Photophysical Deactivation Mechanisms of the Pyrimidine Analogue 1-Cyclohexyluracil

The photophysical relaxation mechanisms of 1-cyclohexyluracil, in vacuum and water, were investigated by employing the Multi-State CASPT2 (MS-CASPT2, Multi-State Complete Active-Space Second-Order Perturbation Theory) quantum chemical method and Dunning’s cc-pVDZ basis sets. In both environments, our results suggest that the primary photophysical event is the population of the S11(ππ*) bright state. Afterwards, two likely deactivation pathways can take place, which is sustained by linear interpolation in internal coordinates defined via Z-Matrix scans connecting the most important characteristic points. The first one (Route 1) is the same relaxation mechanism observed for uracil, its canonical analogue, i.e., internal conversion to the ground state through an ethylenic-like conical intersection. The other route (Route 2) is the direct population transfer from the S11(ππ*) bright state to the T23(nπ*) triplet state via an intersystem crossing process involving the (S11(ππ*)/T23(nπ*))STCP singlet-triplet crossing point. As the spin-orbit coupling is not too large in either environment, we propose that most of the electronic population initially on the S11(ππ*) state returns to the ground following the same ultrafast deactivation mechanism observed in uracil (Route 1), while a smaller percentage goes to the triplet manifold. The presence of a minimum on the S11(ππ*) potential energy hypersurface in water can help to understand why experimentally it is noticed suppression of the triplet states population in polar protic solvent.

Computational Study of the C-H∙∙∙H-C Contacts in Valine-Methane Complexes.

<div> <p>A series of complexes between neutral Valine and methane that feature potential homopolar C-H∙∙∙H-C contacts were located on the MP2/aug-cc-pVTZ potential energy hypersurface. In order to better estimate the strength of this contacts, the interaction energies were improve by single-point calculations at different levels of theory (MP2, CCSD(T), SAPT2, SAPT2+3) together with Dunning’s basis sets (aug-cc-pVXZ; X=T,Q,5). Topological analysis of the electron density within the QTAIM framework, NCI plots and energy decomposition within the SAPT framework were used to discuss the nature of this interactions. The complexes whose monomers only interact though C-H∙∙∙H-C contacts indicate that these interactions are entirely due to dispersion forces, are not directional and are much stronger than expected (the interaction energies of the complexes range from -0.7 to -1.0 kcal/mol). This large value is remarkable considering the small size of the interacting groups herein considered (methane, and one or two Valine’s methyl groups), and indicates that in biological systems, where those interactions can be very numerous in the presence of multiple aliphatic amino acids, if those interactions are not properly model, magnitudes as ligand-receptor affinities, protein-protein interaction energies and protein stabilities might be grossly misestimated. Finally, since some of the computed complexes also include stronger interactions than homopolar C-H∙∙∙H-C contacts, we analyzed if the potential C-H∙∙∙H-C contacts in these complexes are really contributing to stabilize the complexes or are just a geometrical artifact arising from the maximization of stronger interactions.</p> </div>

Computational Study of the C-H∙∙∙H-C Contacts in Valine-Methane Complexes.

<div> <p>A series of complexes between neutral Valine and methane that feature potential homopolar C-H∙∙∙H-C contacts were located on the MP2/aug-cc-pVTZ potential energy hypersurface. In order to better estimate the strength of this contacts, the interaction energies were improve by single-point calculations at different levels of theory (MP2, CCSD(T), SAPT2, SAPT2+3) together with Dunning’s basis sets (aug-cc-pVXZ; X=T,Q,5). Topological analysis of the electron density within the QTAIM framework, NCI plots and energy decomposition within the SAPT framework were used to discuss the nature of this interactions. The complexes whose monomers only interact though C-H∙∙∙H-C contacts indicate that these interactions are entirely due to dispersion forces, are not directional and are much stronger than expected (the interaction energies of the complexes range from -0.7 to -1.0 kcal/mol). This large value is remarkable considering the small size of the interacting groups herein considered (methane, and one or two Valine’s methyl groups), and indicates that in biological systems, where those interactions can be very numerous in the presence of multiple aliphatic amino acids, if those interactions are not properly model, magnitudes as ligand-receptor affinities, protein-protein interaction energies and protein stabilities might be grossly misestimated. Finally, since some of the computed complexes also include stronger interactions than homopolar C-H∙∙∙H-C contacts, we analyzed if the potential C-H∙∙∙H-C contacts in these complexes are really contributing to stabilize the complexes or are just a geometrical artifact arising from the maximization of stronger interactions.</p> </div>

