. The same model is then tested on a test set of polychlorinated biphenyls (PCB). A good correlation is obtained which vindicates the importance of these descriptors in the QSAR studies on toxins. These toxins act as electron acceptors in the presence of biomolecules whereas aliphatic amines behave as electron donors some of which are also taken into account for the present work. The toxicity values of the aliphatic amines in terms of the 50% inhibitory growth concentration (IGC50) towards ciliate fresh-water protozoa Tetrahymena pyriformis are considered. Since there is no global nucleophilicity we apply local nucleophilicity (omegamax+) as the descriptor in this case of training set. The same regression model is then applied to a test set of amino alcohols. Although the correlation is very good the statistical analysis reflects some cross validation problem. As a further check the amines and amino alcohols are used together to form both the training and the test sets to provide good correlation. It is demonstrated that the toxicity of several toxins (both electron donors and acceptors) in the gas and solution phases can be adequately explained in terms of global and local electrophilicities. Amount of charge transfer between the toxin and the biosystem, simulated as nucleic acid bases and DNA base pairs, indicates the importance of charge transfer in the observed toxicity. The major strength of the present analysis vis-à-vis the existing ones rests on the fact that it requires only one descriptor having a direct relationship with toxicity to provide a better correlation. Importance of using the information from both the toxin and the biosystem is also analyzed.
Structural transformations at the TiO2Pt and TiO2Ir interfaces during UV-irradiation have been probed by X-ray absorption spectroscopy. Oxidation by the photogenerated holes results in the intercalation of Pt and Ir into the Titania matrix. The structural transformations observed with Pt and Ir nanoparticles anchored on TiO2 is different than the clustering of gold atoms observed in the TiO2/Au system. Implications of such structural transformations on the photocatalytic activity of semiconductor photocatalyts are discussed.
Acid-base dissociation constants (pK(a) values) are important in understanding the chemical, environmental and toxicological properties of molecules. Though various methods have been developed to predict pK(a) by experimental and theoretical models, prediction of pK(a) is still complicated. Hence, a new approach for predicting pK(a) using the group philicity concept has been attempted. Presence of known functional groups in a molecule is utilized as the most important indicator to predict pK(a). The power of this descriptor in describing pK(a) for the series of carboxylic acids, various substituted phenols, anilines, phosphoric acids, and alcohols is probed. Results reveal that the group electrophilicity is suitable for effectively predicting the pK(a) values.
Hartree-Fock (HF) calculations using 6-31G*, 6-311++G(d,p), aug-cc-pVDZ, and aug-cc-pVTZ basis sets show that hydrogen peroxide molecular clusters tend to form hydrogen-bonded cyclic and cage structures along the lines expected of a molecule which can act as a proton donor as well as an acceptor. These results are reiterated by density functional theoretic (DFT) calculations with B3LYP parametrization and also by second-order Møller-Plesset perturbation (MP2) theory using 6-31G* and 6-311++G(d,p) basis sets. Trends in stabilization energies and geometrical parameters obtained at the HF level using 6-311++G(d,p), aug-cc-pVDZ, and aug-cc-pVTZ basis sets are similar to those obtained from HF/6-31G* calculation. In addition, the HF calculations suggest the formation of stable helical structures for larger clusters, provided the neighbors form an open book structure.
We demonstrate the high-rate capability of lithium ion insertion-deinsertion reactions in carbon nanofibers (CNFs). The morphology of CNFs with structural and surface defects, due to the mixed features of disordered and graphitic carbon, plays an important role in both the enhancement of the lithium ion storage and the rate-determining reactions during the topotactic process. The reversible specific capacity of the CNFs at a 0.1 C rate was 461 mA x h/g. The most promising property, which is expected to overcome the hurdles of lithium batteries for high-power applications, is that they deliver considerably high specific capacity even at a very high charge-discharge current, i.e., at a cycling rate of 10 C the reversible capacity is around 170 mA x h/g with a 95% Coulombic efficiency.
OBJECTIVE: To study the role of beta1 integrins in left ventricular (LV) remodelling after myocardial infarction (MI). METHODS AND RESULTS: LV structural and functional alterations were determined in wild-type (WT) and beta1 integrin heterozygous knockout (hKO) mice one month after MI. MI increased beta1 integrin expression in both groups; however, the increase was lower in hKO. Infarct size was similar in WT and hKO mice, whereas lung wet weight to dry weight ratio was increased in the hKO-MI mice (5.17 (SE 0.13) v 4.60 (0.15) in WT-MI, p < 0.01). LV end systolic and end diastolic diameters were significantly higher and percentage fractional shortening was significantly lower in hKO-MI. The ratio of peak velocity of early LV filling (E wave) to that of the late LV filling (A wave) and the isovolumic relaxation time (IVRT) were increased in both MI groups but the increase in IVRT was significantly higher in hKO-MI group than in WT-MI mice. Langendorff perfusion analysis indicated reduced peak LV developed pressure and increased LV end diastolic pressure in both MI groups. The reduction in peak LV developed pressure (36.7 (2.2) v 53.4 (1.9) mm Hg, p < 0.05) and increase in LV end diastolic pressure was higher in hKO-MI than in WT-MI. Increase in fibrosis was not different between the two MI groups. The increase in myocyte circumference was higher in the hKO-MI group (p < 0.001 v WT-MI). The number of apoptotic myocytes was significantly higher in hKO-MI than in WT-MI mice (p < 0.005) three days after MI. The number of necrotic myocytes was not different between the two MI groups. CONCLUSION: beta1 integrins are crucial in post-MI remodelling with effects on LV function, hypertrophy and apoptosis.
