Biomedical subjects
Publications and source records attributed to R Parthasarathi.
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.
BACKGROUND: The phenomenal progress of minimally invasive surgery has imparted its influence on conventional esophagectomy. Currently, more esophagectomies are being performed by laparoscopic and/or thoracoscopic methods. Esophagogastrectomy for the adenocarcinoma of the gastroesophageal (GE) junction has been a conventional treatment. The literature is limited regarding the laparoscopic approach to esophagogastrectomy. The aim of this study was to evaluate the outcome of laparoscopic esophagogastrectomy in the management of adenocarcinoma of the GE junction. METHODS: From January 1997 to February 2005, laparoscopic esophagogastrectomy was performed in 32 patients. Indication for operation was adenocarcinoma of the GE junction in all patients. Neo-adjuvant therapy was used in two patients (6.88%) only. Initially, our approach to intrathoracic anastomosis without thoracic and cervical access was to introduce the anvil of circular stapler through minilaparotomy incision (n = 22), but later we switched to trans-oral placement of anvil into the distal end of the esophagus (n = 10). RESULTS: There were 22 men and 10 women. Median age was 61.8 years (range, 39-72). There was no conversion. The laparoscopic esophagogastrectomy was completed in all patients. The pyloromyotomy and feeding jejunostomy were performed in all cases. The median intensive care unit stay was 1 day (range, 1-28); hospital stay was 7 days (range, 5-42). Mean estimated blood loss and mean operative time were 150 ml and 200 min, respectively. At mean follow-up of 14 months (range, 2-40), stage-specific survival was similar to that of other series. CONCLUSION: In selected cases of adenocarcinoma of the GE junction, laparoscopic esophagogastrectomy offers as good as or better results than open operation in our institution with extensive advance endoscopic and open experience. This study shows that laparoscopic esophagogastrectomy has potential to meet oncologic criteria of clearance and provide the benefits of minimally invasive surgery as well.
Folding and solubility of proteins are dependent on their state of hydration. How does a protein-bovine serum albumin (BSA) behave in the presence of Hofmeister electrolytes, especially at interfaces? Langmuir films of bovine serum albumin (BSA) in the presence of different Hofmeister electrolytes at air/solution interface and as Langmuir-Blodgett films (LB films) at solid/solution interface have been studied using the surface pressure-molecular area (pi-A) isotherms and surface energy parameters. Changes in secondary structure have been analyzed using circular dichroism (CD) and fluorescence spectroscopy. Hydrodynamically coupled water fraction of BSA in different environments has been estimated using quartz crystal microbalance (QCM) and related to the secondary structural changes. Molecular modeling of BSA in different environments showed that the protein has a compact structure at the interface compared to vacuum. The contact areas estimated using molecular modeling agreed with the experimental results. The results show that the properties of BSA at the interface follow the Hofmeister series with NaF leading to maximum compaction in the protein. Further, in addition to ion specific solvation and different ion size, water structure alteration and the bound water fractions contribute importantly to the Hofmeister effect.
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.
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.
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.
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 structure and chemical reactivity profiles of all 12 chlorobenzenes have been investigated using the density functional theory and ab initio molecular orbital calculations. Global and local reactivity descriptors such as electrophilicity index and local philicity, respectively, of the selected systems have been calculated in order to gain insights into the reactive nature and the reactive sites of these compounds. Also, the effects of chlorine substitution on the aromaticity of the compounds have been analyzed by calculating the nucleus-independent chemical shift. Interaction through charge transfer between chlorobenzenes and nucleic acid bases/selected base pairs are determined using Parr's formula. The results revealed that the chlorobenzenes act as electron acceptors in their interaction with biomolecules. Structure-toxicity analysis of this entire set of chlorobenzenes demonstrates the importance of the electrophilicity index in the prediction of reactivity/toxicity.
Color tuning by the tailoring of substituents at the 3-position of thiophene is very encouraging, and comparative experimental and theoretical studies proved to be powerful in the search for a suitable design for the above. Since the novel polythiophene-based materials substituted with five-membered/six-membered ring containing sulphur and nitrogen at different positions are proven to be potential candidates for electron-transporting hole blocking functions, the structure-property relationship of these systems have been focused in the present study. Molecular-orbital calculations are applied to obtain the optimized geometries and band gaps of the thiophene oligomers. An oligomeric approach has been implemented for calculating the band gaps, and the theoretically obtained band gaps for the different model compounds are compared. Density-functional theory B3LYP6-31G* predicted band-gap values are compared with the experimental band gaps obtained from optical-absorption edge. The predicted values show little deviations from experimental band gaps, but the trend in band gap is found to be the same in experimental and theoretical results in most of the cases. Hence, this study illustrates the usefulness of quantum-mechanical calculations in understanding the effects of various structural parameters on optical band gap.
The logarithmic n-octanol/water partition coefficient (logK(ow)) is an important property for pharmacology, toxicology and medicinal chemistry. Quantitative structure-property relationship (QSPR) model for the lipophilic behaviour (logK(ow)) of the data set containing 133 polychlorinated biphenyl (PCB) congeners is analyzed using the conceptual density functional theory based global reactivity parameter such as electrophilicity index (omega) along with energy of lowest unoccupied molecular orbital (E(LUMO)) and number of chlorine substituents (N(Cl)) as descriptors. A reasonably good coefficient of determination (r(2) = 0.914) and the internal predictive ability (r(cv)(2) = 0.909) values are obtained indicating the significance of the considered descriptors in the property analysis of PCBs. Further, the developed method has widespread applicability from chemical reactivity to toxicity analysis and in studies related to various physicochemical properties in the series of dioxins and other polyaromatic hydrocarbons.
Ab initio calculations suggest the possibility of forming boric acid clusters in the laboratory. The most stable form of the boric acid dimer contains two hydrogen bonds, similar to the carboxylic acid dimers. Though the trimer and the tetramer form extensions of this geometry, the pentamer prefers a bowl shape. Any addition of boric acid molecules to this geometry leads to bowl-shaped structures with the 15-mer forming a (3/4)buckyball and the 20-mer a full-fledged buckyball. The hexamer, on the other hand, prefers to stay planar as a hexagon-centered rosette. Any further extension of this geometry leads to planar structures as long as a pentagon is not included.
Electrophilicity is one of the cardinal chemical reactivity descriptors successfully employed in various molecular reactivity studies within a structure-activity relationship parlance. The applications of this quantity in the modeling of toxicological properties have inspired us to perform a more exhaustive study in order to test and/or to validate the application of electrophilicity in assessing its chemical and toxicological potential. For this reason the toxicity of a large data set of molecules comprising 252 aliphatic compounds on the Tetrahymena pyriformis is studied. A quantitative structure-activity relationship analysis enabled us to model toxicity in terms of global and local electrophilicities, which provide a reasonably good prediction of aliphatic toxicity. It is heartening to note that the global and local electrophilicity values together can explain the toxicity of a large variety of aliphatic compounds nicely without resorting to any other descriptor or other microscopic/macroscopic physicochemical properties as is the situation in all other QSAR studies.