Dissociation Mode of the O-H Bond in Betanidin, pKa-Clusterization Prediction, and Molecular Interactions via Shape Theory and DFT Methods.

Betanidin (Bd) is a nitrogenous metabolite with significant bioactive potential influenced by pH. Its free radical scavenging activity and deprotonation pathway are crucial to studying its physicochemical properties. Motivated by the published discrepancies about the best deprotonation routes in Bd, this work explores all possible pathways for proton extractions on that molecule, by using the direct approach method based on pKa. The complete space of exploration is supported by a linear relation with constant slope, where the pKa is written in terms of the associated deprotonated molecule energy. The deprotonation rounds 1, …, 6 define groups of parallel linear models with constant slope. The intercepts of the models just depend on the protonated energy for each round, and then the pKa can be trivially ordered and explained by the energy. We use the direct approximation method to obtain the value of pKa. We predict all possible outcomes based on a linear model of the energy and some related verified assumptions. We also include a new measure of similarity or dissimilarity between the protonated and deprotonated molecules, via a geometric-chemical descriptor called the Riemann-Mulliken distance (RMD). The RMD considers the cartesian coordinates of the atoms, the atomic mass, and the Mulliken charges. After exploring the complete set of permutations, we show that the successive deprotonation process does not inherit the local energy minimum and that the commutativity of the paths does not hold either. The resulting clusterization of pKa can be explained by the local acid and basic groups of the BD, and the successive deprotonation can be predicted by using the chemical explained linear models, which can avoid unnecessary optimizations. Another part of the research uses our own algorithm based on shape theory to determine the protein's active site automatically, and molecular dynamics confirmed the results of the molecular docking of Bd in protonated and anionic form with the enzyme aldose reductase (AR). Also, we calculate the descriptors associated with the SET and SPLET mechanisms.

Shape Theory Applied to Molecular Docking and Automatic Localization of Ligand Binding Pockets in Large Proteins.

Automatic search of cavities and binding mode analysis between a ligand and a 3D protein receptor are challenging problems in drug design or repositioning. We propose a solution based on a shape theory theorem for an invariant coupled system of ligand-protein. The theorem provides a matrix representation with the exact formulas to be implemented in an algorithm. The method involves the following results: (1) exact formulae for the shape coordinates of a located-rotated invariant coupled system; (2) a parameterized search based on a suitable domain of van der Waals radii; (3) a scoring function for the discrimination of sites by measuring the distance between two invariant coupled systems including the atomic mass; (4) a matrix representation of the Lennard-Jones potential type 6-12 and 6-10 as the punctuation function of the algorithm for a molecular docking; and (5) the optimal molecular docking as a solution of an optimization problem based on the exploration of an exhaustive set of rotations. We apply the method in the xanthine oxidase protein with the following ligands: hypoxanthine, febuxostat, and chlorogenic acid. The results show automatic cavity detection and molecular docking not assisted by experts with meaningful amino acid interactions. The method finds better affinities than the expert software for known published cavities.

Mechanism of Antioxidant Activity of Betanin, Betanidin and Respective C15-Epimers via Shape Theory, Molecular Dynamics, Density Functional Theory and Infrared Spectroscopy.

Betanin and betanidin are compounds with extensive interest; they are effectively free radical scavengers. The present work aims to elucidate the differences between the mechanism of the antioxidant activity of betanin, betanidin, and their respective C15-epimers. Shape Theory establishes comparisons between the molecules' geometries and determines parallelisms with the descriptors BDE, PA, ETE IP, PDE, and infrared spectra (IR) obtained from the molecule simulations. Furthermore, the molecules were optimized using the B3LYP/6-31+G(d,p) protocol. Finally, the molecular docking technique analyzes the antioxidant activity of the compounds in the complex with the therapeutic target xanthine oxidase (XO), based on a new proposal for the geometrical arrangement of the ligand atoms in the framework of Shape Theory. The results obtained indicate that the SPLET mechanism is the most favorable in all the molecules studied and that the first group that loses the hydrogen atom in the four molecules is the C17COOH, presenting less PA the isobetanidin. Furthermore, regarding the molecular docking, the interactions of these compounds with the target were favorable, standing out to a greater extent the interactions of isobetanidin with XO, which were analyzed after applying molecular dynamics.

