The nature of binding between bovine serum albumin (BSA) and the antidepressant tianeptine and a new series of esters derivatives were studied in this paper. The interactions with BSA were investigated by UV-Vis and fluorescence spectroscopy at three different temperatures. The fluorescence quenching experiments showed that BSA interactions with tianeptine could be dynamic while to its esters a static mechanism was observed. The results showed that tianeptine quenches the intrinsic fluorescence of BSA more efficiently than its esters due to the presence of the free acid portion. The number of binding sites determined by fluorescence spectroscopy is approximately equal to 1 indicating that there is one binding site between BSA tianeptine esters, but the presence of a second interaction site for tianeptine at higher temperatures could be not ruled out. Molecular docking calculations point out a strong affinity of tianeptine and its esters to the site IIA of protein, supporting the hypothesis of a static quenching mechanism.

In this work, semi-empirical AM1 and DFT B3LYP/6-31G** calculations were applied in the study of the interconversion among tautomers of several naphthazarin and 5-amino-8-hydroxy-1,4-naphthoquinone β-substituted derivatives bearing electron-donor or electron-withdrawing groups. Using a semi-empirical method, detailed potential energy landscapes for proton transfers were built, from which four tautomers and four transition states of interconversions were identified for each compound. These structures were recalculated without restraints and, using the Boltzmann distribution, the populations for each of the four tautomers and their respective molar fractions were calculated. The calculations showed that the tautomeric equilibrium is shifted to the tautomer where the ring with the substituent has a quinonic nature and is more pronounced when the β-substituent is an electron donor group. For derivatives of 5-amino-8-hydroxy-1,4-naphthoquinone, an equilibrium between an aromatic and a 1,5-naphthoquinonic non-aromatic enamine was observed, being the former the most stable.

In this work we carried out a study covering conformational analysis, docking calculations and molecular dynamics (MD) simulations of six excited state intramolecular proton transfer (ESIPT)-fluorescent 2-(2'-hydroxyphenyl)-benzoxazoles, interacting with the Dickerson-Drew (d(CGCGAATTCGCG)2) dodecamer in B-DNA conformation. In the analysis of the molecular docking calculations, the derivatives with the -NH2 group in the phenolic ring presented the most favorable interaction energies with the DNA, and the scores were even more favorable for the ligands containing the -NO2 group as substituent in the benzoxazolic ring. In the analysis of the MD simulations, the complexes showed stable interactions, with minimal induced structural distortions in the DNA, being the largest increase of the Rise parameter when the ligands were intercalated, and also the unwinding of Twist. During all simulations, the ligands showed stable interactions with the oligonucleotide, without denaturation. Considering these interactions and the peculiar photophysical properties of this class of molecules, they could be used as biological probes.

In this work we present a simple model for the kinetics of agglomeration and aggregation of colloidal particles. We consider that particles agglomerate rapidly and endothermically forming oligomers. These oligomers can, in turn, aggregate irreversibly, in a process that leads to the destabilization of the colloidal system. As these two processes have very different relative energy activations, they occur in different time-scales: the first step is faster and reaches a state of quasi‑equilibrium. Because of this, the enthalpy change during the agglomeration can be experimentally determined through the variable temperature multiple light scattering (VTMLS) method. Interestingly, this value is related to the relative kinetic stability of the system and can be used to evaluate the stability of new colloidal compositions. Our results are in qualitative agreement with experimental data of low concentration colloidal dispersions consisted of polymer particles and/or surfactant-coated particles.

Bases de Tröger são moléculas que, devido à sua geometria, ligam-se de modo enantiosseletivo ao DNA. Usando dinâmica molecular, foram simuladas bases de Tröger com substituintes proflavina e fenantrolina. Partindo das bases docadas no DNA, foram investigadas as distorções induzidas em dois modos de ligação: intercalação e ligação de sulco. Nos complexos de intercalação as bases apresentam tempo de residência elevado e distorcem a dupla hélice levando a um desenrolamento parcial e a valores não-canônicos de alguns ângulos torcionais. Nos complexos de ligação de sulco, elas exibem alta mobilidade e levam a uma alteração no modo de ligação, interagindo com o sulco via ponte diazocina. Os resultados sugerem a intercalação de um substituinte, com contatos adicionais no sulco, como o modo de ligação preferencial destas bases de Tröger, sendo que a ligação de sulco explica a fraca ligação dos isômeros dextrorrotatórios.

Tröger bases are a class of molecules that, due to its geometry, bind enantioselectively to DNA. Molecular dynamic simulations were performed with levorotatory isomers of proflavine and phenanthroline substituted Tröger bases. Starting with the bases docked in DNA, the distortions they promote in the double helix were investigated in two possible modes: intercalation and minor groove binding. In the intercalation complexes, they presented long residence times and distorted the double helix leading to partial unwinding and to non-canonical values of some backbone angles. In the minor groove complexes, they displayed high mobility, leading to a change in the binding mode, interacting with the minor groove mainly through the diazocin bridge. The results suggested the intercalation of one substituent (with additional contacts in the minor groove) as the preferential binding mode for these Tröger bases, while minor groove binding may explain the weaker binding observed for the dextrorotatory isomers.

A modificação experimental para a síntese do MESG (2-amino-6-mercapto-7-metilpurina ribonucleosídeo) 1 foi realizada com sucesso e sua caracterização total apresentada. ESI(+)-MSMS em alta resolução foram realizados indicando que a clivagem nucleosídica como principal e um possível mecanismo S N1. Cálculos ab initio baseados em estados de transição blueprint corroboram com a proposta de um mecanismo S N1 e descartam a possibilidade de um mecanismo S N2. Ensaios com a enzima purina nucleosídica fosforilase (PNP, tanto humana como de M. tuberculosis) indicam a eficiência do substrato na reação de fosforilação do MESG e permitem a determinação de fosfato inorgânico em tempo real em ensaios biológicos.

A modified experimental procedure for the synthesis of MESG (2-amino-6-mercapto-7-methylpurine ribonucleoside) 1 has been successfully performed and its full characterization is presented. High resolution ESI(+)-MSMS indicates both the nucleoside bond cleavage as the main fragmentation in the gas phase and a possible S N1 mechanism. Ab initio transition state calculations based on the blue print transition state support this mechanistic rationale and discard an alternative S N2 mechanism. Assays using purine nucleoside phosphorylase (PNP) enzyme (human and M. tuberculosis sources) indicate its efficiency in the phosphorolysis of MESG and allow the quantitative determination of inorganic phosphate in real time assay.