Catalina Soriano-Correa

Insight into the informational-structure behavior of the Diels-Alder reaction of cyclopentadiene and maleic anhydride

The course of the Diels-Alder reactions of cyclopentadiene and maleic anhydride were studied. Two reaction paths were modelled: endo- and exo-selective paths. All structures within the transient region were characterized and analyzed by means of geometrical descriptors, physicochemical parameters and information-theoretical measures in order to observe the linkage between chemical behavior and the carriage of information. We have shown that the information-theoretical characterization of the chemical course of the reaction is in complete agreement with its phenomenological behavior in passing from reactants to products. In addition, we were able to detect the main differences between the two reaction mechanisms. This type of informational analysis serves to provide tools to help understand the chemical reactivity of the two simplest Diels-Alder reactions, which permits the establishment of a connection between the quantum changes that molecular systems exert along reaction coordinates and standard physicochemical phenomenology. In the present study, we have shown that every reaction stage has a family of subsequent structures that are characterized not solely by their phenomenological behavior but also by informational properties of their electronic density distribution (localizability, order, uniformity). Moreover, we were able to describe the main differences between endo-adduct and exo-adduct pathways. With the advent of new experimental techniques, it is in principle possible to observe the structural changes in the transient regions of chemical reactions. Indeed, through this work we have provided the theoretical concepts needed to unveil the concurrent processes associated with chemical reactions.

Electronic structure evaluation through quantum chemical descriptors of 17β-aminoestrogens with an anticoagulant effect.

17β-aminoestrogens have been experimentally studied due to their anticoagulant effect, shown both in in vitro and in vivo assays; this is a non-typical behavior for steroids. The anticoagulant effect of these aminoestrogens has been related to the aromaticity of the A-ring of the steroid molecule; as well as to the length of the amino-alcohol side-chain at C17, which might have an influence on the biological activity of these compounds. The study of the electronic structure of 17β-aminoestrogens using quantum chemical descriptors could provide significant information and may contribute to a better understanding of structure-activity relationships in these molecules. In this work, we present a density functional theory (DFT) study at the B3LYP level of theory for selected 17β-aminoestrogens compounds, with the main purpose of characterizing their electronic and physicochemical properties and relating them to their anticoagulant effect, using quantum chemical descriptors such as: atomic charges, bond order, electrostatic potential isosurface analysis, hardness, electrophilicity and aromaticity indexes. The results obtained from these quantum chemical descriptors, led us to characterize the physicochemical properties, reactive sites and substituent influence on electronic structure, as well as to identify additional quantum chemical descriptors that could be associated with the anticoagulant effect of 17β-aminoestrogens.

Theoretical Study of the Competition between Intramolecular Hydrogen Bonds and Solvation in the Cys-Asn-Ser Tripeptide

A study of the competition between intra- and intermolecular hydrogen bonds and its influence on the stability of the Cys-Asn-Ser tripeptide in aqueous solution was performed by using the averaged solvent electrostatic potential from molecular dynamics method (ASEP/MD). The model combines a DFT-B3LYP/6-311+G(d) quantum treatment in the description of the solute molecule with NVT molecular dynamics simulations in the description of the solvent. In gas phase, the most stable structure adopts a C5 conformation. Somewhat higher in energy are found the PP(II) and C7eq structures. In solution, the stability order of the different conformers is reversed: the PP(II) structure becomes the most stable, and the C5 structure is strongly destabilized. The conformational equilibrium is shifted toward conformations in which the intramolecular hydrogen bonds (IHB) have been substituted with intermolecular hydrogen bonds with the water molecules. The solvent stabilizes extended structures without IHBs that are not stable in vacuum. The effect of the protonation state on the conformational equilibrium was also analyzed.

