Theoretical study of the conformational energy hypersurface of cyclotrisarcosyl

The multidimensional Conformational Potential Energy Hypersurface (PEHS) of cyclotrisarcosyl was comprehensively investigated at the DFT (B3LYP/6-31G(d), B3LYP/6-31G(d,p) and B3LYP/6-311++G(d,p)), levels of theory. The equilibrium structures, their relative stability, and the Transition State (TS) structures involved in the conformational interconversion pathways were analyzed. Aug-cc-pVTZ//B3LYP/6-311++G(d,p) and MP2/6-31G(d)//B3LYP/6-311++G(d,p) single point calculations predict a symmetric cis-cis-cis crown conformation as the energetically preferred form for this compound, which is in agreement with the experimental data. The conformational interconversion between the global minimum and the twist form requires 20.88 kcal mol-1 at the MP2/6-31G(d)//B3LYP/6-311++G(d,p) level of theory. Our results allow us to form a concise idea about the internal intricacies of the PEHSs of this cyclic tripeptide, describing the conformations as well as the conformational interconversion processes in this hypersurface. In addition, a comparative analysis between the conformational behaviors of cyclotrisarcosyl with that previously reported for cyclotriglycine was carried out     

Multistep conformational interconversion mechanism of cyclododecane. A simple and fast analysis using potential energy curves

An ab initio and Density Functional Theory (DFT) study of the conformational properties of cyclododecane was carried out. The energetically preferred equilibrium structures, their relative stability, and some of the transition state (TS) structures involved in the conformational interconversion pathways were analyzed from RHF/6‐31G(d), B3LYP/6‐31G(d,p) and B3LYP/6311++G(d,p) calculations. Aug‐cc‐pVDZ//B3LYP/6311++G(d,p) single point calculations predict that the multistep conformational interconversion mechanism requires 11.07 kcal/mol, which is in agreement with the available experimental data. These results allow us to form a concise idea about the internal intricacies of the preferred forms of cyclododecane, describing the conformations as well as the conformational interconversion processes in the conformational potential energy hypersurface. Our results indicated that performing an exhaustive analysis of the potential energy curves connecting the most representative conformations is a valid alternate tool to determine the principal conformational interconversion paths for cyclododecane. This methodology represents a satisfactory first approximation for the conformational analysis of medium‐ and large‐size flexible cyclic compounds. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012     

Preconditioned iterative methods for coupled discretizations of fluid flow problems

Computational fluid dynamics, where simulations require largecomputation times, is one of the areas of application of highperformance computing. Schemes such as the SIMPLE (semi-implicitmethod for pressure-linked equations) algorithm are often usedto solve the discrete Navier-Stokes equations. Generally theseschemes take a short time per iteration but require a largenumber of iterations. For simple geometries (or coarser grids)the overall CPU time is small. However, for finer grids or morecomplex geometries the increase in the number of iterationsmay be a drawback and the decoupling of the differential equationsinvolved implies a slow convergence of rotationally dominatedproblems that can be very time consuming for realistic applications.So we analyze here another approach, DIRECTO, that solves theequations in a coupled way. With recent advances in hardwaretechnology and software design, it became possible to solvecoupled Navier-Stokes systems, which are more robust but implyincreasing computational requirements (both in terms of memoryand CPU time). Two approaches are described here (band blockLU factorization and preconditioned GMRES) for the linear solverrequired by the DIRECTO algorithm that solves the fluid flowequations as a coupled system. Comparisons of the effectivenessof incomplete factorization preconditioners applied to the GMRES(generalized minimum residual) method are shown. Some numericalresults are presented showing that it is possible to minimizeconsiderably the CPU time of the coupled approach so that itcan be faster than the decoupled one.     

Binding mechanism of RGD and its mimetics to receptor GPIIb/IIIa. A theoretical study

In order to better understand, at a sub-molecular level, the minimal structural requirements for the recognition process in the platelet aggregation inhibitory activity, a series of RGD mimetics were examined as fibrinogen receptor antagonists variants. We simulate the electronic interactions between RGD with its biological receptor in terms of smaller molecules. MeCOO⁻ was used to mimic the side chain of deprotonated Asp and Meguanidinium group mimicked the side chain of the protonated Arg. Alternative moieties present on the RGD mimetics were also studied in this report. AM1; RHF/3-21G; B3LYP/6-31++G^** in the gas phase. Also, B3LYP/6-31++G^** calculations using the IPCM solvation model were carried out for all the complexes. Our results indicate that high level of theory calculations and the inclusion of solvent effects are crucial in order to obtain satisfactory of accuracy in the electronic distributions of these compounds.     

An analytic ring closure condition for geometrical algorithm to search the conformational space

The recently reported geometrical algorithm to search the conformational space (GASCOS) scans conformational space exhaustively using an internal coordinate tree search. Using only geometrical operations and a set of criteria for eliminating chemically unreasonable atomic arrangements, the algorithm generates starting geometries for optimizations by molecular mechanics or by molecular orbital procedures. Up until now GASCOS has been used for linear structures, but an extension to cyclic structures is reported here.     

A potentiometric and spectrophotometric study on acid-base equilibria in ethanol-aqueous solution of acetazolamide and related compounds

Acid-base equilibria in ethanol-aqueous solution of 5-acetamido-1,3,4-thiadiazole-2-sulfonamide (acetazolamide, H(2)acm), 5-tertbutyloxycarbonylamido-1,3,4-thiadiazole-2-sulfonamide (B-H(2)ats), 5-amino-1,3,4-thiadiazole-2-sulfonamide (Hats) and 5-amino-1,3,4-thiadiazole-2-thiol (Hatm) at 25 degrees C, 0.15 mol dm(-3) ionic strength (NaNO(3)), have been investigated by potentiometry and UV spectrophotometry. The ionization constants were calculated with SUPERQUAD program from potentiometric measurements and by a method according to Edsall et al. using the mole fractions determined by complementary tri-stimulus colorimetry (CTS). The constants obtained by potentiometry were: B-H(2)ats, pk(a(1))=7.33(3) and pk(a(2))=9.27(1); Hats, pk(a(1))=2.51(3) and pk(a(2))=8.49(1); Hatm, pk(a(1))=1.92(1) and pk(a(2))=6.81(1); whereas the constants determined by spectrophotometry were: H(2)acm, pk(a(1))=7.78(1) and pk(a(2))=9.57(2); B-H(2)ats, pk(a(1))=7.71(2) and pk(a(2))=9.61(2); Hats, pk(a(1))=2.19(3) and pk(a(2))=8.61(2); Hatm, pk(a(2))=6.90(2). Theoretical calculations using MO semiempirical and ab-initio RHF/6-31G* computations for the compounds were also performed. It was possible to clarify the preferred deprotonation mechanism of acetazolamide and B-H(2)ats in which the first deprotonation takes place at the carbonamido group.