Influence of the Substituents on the CH...π Interaction: Benzene–Methane Complex

Recently we showed that the binding energy of the benzene...acetylene complex could be tuned up to 5 kcal/mol by substituting the hydrogen atoms of the benzene molecule with multiple electron-donating/electron-withdrawing groups (<i>J. Chem. Theory Comput.</i> <b>2012</b>, <i>8</i>, 1935). In continuation, we have here examined the influence of various substituents on the CH...π interaction present in the benzene...methane complex using the CCSD­(T) method at the complete basis set limit. The influence of multiple fluoro substituents on the interaction strength of the benzene...methane complex was found to be insignificant, while the interaction strength linearly increases with successive addition of methyl groups. The influence of other substituents such as CN, NO₂, COOH, Cl, and OH was found to be negligible. The NH₂ group enhances the binding strength similarly to the methyl group. Energy decomposition analysis predicts the dispersion energy component to be on an average three times larger than the electrostatic energy component. Multidimensional correlation analysis shows that the exchange-repulsion and dispersion terms are correlated very well with the interaction distance (<i>r</i>) and with a combination of the interaction distance (<i>r</i>) and molar refractivity (MR), while the electrostatic component correlates well when the Hammett constant is used in combination with the interaction distance (<i>r</i>). Various recently developed DFT methods were used to assess their ability to predict the binding energy of various substituted benzene...methane complexes, and the M06-2X, B97-D, and B3LYP-D3 methods were found to be the best performers, giving a mean absolute deviation of ∼0.15 kcal/mol

Tuning the C–H···π Interaction by Different Substitutions in Benzene–Acetylene Complexes

The influence of substitutions in aromatic moieties on the binding strength of their complexes is a subject of broad importance. Using a set of various substituted benzenes, Sherrill and co-workers (J. Am. Chem. Soc. 2011, 133, 13244; J. Phys. Chem. A 2003, 107, 8377) recently showed that the strength of a stacking interaction (π···π interaction) is enhanced by adding substituents regardless of their nature. Although the binding strength of an activated C–H···π interaction is comparable to that of a stacking interaction, a similar systematic study is hitherto unknown in the literature. We have computed the stabilization energies of the C–H···π complex of acetylene and multiple fluoro-/methyl-substituted benzenes at the coupled-cluster single and double (triple) excitation [CCSD­(T)]/complete basis set (CBS) limit. The trend for interaction energies was found to be hexafluorobenzene–acetylene < <i>sym</i>-tetrafluorobenzene–acetylene < <i>sym</i>-trifluorobenzene–acetylene < <i>sym</i>-difluorobenzene–acetylene < benzene–acetylene < <i>sym</i>-dimethylbenzene–acetylene < <i>sym</i>-trimethylbenzene–acetylene < <i>sym</i>-tetramethylbenzene–acetylene < hexamethylbenzene–acetylene. Therefore, contrary to the case of stacking interaction (Hohenstein et al. J. Am. Chem. Soc. 2011, 133, 13244), we show here that electron-withdrawing groups weaken the dimer while electron-donating groups strengthen the interaction energy of the dimer. Various recently developed density functional theoretic (DFT) methods were assessed for their performance and the M05-2X, M06-2X, and ωB97X-D methods were found to be the best performers. These best DFT performers were employed in determining the influence of other representative substituents (-NO₂, -CN, -COOH, -Br, -Cl, -OH, and -NH₂) as an extension to the above work. The results for the complex of acetylene and various para-disubstituted benzenes revealed a trend in binding energies that is in accordance with the ring-activating/deactivating capacity of each of these groups. The stabilization energy was partitioned via the DFT symmetry-adapted perturbation theory (SAPT) method, and both dispersion and electrostatic interactions were seen to be major driving forces for the complex stabilization. Interestingly, the sum of the energy contributors such as dispersion, exchange, induction, etc., is close to zero and the total energy follows the trend of the electrostatic energy. We observe an excellent linear correlation between the optimized intermolecular separation of the different complexes and the exchange/dispersion interaction

Stacking and Spreading Interaction in N-Heteroaromatic Systems

π−π interactions in heteroaromatic systems are ubiquitous in biological systems. In the present study, stabilization energies of stacked and hydrogen-bonded dimers of N-heteroaromatic systems (pyridine, pyrazine, <i>sym</i>-triazine, and <i>sym</i>-tetrazine) have been computed using a benchmark quality coupled cluster through the perturbative triples (CCSD(T)) method at the estimated complete basis set (CBS) limit. In the case of stacking, monomer units are found to be stacked in parallel planes with displaced geometries. The stabilization energies for the most stable stacked geometry of pyridine, pyrazine, <i>sym</i>-triazine, and <i>sym</i>-tetrazine dimers are found to be −3.39, −4.14, −4.02, and −3.90 kcal/mol, respectively at the est. CCSD(T)/CBS level of theory, which is clearly larger than the stabilization energy for the most stable geometry of the benzene dimer. In the case of spreading, hydrogen bonded dimers and trimers are stabilized by weak C−H···N interactions. The stabilization energies for the stacked and the spread out complexes are found to be comparable. The stabilization energy for the trimers is computed using the MP2, MP3, and B3LYP-D methods. The present study is aimed at unraveling the basis of preferred conformations of N-heteroaromatic dimers. These model systems explain partly the stability of double helical DNA and RNA structures that are formed by stacking and hydrogen bonding between nucleic acid bases

Image_2_TCF7L2 gene associated postprandial triglyceride dysmetabolism- a novel mechanism for diabetes risk among Asian Indians.tif

AimTCF7L2 gene is believed to increase the risk of T2DM by its effects on insulin secretion. However, the exact mechanism of this enhanced risk is not clearly known. While TCF7L2 gene has been shown to affect lipid metabolism, these effects have remained largely unexplored in the context of diabetes risk.MethodsPostprandial lipid responses to a standardized fat challenge test were performed in 620 Asian Indian subjects (310 with NGT and 310 with T2DM/prediabetes) and compared between the risk and wild genotypes of the rs7903146 TCF7L2 gene. In 30 subjects scheduled to undergo abdominal surgery (10 each with NGT, Prediabetes and T2DM), adipocyte TCF7L2 gene expression was also performed by real time qPCR and confirmed by protein expression in western blot.ResultsT allele of rs7903146 TCF7L2 gene was confirmed as the risk allele for T2DM (OR=1.8(1.2-2.74), p=0.005). TT+CT genotypes of rs7903146 TCF7L2 gene showed significantly higher 4hrTg (pConclusionThere is significant PPTg dysmetabolism associated with the risk allele of rs7903146 polymorphism as well as adipocyte expression of TCF7L2 gene. Significant upregulation of TCF7L2 gene expression in VAT that correlates with PPTg and glycaemia is also seen in Asian Indians with glucose intolerance. Modulation of PPTg metabolism by TCF7L2 gene and the resultant PPHTg may be a novel mechanism that contributes to its diabetes risk in them.</p