The Cys-Asn-Ser carboxyl-terminal end group is the pharmacophore of the amebic anti-inflammatory monocyte locomotion inhibitory factor (MLIF)

The monocyte locomotion inhibitory factor (MLIF) is an anti-inflammatory oligopeptide produced by Entamoeba histolytica. Among its different effects, it inhibits locomotion of human monocytes, hence its original name. Previous experimental studies have shown that the anti-inflammatory properties of MLIF (Met-Gln-Cys-Asn-Ser) remained when aminoacid glutamine was substituted by a proline in the second position (pMLIF: Met-Pro-Cys-Asn-Ser). By changing the order of MLIF amino acids, the resulting scrambled oligopeptide (sMLIF: Gln-Cys-Met-Ser-Asn) has failed activity. By means of ab initio study at the Hartree-Fock and Density Functional Theory levels, it was found that MLIF and pMLIF peptides maintain a great structural similarity among the last three amino acids (...Cys-Asn-Ser) predicting a pharmacophore. The objective of this work was to experimentally verify in vivo and in vitro the existence of the pharmacophore group in MLIF. We assayed three tripeptides by respiratory burst and delayed hypersensitivity skin reactions. The tripeptide Cys-Asn-Ser carboxyl-terminal end group maintained 100% of its biological properties, as well as the anti-inflammatory activity of MLIF, while the other tripeptides tested did not do that.

Oxidation mechanism of methionine by HO• radical: a theoretical study.

A theoretical investigation at the MP2/6-311++G(2d,2p)//MP2/6-31+G(d,p) level was employed in order to study the one-electron oxidation mechanism of methionine in aqueous solution. Three reaction paths corresponding to the HO(•), O(2) attack and hydrolysis were considered. Results show that all the processes are exothermic and that the rate determining step can be associated with the hydrolysis reaction. DFT computations with different exchange-correlation potentials were performed in order to verify their reliability in the description of the cyclic adduct produced in the HO(•) attack step.

Theoretic-information entropies analysis of nanostructures: ab initio study of PAMAM precursors and dendrimers G0 to G3

Information theory in conjugated and in Hilbert spaces is employed to analyse the growing behaviour of nanostructures. Shannon entropies in position and momentum spaces require costly and time-consuming computations as the size of the molecules increases in contrast with information entropies in Hilbert space, which are shown to be highly advantageous for analysing large molecules. In this work, ab initio electronic structure calculations at the Hartree–Fock (HF), MP2 and B3LYP levels of theory were performed to analyse the initial steps towards growing nanostructured molecules of polyamidoamine (PAMAM) dendrimers, starting from the monomers, dimers, trimers and tetramers up to generations G0 (with 84 atoms), G1 (228 atoms), G2 (516 atoms) and G3 (1092 atoms). This was achieved by using selected physical descriptors such as the radius of gyration, the asphericity factor, the moments of inertia, the dipole moments, the total energies and chemical reactivity indices such as the hardness, softness and the electrophilicity index at the HF/3-21G* level of theory. For the chemical indices, higher level calculations at the B3LYP/6-311++ G** and MP2/6-311+ G* levels were also performed in order to account for the effects of electron correlation. Information-theoretic measures of the Shannon type in conjugated space were employed to characterise the G0–PAMAM precursors and G0. Hilbert space entropies of the Shannon and Kullback type were employed to provide theoretic-information evidence of the validity of the dense-core model of PAMAM precursors and dendrimers G0 to G3.

Computational study of the electronic structure characterization of a novel anti-inflammatory tripeptide derived from monocyte locomotion inhibitory factor (MLIF)-pentapeptide

The structure and properties of molecules are determined by their charge-density distribution. Several works have shown that electron delocalization along the peptide backbone and side-chain modulates the physical and chemical features of peptides and protein properties. Research on Entamoeba histolytica-soluble factors led to the identification of the pentapeptide Met-Gln-Cys-Asn-Ser, with anti-inflammatory in vivo and in vitro effects. A synthetic pentapeptide, Met-Pro-Cys-Asn-Ser, maintained the same anti-inflammatory actions in experimental assays. A previous theoretical study allowed proposing the Cys-Asn-Ser tripeptide (CNS tripeptide) as the pharmacophore group of both molecules. This theoretical hypothesis was recently confirmed experimentally. The aim of this study was to characterize the electronic structure and physico-chemical properties of the CNS tripeptide through a theoretical study at the second-order Møller-Plesset perturbation theory (MP2) and density functional theory (DFT) theoretical levels. Our results in deprotonation energies show that the hydrogen atom (H2) of the serine-amide group possesses acidic characteristics. This result was confirmed by means of a study of bond order. Atomic charges, dipole moment, frontier molecular orbitals (Highest occupied molecular orbital [HOMO-1] and Lowest unoccupied molecular orbital [LUMO+1]), and electrostatic potential isosurface and its geometric parameters permitted to characterize its electronic structure and physico-chemical features and to identify some reactive sites that could be associated with this tripeptides anti-inflammatory activity.