It is shown that the electron density at the hydrogen bond critical point increases approximately linearly with increasing stabilization energy in going from weak hydrogen bonds to moderate and strong hydrogen bonds, thus serving as an indicator of the nature and gradual change of strength of the hydrogen bond for a large number of test intermolecular complexes.
We present a comprehensive analysis to probe the effect of solvation on the reactivity of the complete series of chlorobenzenes through the conceptual density functional theory (DFT)-based global and local descriptors. We propose a multiphilic descriptor in this study to explore the nature of attack at a particular site in a molecule. It is defined as the difference between nucleophilic and electrophilic condensed philicity functions. This descriptor is capable of explaining both the nucleophilicity and electrophilicity of the given atomic sites in the molecule simultaneously. The predictive ability of this descriptor is tested on the complete series of chlorobenzenes in gas and solvent media. A structure-toxicity analysis of these entire sets of chlorobenzenes toward aquatic organisms demonstrates the importance of the electrophilicity index in the prediction of the reactivity/toxicity.
The philicity concept [J. Phys. Chem. A 2003, 107, 4973] is put in proper perspective. In the present work we analyze different physicochemical problems using philicity. It provides satisfactory results in all such cases. We also compare the relative electro(nucleo)philicity with philicity to show that philicity is better than relative electro(nucleo)philicity when the intermolecular reactivity trends are considered and there is hardly any preference of one above the other as far as the intramolecular reactivities are concerned. On the contrary, the philicity concept has some advantages over the other concept.
BACKGROUND: This systematic review examined the use of immunomodulators and the risk of postoperative complications after abdominal surgery in patients with inflammatory bowel disease. METHODS: Electronic databases (PubMed, Embase, Ingenta, Zetoc and Ovid) were searched and the reference lists in all articles identified were hand-searched for further relevant papers. Studies were included if they evaluated postoperative complications and defined exposure to individual immunomodulators. RESULTS: All 11 studies that met the inclusion criteria were observational studies; two were reported only in abstract form. Five studies reported risks associated with azathioprine, five reported risks associated with cyclosporin and three reported risks associated with infliximab. None showed an increased risk of either total or infectious complications associated with immunomodulator use. However, subgroup analysis in one study, published as an abstract, suggested increased rates of anastomotic complications and reoperation associated with azathioprine. CONCLUSION: Available evidence does not suggest an increased rate of postoperative complications associated with immunomodulator use.
The search for the best quantitative structure-activity relationship (QSAR) models in ecotoxicology is an ever-topical research activity. Hence, the development of new descriptors and applying them successfully in QSAR studies seems demanding in ecotoxicology. In the present work, group philicities are utilized for the first time in QSAR analysis for ecotoxicological studies on chlorophenols (CPs). It is important to point out that group philicities are capable of providing the best QSAR model for the toxicity of CPs against Daphnia magna. Furthermore, global electrophilicity and group philicities together give the best QSAR models for Brachydanio rerio and Bacillus with the maximum value of coefficient of determination and high internal predictive ability. The developed QSAR models clearly show the importance of the selected density functional reactivity indices as descriptors in ecotoxicological studies.
The model white rot fungus Phanerochaete chrysosporium has the extraordinary ability to degrade (to CO(2)) lignin and detoxify a variety of chemical pollutants. Whole genome sequencing of this fungus has revealed the presence of the largest P450ome in fungi comprising approx. 150 P450 genes, most of which have unknown function. On the basis of our genome-wide structural and evolutionary analysis, these P450 genes could be classified into 12 families and 23 subfamilies and under 11 fungal P450 clans. The analysis further revealed an extensive gene clustering with a total of 16 P450 clusters constituted of up to 11 members per cluster. In particular, evidence and role of gene duplications and horizontal gene transfer in the evolution of these P450 clusters have been discussed using two of the P450 families [CYP63 and CYP505 (where CYP is cytochrome P450)] as examples. In addition, the observed differential transcriptional induction of the clustered members of the CYP63 gene family, in response to different xenobiotic chemicals and carbon sources, indicated functional divergence within the P450 clusters, of this basidiomycete fungus.
Thermal 6pi electrocyclization of cyclononatetraene (CNT), its hetero-substituted analogues, and its benzannelated derivatives have been investigated by using the B3LYP method employing 6-31G* and 6-311+G** basis sets. The results indicate that heterosubstitution and benzannelation influence the rate of cyclization. Nucleus independent chemical shifts (NICS), conceptual density functional theory (DFT) based reactivity descriptors, group electronegativity values, and barriers to planarity provide complementary evidence for the predicted rate of cyclization. The available experimental data are in good agreement with the computed values.