In this work, Density Functional Theory was used in the theoretical study of the coordination of three ligands derived from 8-hydroxyquinoline (8-HQ) with N-acylhydrazone: 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone (INHHQ), 2-[(8-hydroxyquinolinyl)methylene] acetohydrazide (8-H2QH) and 2-[(8-hydroxyquinolinyl)methylene] hydrazinecarboxamide (8-H2QS); with the Zn2+ion. These complexes prevent interactions of the metal ions present in the brain, with the β-amyloid peptide (Aβ), avoiding the formation of aggregates that are responsible for the development of the Alzheimer's disease. The results show that the three ligands coordinate the Zn2+ion in a tridentate form through the O and N atoms of the 8-hydroxyquinoline center and the N of the hydrazonic group, completing the coordination sphere with two chloride ions, creating a bipyramidal structure trigonal, different from the structures of the complexes reported in the literature.

With the increase in life expectancy registered in the past few decades, the prevalence of various medical conditions related to aging has been observed, such as dementia and related neurodegenerative conditions. The number of patients afflicted with these conditions is expected to significantly increase in the coming years. The growing social impact of dementia underlines the need for research aimed at identifying and better understanding this type of condition. Among neurodegenerative diseases, amyloidogenic diseases, in particular Alzheimer's disease (AD), are currently the most common form of dementia. Over the years, several hypotheses have been raised regarding the etiology of AD, such as the cholinergic, glutamatergic, amyloid cascade, oligomeric, metallic and diabetes type 3 hypotheses. Unfortunately, no cure is yet available for this disease, only drugs that aid in controlling the symptoms. This review article conducts a comprehensive approach of the main etiological hypotheses of AD, as well as the treatment prospects associated with each hypothesis.

As pesquisas na área de Química Medicinal têm envolvido diversos aspectos focando o tratamento de doenças tais como câncer, em especial, a combinação de potenciais terapêuticos apresentados por moléculas distintas. Visando isso, realizou-se um estudo computacional combinando a pirazinamida (PZA), um imprescindível tuberculostático com a cisplatina, importante antitumoral, para obter as melhores características de ambas. Foi feita a busca por uma estrutura mais estável para o complexo de estequiometria PZA:platina(II) 2:1 cis-[PtCl2(PZA)2], ou cis-diclorobis(pirazinamido)-platina(II), utilizando para isso a teoria do funcional densidade (DFT) associada ao uso de um planejamento fatorial misto de dois fatores do tipo 5 × 3, para um total de 15 experimentos. Através da avaliação da superfície de resposta e da realização de sete experimentos para validação do modelo, inferiu-se que a estrutura de maior estabilidade refere-se àquela com o diedro 2Cl/1Pt/5O/7C sob um ângulo de 18,9°.

Research in Medicinal Chemistry has involved numerous aspects focusing on the treatment of several kinds of diseases, such as cancer, especially by the combination of therapeutic potentials by using different molecules. With this aim, a computational study combining pyrazinamide (PZA), an indispensable tuberculostatic drug, and cisplatin, an important antitumoral agent, was conducted to combine the best features of both compounds. A search for the most stable structure of the platinum(II)-PZA complex at a 2:1 stoichiometry: diclorodi(pyrazinamido)platinum(II), or cis-[PtCl2(PZA)2], was performed, using functional theory (DFT) associated to a mixed-level factorial design of two factors type 5 × 3, totaling 15 experiments. After evaluating the response surface and following the performance of seven experiments to validate the area identified as optimal, the most stable structure is that in which the dihedral 2Cl/1Pt/5O/7C is at an 18.9° angle.

Um método de redissolução para a determinação do agente anti-retroviral efavirenz em concentrações submicromolares e meio eletrolítico alcalino diluído é descrito. As condições experimentais ótimas encontradas são: NaOH 2,0 × 10-3 mol L-1, potencial de acumulação -0,10 V, amplitude de pulso 50 mV e velocidade de varredura 50 mV s-1. A resposta é linear sobre a faixa de concentrações 0,01-0,25 ppm. Para um tempo de acumulação de 10 min, o limite de detecção encontrado foi igual a 1,0 ppb (3,0 × 10-9 mol L-1). As condições mais convenientes para a medida da concentração de efavirenz na presença de ATP, DNA, diversos metais e outros antivirais foi também investigada. A utilidade do método é demonstrada pela determinação de efavirenz em uma mistura sintética contendo lamivudina e zidovudina, drogas frequentemente usadas na clínica em associação com o efavirenz como parte da terapêutica anti-retroviral de alta ação (HAART).

A stripping method for the determination of the antiretroviral drug efavirenz at the submicromolar concentration levels in diluted alkaline electrolyte is described. Optimum experimental conditions were: 2.0 × 10-3 mol L-1 NaOH, accumulation potential of -0.10 V, pulse amplitude of 50 mV and scan rate of 50 mV s-1. The response is linear over the concentration range of 0.01-0.25 ppm. For an accumulation time of 10 min, the limit of detection was 1.0 ppb (3.0 × 10-9 mol L-1). The most convenient conditions to measure the efavirenz concentration in the presence of ATP, DNA, several metals, and other antiviral drugs was also investigated. The utility of the method is demonstrated by the determination of efavirenz in a synthetic mixture containing both lamivudine and zidovudine, which are frequently used in the clinic in association with efavirenz as part of highly active antiretroviral therapy (HAART).

Três novos complexos de cobre(II) com os ligantes quinuclidina [Cu(C7H13N)2(OH2)Cl]Cl·2H 2O (1), quinina [Cu(C20H23O2N2)(OH 2)2]ClO4 (2) e hidroquinidina [Cu(C20H27O2N2)(OH 2)Cl2]Cl·½H2O (3) foram isolados e caracterizados. Os sítios de ligação foram atribuídos com base nos resultados de espectroscopia vibracional, ressonância paramagnética eletrônica e análise térmica. A possibilidade de envolvimento do nitrogênio quinuclidínico na coordenação foi evidenciada no complexo 1, no qual o cobre(II) está coordenado a duas moléculas de quinuclidina. No caso dos ligantes análogos à quinina, se o material de partida estiver desprotonado em ambos os nitrogênios, a coordenação do cobre(II) ocorrerá através do nitrogênio quinuclidínico, como no complexo 2. Por outro lado, se o material de partida estiver protonado no nitrogênio quinuclidínico, o sítio de ligação será o nitrogênio quinolínico, como no complexo 3. Estes resultados evidenciam que ambos os nitrogênios de ligantes da família da quinina constituem sítios de ligação para íons cobre(II).

Three new copper(II) complexes with the ligands quinuclidine [Cu(C7H13N)2(OH2)Cl]Cl·2H 2O (1), quinine [Cu(C20H23O2N2)(OH 2)2]ClO4 (2), and hydroquinidine [Cu(C20H27O2N2)(OH 2) Cl2]Cl·½H2O (3) have been isolated and characterized. The binding sites were assigned on the basis of vibrational spectroscopy, electron paramagnetic resonance, and thermal analysis results. The possibility of the involvement of the quinuclidinic nitrogen in the coordination was evidenced in complex 1, in which copper(II) is coordinated to two quinuclidine molecules. In the case of quinine-type ligands, if the starting material is deprotonated in both nitrogens, copper(II) coordination occurs through the quinuclidinic nitrogen, as in complex 2. In contrast, if the starting material is protonated in the quinuclidinic nitrogen the binding site is the quinolinic nitrogen, as in complex 3. Therefore, both nitrogens of quinine-type ligands constitute binding sites for copper(II) ions.