Predominant Information Quality Scheme for the Essential Amino Acids: An Information‐Theoretical Analysis

In this work we undertake a pioneer information-theoretical analysis of 18 selected amino acids extracted from a natural protein, bacteriorhodopsin (1C3W). The conformational structures of each amino acid are analyzed by use of various quantum chemistry methodologies at high levels of theory: HF, M062X and CISD(Full). The Shannon entropy, Fisher information and disequilibrium are determined to grasp the spatial spreading features of delocalizability, order and uniformity of the optimized structures. These three entropic measures uniquely characterize all amino acids through a predominant information-theoretic quality scheme (PIQS), which gathers all chemical families by means of three major spreading features: delocalization, narrowness and uniformity. This scheme recognizes four major chemical families: aliphatic (delocalized), aromatic (delocalized), electro-attractive (narrowed) and tiny (uniform). All chemical families recognized by the existing energy-based classifications are embraced by this entropic scheme. Finally, novel chemical patterns are shown in the information planes associated with the PIQS entropic measures.

Quantum Information-Theoretical Analyses of Systems and Processes of Chemical and Nanotechnological Interest

The application of information-theoretic concepts and techniques to the study of quantum multielectronic systems is presently attracting the attention of numerous researchers in several fields. This area of inquiry is shedding new light on the conceptual foundations of physics and is also at the core of the new field of Quantum Information Theory, which foresees important technological developments through concepts such as “entanglement”, “teleportation” and “quantum computation”. In line with these developments we present in this Chapter a review of the recent advances performed in our laboratories to study selected molecular processes and mesoscopic systems at the nanoscopic scale by employing information theory concepts to show significant advances of Information Theory applied to chemistry by use of Shannon entropies through the localized/delocalized features of the electron distributions allowing a phenomenological description of the course of elementary chemical reactions by revealing important chemical regions that are not present in the energy profile such as the ones in which bond forming and bond breaking occur. Further, the synchronous reaction mechanism of a SN2 type chemical reaction and the nonsynchronous mechanistic behavior of the simplest hydrogenic abstraction reaction were predicted by use of Shannon entropies analysis. These studies have shown that the information-theoretical measures provide evidence to support the concept of a continuum of transient of Zewail and Polanyi for the transition state rather than a single state, which is also in agreement with other analyses. Although information entropies have been employed in quantum chemistry, applications in large chemical systems are very scarce. For nanostructures, we have been able to show that IT measures can be successfully employed

Computational study of substituent effects on the acidity, toxicity and chemical reactivity of bacteriostatic sulfonamides

Relationships among physicochemical properties, the chemical structure and antibacterial activity of sulfonamides have not been completely explicated yet. Nevertheless, from a therapeutics and prodrugs design point of view, a substituent group can modify the electronic structure, the physicochemical features and chemical reactivity which are critical for the biological activity. In this work, we analyze the substituent effects on the physicochemical properties, toxicity, chemical reactivity and its relation with the bacteriostatic activity of selected sulfonamides by means of DFT-M06-2X calculations in aqueous solution, using quantum chemical and docking descriptors. A correlation between the theoretical acidity and the pKa experimental values has been found. The more active sulfonamides have a larger acidity. The acidity increases with electron-withdrawing substituents. The main reactivity takes place on N4 atoms linked to aromatic ring, and in the SO2NH moiety, which are influenced by substituents. Docking descriptors showed binding affinities between sulfonamides and target receptor, the dihydropteroate synthase (DHPS).