Sulfur-based redox reactions in Mo3S7(4+) and Mo3S4(4+) clusters bearing halide and 1,2-dithiolene ligands: a mass spectrometric and density functional theory study.

The gas phase fragmentation reactions of sulfur-rich [Mo(3)S(7)Br(6)](2-) (1(2-)), [Mo(3)S(7)(bdt)(3)](2-) (2(2-)), and [Mo(3)S(4)(bdt)(3)](2-) (3(2-)) (bdt = benzenedithiolate) complexes have been investigated by electrospray ionization (ESI) tandem mass spectrometry and theoretical calculations at the density functional theory level. Upon collision induced dissociation (CID) conditions, the brominated 1(2-) dianion dissociates through two sequential steps that involves a heterolytic Mo-Br cleavage to give [Mo(3)S(7)Br(5)](-) plus Br(-) followed by a two-electron redox process that affords [Mo(3)S(5)Br(5)](-) and diatomic S(2) sulfur. Dianion [Mo(3)S(7)(bdt)(3)](2-) (2(2-)) dissociates through two sequential redox processes evolving diatomic S(2) sulfur and neutral bdt to yield [Mo(3)S(5)(bdt)(3)](2-) and [Mo(3)S(5)(bdt)(2)](2-), respectively. Conversely, dianion [Mo(3)S(4)(bdt)(3)](2-) (3(2-)), with sulfide instead of disulfide S(2)(2-) bridged ligands, remains intact under identical fragmentation conditions, thus highlighting the importance of disulfide ligands (S(2)(2-)) as electron reservoirs to trigger redox reactions. Regioselective incorporation of (34)S and Se at the equatorial position of the Mo(3)S(7) cluster core in 1(2-) and 2(2-) have been used to identify the product ions along the fragmentation pathways. Reaction mechanisms for the gas-phase dissociation pathways have been elucidated by means of B3LYP calculations, and a comparison with the solution reactivity of Mo(3)S(7) and Mo(3)S(4) clusters as well as closely related Mo/S/dithiolene systems is also discussed.

A density functional theory study of the magnetic exchange coupling in dinuclear manganese(II) inverse crown structures.

The magnetic exchange coupling constants between two Mn(II) centers for a set of five inverse crown structures have been investigated by means of a methodology based on broken-symmetry unrestricted density functional theory. These novel and highly unstable compounds present superexchange interactions between two Mn centers, each one with S = 5/2 through anionic "guests" such as oxygen, benzene, or hydrides or through the cationic ring formed by amide ligands and alkali metals (Na, Li). Magnetic exchange couplings calculated at B3LYP/6-31G(d,p) level yield strong antiferromagnetic couplings for compounds linked via an oxygen atom or hydride and very small antiferromagnetic couplings for those linked via a benzene molecule, deprotonated in either 1,4- or 1,3- positions. Analysis of the magnetic orbitals and spin polarization maps provide an understanding of the exchange mechanism between the Mn centers. The dependence of J with respect to 10 different density functional theory potentials employed and the basis set has been analyzed.

Calorimetric and computational study of 3-buten-1-ol and 3-butyn-1-ol. Estimation of the enthalpies of formation of 1-alkenols and 1-alkynols.

The enthalpies of combustion and vaporization of 3-buten-1-ol and 3-butyn-1-ol have been measured by static bomb combustion calorimetry and correlation gas chromatography techniques, respectively, and the gas-phase enthalpies of formation, Delta(f)H degrees (m)(g), have been determined, the values being -147.3 +/- 1.8 and 16.7 +/- 1.6 kJ mol(-1), for 3-buten-1-ol and 3-butyn-1-ol, respectively. High level calculations at the G2 and G3 levels have also been carried out. Relationships between the enthalpies of formation of 1-alkanols, 1-alkenols and 1-alkynols and with the corresponding hydrocarbons have been discussed. From the calculated contributions to Delta(f)H degrees (m)(g) for the substitutions of CH(3) by CH(2)OH, CH(3)CH(2) by CH(2)=CH and CH(3)CH(2) by CH triple bond C, we have estimated the Delta(f)H degrees (m)(g) values for 3-buten-1-ol and 3-butyn-1-ol, in excellent agreement with the experimental ones. Delta(f)H degrees (m)(g) values for 1-alkenols and 1-alkynols up to 10 carbon atoms have also been estimated.