The mononuclear diamagnetic compound {Fe(bztpen)[N(CN)2]}(PF6)CH3OH (1) (bztpen = N-benzyl-N,N',N'-tris(2-pyridylmethyl)ethylenediamine) has been synthesized and its crystal structure studied. Complex 1 can be considered to be the formal precursor of two new dinuclear, dicyanamide-bridged iron(II) complexes with the generic formula {[(Fe(bztpen)]2[mu-N(CN)2]}(PF6)3 x n H2O (n = 1 (2) or 0 (3)), which have been characterized in the solid state and in solution. In all three complexes, the iron atoms have a distorted [FeN6] octahedral coordination defined by a bztpen ligand and a terminal (1) or a bridging dicyanamide ligand (2 and 3). In the solid state, 2 and 3 can be considered to be molecular isomers that differ by the relative position of the phenyl ring of the two {Fe(bztpen)[N(CN)2]}+ halves (cis and trans, respectively). Depending on the texture of the sample, 2 exhibits paramagnetic behavior or displays a very incomplete spin transition at atmospheric pressure. Complex 3 undergoes a gradual two-step spin transition with no observed hysteresis in the solid state. Both steps are approximately 100 K wide, centered at approximately 200 K and approximately 350 K, with a plateau of approximately 80 K separating the transitions. The crystal structure of 3 has been determined in steps of approximately 50 K between 400 K and 90 K, which provides a fascinating insight into the structural behavior of the complex and the nature of the spin transition. Order-disorder transitions occur in the dicyanamide bridge and the PF6(-) ions simultaneously, with the spin-crossover behavior suggesting that these transitions may trigger the two-step character. In solution, 2 and 3 display very similar continuous spin conversions. Electrochemical studies of 2 and 3 show that the voltammograms are typical of dimeric systems with electronic coupling of the metals through the dicyanamide ligand.

In several studies of patients with neurocysticercosis under treatment with albendazole the pharmacokinetic data were difficult to interpret, probably because of slow and erratic drug dissolution response and absorption problems in-vivo. Because there is no information available about the physicochemical properties of the drug, the aim of this work was to explain this erratic behaviour by fully characterizing the solution behaviour of the drug and its metabolite. To accomplish this, the physicochemical properties, pKa and solubility, and in-vitro plasma binding of albendazole and its main metabolite, albendazole sulphoxide, were studied by conventional methods. The intestinal and gastric absorption and dissolution behaviour of albendazole were also studied. The solubility of both compounds is very low. Both are amphoteric molecules with two ionization steps, with pKa values of 10.26 and 2.80 for albendazole and 9.79 and 0.20 for albendazole sulphoxide; low pKa values were obtained by performing linear free energy relationship calculations. On the other hand, protein binding studies showed that albendazole is 89-92% bound to plasma proteins whereas for albendazole sulphoxide the figure is 62-67%. This metabolite is bound by albumin and to alpha1-glycoprotein. Absorption of albendazole occurs along the gastrointestinal tract and is limited by its solubility. Good dissolution profiles were observed when 0.1 M HCl was used as dissolution medium. The results show that 0.1 M HCl enables discrimination between the drug-release characteristics of different products.

The aim of this work is to describe the specific recognition site between DNA and an anticancer copper complex by means of computational methods. Molecular dynamics were used to find the preferred site of binding between selected DNA chains and [Cu(2,2'-bipyridine)(acetylacetonate)(H(2)O)](+) (Cas). Full DFT optimizations of selected geometries extracted from simulations, followed by a topological analysis of electron density allowed us to define the specific interactions inside the recognition site. Cas links deoxyribose-phosphate by a coordination bond between metal and the phosphate group. There are several C-H···π, O···π(C) and O···π(N) interactions between the sugar group and the aromatic ligand of Cas. The results indicate that the adduct Cas-deoxyribose-phosphate may be an initial step toward the hydrolysis of DNA chains. Overall, this study provides insights into the initial step of the action mechanism of copper complexes as apoptosis-inducing agents and provides guidelines for the design of this kind of drugs.

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