A prelude to building mathematical models for polypeptide folding: analysis on the conformational potential energy hypersurface cross-sections of N-acetyl-glycyl-glycine-N′-methylamide

Finding a relationship on how a three-dimensional protein folds from its linear amino acid chain gets more complex with increasing chain length, so working on a smaller peptide conformational problem can provide initial ideas on what are the main molecular forces and how these influence the folding process. Following the study of conformations of amino acid units entering the proteins to understand the secondary structure of small peptides, this paper proposes mathematical models for the several two-rotor cross-sections of the five-dimensional N-acetyl-glycyl-glycine-N′-methylamide potential energy hypersurface (PEHS). These cross-sections are extracted along the first glycine subunit, with its coordinates fixed at the five energy minima of the glycine diamide. The resulting mathematical models yield an average RMSE of 1.36 kJ mol−1 and an average R2 of 0.9923 with respect to energy values obtained from DFT calculations. The minima geometries obtained from these models are also in good agreement with DFT-optimized energy minima conformers. An important aspect of this study also tackles the relationship between the PEHS of the glycyl-glycine diamide and its glycine subunits. It has been observed that there are deviations up to 28.35 kJ mol−1 and 29.52 kJ mol−1 between the PEHS cross-sections along γL and γD conformations, respectively, in the first glycine subunit. This may suggest that there are significant backbone–backbone intermolecular forces acting on the dipeptide. The abovementioned findings can help in developing more complex mathematical models for polypeptide folding from amino acid subunits.

Fitting Potential Energy Hypersurfaces

Molecular dynamics (MD) and Monte Carlo (MC) simulations are the two most powerful methods for the investigation of dynamic behavior of atomic and molecular motions of complex systems. To date, such studies have been used to investigate chemical reaction mechanisms, energy transfer pathways, reaction rates, and product yields in a wide array of polyatomic systems. In addition, MD/MC methods have been successfully applied for the investigation of gas-surface reactions, diffusion on surfaces and in the bulk, membrane transport, and synthesis of diamond using chemical vapor deposition (CVD) techniques. The structure of vapor deposited rare gas matrices has been studied using trajectories procedures. If the chemical reaction of interest contains three atoms or fewer, various types of quantum and semiclassical calculations can be brought to bear on the problem. These methods include wave packet studies, close-coupling calculations at various levels of accuracy, and S-matrix theory. Several excellent review articles have been published describing the principal techniques and problems involved in conducting MD studies; the reader may wish to consult these as background material for this discussion. With the advent of relatively inexpensive, powerful personal computers, MD/MC simulations have become routine. Once the potential-energy hypersurface for the system has been obtained, the computations are straightforward, though time-consuming. In the majority of cases, the computational time required is on the order of hours to a few days. However, the accuracy of these simulations depends critically on the accuracy of the potential hypersurface used. The major problem associated with MD/MC investigations is the development of a potential-energy hypersurface whose topographical features are sufficiently close to those of the true, but unknown, surface that the results of the calculations are experimentally meaningful. Once the potential surface is chosen or computed, all the results from any quantum mechanical, semiclassical, or classical scattering or equilibrium calculation are determined. The only purpose of the MD calculations is to ascertain what these results are. Therefore, the most critical part of any MD/MC study is the development of the potential-energy hypersurface and the associated force field.

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