Charge transfer complex formation between TX-100/CCl4 reverse micelle and a series of π-electron acceptors: determination of cmc and aggregation number

Electron donor–acceptor interaction of the reverse micelle (RM) of TX-100 in CCl₄ medium with a number of π-acceptors has been established by analysing the charge transfer (CT) absorption bands in the light of Mulliken's theory. Aggregation number (n) and operational critical micellisation concentration of the RM and formation constants of the RM–p-chloranil and RM-o-chloranil complexes have been determined by UV-visible spectrophotometry. Values of n thus obtained (20–30) are close to that of TX-100/cyclohexane dry reverse micelles determined by other methods and also to a theoretically calculated value of n for AOT/CCl₄ dry RM.     

Anomalous power law decay in solvation dynamics of DNA: a mode coupling theory analysis of ion contribution

Several time dependent fluorescence Stokes shift (TDFSS) experiments have reported a slow power law decay in the hydration dynamics of a DNA molecule. Such a power law has neither been observed in computer simulations nor in some other TDFSS experiments. Here we observe that a slow decay may originate from collective ion contribution because in experiments DNA is immersed in a buffer solution, and also from groove bound water and lastly from DNA dynamics itself. In this work we first express the solvation time correlation function in terms of dynamic structure factors of the solution. We use mode coupling theory to calculate analytically the time dependence of collective ionic contribution. A power law decay in seen to originate from an interplay between long-range probe–ion direct correlation function and ion–ion dynamic structure factor. Although the power law decay is reminiscent of Debye–Falkenhagen effect, yet solvation dynamics is dominated by ion atmosphere relaxation times at longer length scales (small wave number) than in electrolyte friction. We further discuss why this power law may not originate from water motions which have been computed by molecular dynamics simulations. Finally, we propose several experiments to check the prediction of the present theoretical work.     

Dynamic coupling between the LID and NMP domain motions in the catalytic conversion of ATP and AMP to ADP by adenylate kinase

The catalytic conversion of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) to adenosine diphosphate (ADP) by adenylate kinase (ADK) involves large amplitude, ligand induced domain motions, involving the opening and the closing of ATP binding domain (LID) and AMP binding domain (NMP) domains, during the repeated catalytic cycle. We discover and analyze an interesting dynamical coupling between the motion of the two domains during the opening, using large scale atomistic molecular dynamics trajectory analysis, covariance analysis, and multidimensional free energy calculations with explicit water. Initially, the LID domain must open by a certain amount before the NMP domain can begin to open. Dynamical correlation map shows interesting cross-peak between LID and NMP domain which suggests the presence of correlated motion between them. This is also reflected in our calculated two-dimensional free energy surface contour diagram which has an interesting elliptic shape, revealing a strong correlation between the opening of the LID domain and that of the NMP domain. Our free energy surface of the LID domain motion is rugged due to interaction with water and the signature of ruggedness is evident in the observed root mean square deviation variation and its fluctuation time correlation functions. We develop a correlated dynamical disorder-type theoretical model to explain the observed dynamic coupling between the motion of the two domains in ADK. Our model correctly reproduces several features of the cross-correlation observed in simulations.     

Revealing the metabolic sites of atazanavir in human by parallel administrations of D‐atazanavir analogs

Atazanavir (Reyataz^®) is an important member of the HIV protease inhibitor class. Because of the complexity of its chemical structure, metabolite identification and structural elucidation face serious challenges. So far, only seven non‐conjugated metabolites in human plasma have been reported, and their structural elucidation is not complete, especially for the major metabolites produced by oxidations. To probe the exact sites of metabolism and to elucidate the relationship among in vivo metabolites of atazanavir, we designed and performed two sets of experiments. The first set of experiments was to determine atazanavir metabolites in human plasma by LC‐MS, from which more than a dozen metabolites were discovered, including seven new ones that have not been reported. The second set involved deuterium labeling on potential metabolic sites to generate D‐atazanavir analogs. D‐atazanavir analogs were dosed to human in parallel with atazanavir. Metabolites of D‐atazanavir were identified by the same LC‐MS method, and the results were compared with those of atazanavir. A metabolite structure can be readily elucidated by comparing the results of the analogs and the pathway by which the metabolite is formed can be proposed with confidence. Experimental results demonstrated that oxidation is the most common metabolic pathway of atazanavir, resulting in the formation of six metabolites of monooxidation (M1, M2, M7, M8, M13, and M14) and four of dioxidation (M15, M16, M17, and M18). The second metabolic pathway is hydrolysis, and the third is N‐dealkylation. Metabolites produced by hydrolysis include M3, M4, and M19. Metabolites formed by N‐dealkylation are M5, M6a, and M6b. Copyright © 2013 John Wiley & Sons, Ltd.     

Molecular interpretation of the linear relationship between the entropy and the enthalpy of activation of charge transfer reactions in polar liquids

The well-known linear relationship (TΔS# =αΔH# +β, where 1 >α > 0,β > 0) between the entropy (ΔS#) and the enthalpy (ΔH#) of activation for reactions in polar liquids is investigated by using a molecular theory. An explicit derivation of this linear relation from first principles is presented for an outersphere charge transfer reaction. The derivation offers microscopic interpretation for the quantitiesα andβ. It has also been possible to make connection with and justify the arguments of Bell put forward many years ago     

Ionic and dipolar solvation dynamics in liquid water

The solvation time correlation function for solvation in liquid water was measured recently. The solvation was found to be very fast, with a time constant equal to 55 fs. In this article we present theoretical studies on solvation dynamics of ionic and dipolar solutes in liquid water, based on the molecular hydrodynamic approach developed earlier. The molecular hydrodynamic theory can successfully predict the ultrafast dynamics of solvation in liquid water as observed from recent experiments. The present study also reveals some interesting aspects of dipolar solvation dynamics, which differs significantly from that of ionic solvation. Dedicated to Prof. C N R Rao on his 60th birthday