Liquid Mixtures Involving Hydrogenated and Fluorinated Alcohols: Thermodynamics, Spectroscopy, and Simulation

This article reports a combined thermodynamic, spectroscopic, and computational study on the interactions and structure of binary mixtures of hydrogenated and fluorinated substances that simultaneously interact through strong hydrogen bonding. Four binary mixtures of hydrogenated and fluorinated alcohols have been studied, namely, (ethanol + 2,2,2-trifluoroethanol (TFE)), (ethanol + 2,2,3,3,4,4,4-heptafluoro-1-butanol), (1-butanol (BuOH) + TFE), and (BuOH + 2,2,3,3,4,4,4-heptafluoro-1-butanol). Excess molar volumes and vibrational spectra of all four binary mixtures have been measured as a function of composition at 298 K, and molecular dynamics simulations have been performed. The systems display a complex behavior when compared with mixtures of hydrogenated alcohols and mixtures of alkanes and perfluoroalkanes. The combined analysis of the results from different approaches indicates that this results from a balance between preferential hydrogen bonding between the hydrogenated and fluorinated alcohols and the unfavorable dispersion forces between the hydrogenated and fluorinated chains. As the chain length increases, the contribution of dispersion increases and overcomes the contribution of H-bonds. In terms of the liquid structure, the simulations suggest the possibility of segregation between the hydrogenated and fluorinated segments, a hypothesis corroborated by the spectroscopic results. Furthermore, a quantitative analysis of the infrared spectra reveals that the presence of fluorinated groups induces conformational changes in the hydrogenated chains from the usually preferred all-trans to more globular arrangements involving gauche conformations. Conformational rearrangements at the CCOH dihedral angle upon mixing are also disclosed by the spectra.

Síntese de biguanidas e avaliação da sua atividade biológica em linhas de células tumorais

As biguanidas são um grupo de compostos com diversas atividades biológicas. Recentemente, esta família de compostos tem sido estudada não só pela sua atividade hipoglicemiante, mas também pela sua atividade anti-proliferativa. Um dos objetivos deste estudo foi a síntese de biguanidas, com cadeias laterais com diferentes estruturas e grupos funcionais. O trabalho desenvolvido permitiu a síntese de diversas biguanidas, tendo sido isolados quatro compostos. Outro dos objetivos deste estudo foi avaliar a atividade anti-proliferativa de biguanidas, na linha celular MDST8. Para esse efeito, foi desenvolvido inicialmente um método de quantificação celular com base na atividade ATPásica, testado nas linhas celulares MDST8, MCF7 e BRIN-BD11, tendo sido utilizado como referência a quantificação pelo método das desidrogenases. Os compostos estudados com melhor atividade anti-proliferativa apresentaram IC50 da ordem de 2,5 – 2,9 x10-3 M. Estes valores foram observados em biguanidas cujos grupos substituintes possuíam cadeias hidrocarbonadas cíclicas, alifáticas ou aromáticas p-substituídas, na sua estrutura; Abstract: Synthesis of biguanides and evaluation of their biologic activity in tumor cell lines Biguanides are a group of compounds which have diverse biological activities. Recently, this family of compounds has been studied not only for its hypoglycemic activity, but also for its anti-proliferative activity. One purpose of this study was the synthesis of biguanides, with side chains with different structures and functional groups. The work led to the synthesis of several biguanides, with the isolation of four compounds. Another objective of this study was the evaluation of the anti-proliferative activity of biguanides, in the cell line MDST8. To this aim, it was initially developed a cell quantification method based on the ATPase activity, tested in MDST8, MCF7 and BRIN-BD11 cell lines, with the dehydrogenases method used as reference. The studied compounds with better anti-proliferative activity had IC50 in the range from 2.5 to 2.9 x10-3 M for biguanides whose substituent groups had cyclic hydrocarbon, aliphatic or p-substituted aromatic chains in their structure.

DFT STUDIES ON THE MECHANISM OF RING-OPENING POLYMERIZATION OF LACTIDE WITH ADENINE

The use of organic molecules as catalysts for the ring-opening polymerization (ROP) of cyclic esters has gained much interest last years.[1] The use of a molecule of biological interest, able to initiate ROP of cyclic esters without any cocatalyst is even more interesting, as the resulting material will not contain any catalytic residue. Nucleobase-polymer conjugates development is thus an emerging area envisaging biomedical applications.[2] However, they are usually synthesized by tedious multistep procedures. Recently, adenine was used as organoinitiator for the ROP of L-lactide.[3] Reaction conditions involving short reaction times and relatively low temperatures enable the access to adenine-polylactide(Adn-PLA)conjugates in a simple one-step procedure, without additional catalyst and in the absence of solvent. In this study, computational investigations with density functional theory (DFT) were performed in order to clarify the reaction mechanism leading to the desired Adn-PLA. The results show that a hydrogen bond catalytic mechanism, involving a nucleophilic attack of the activated amine group of adenine onto the carbonyl group of lactide, seem to be plausible.