To what extent can cyclometalation promote associative or dissociative ligand substitution at platinum(II) complexes? A combined kinetic and theoretical approach

The ligand exchange rate constants for the reactions [Pt(bph)(SR2)2] + 2*SR2 --> [Pt(bph)(*SR2)2] + 2SR2 (bph = 2,2'-biphenyl dianion; R = Me and Et) and cis-[PtPh2(SMe2)2] + 2*SMe2 --> cis-[PtPh2(*SMe2)2] + 2SMe2 have been determined in CDCl3 as a function of ligand concentration and temperature, by 1H NMR isotopic labeling and magnetization transfer experiments. The rates of exchange show no dependence on ligand concentration and the kinetics are characterized by largely positive entropies of activation. The kinetics of displacement of the thioethers from [Pt(bph)(SR2)2] with the dinitrogen ligands 2,2'-bipyridine and 1,10-phenanthroline (N-N) to yield [Pt(bph)(N-N)], carried out in the presence of sufficient excess of thioether and N-N to ensure pseudo-first-order conditions, follow a nonlinear rate law k(obsd) = a[N-N]/(b[SR2] + [N-N]). The general pattern of behavior indicates that the rate-determining step for substitution is the dissociation of a thioether ligand and the formation of a three-coordinated [Pt(bph)(SR2)] intermediate. The value of the parameter a, which measures the rate of ligand dissociation, is constant and independent of the nature of N-N, and it is in reasonable agreement with the value of the rate of ligand exchange at the same temperature. Theoretical ab initio calculations were performed for both [Pt(bph)(SMe2)2] and cis-[PtPh2(SMe2)2], and for their three-coordinated derivatives upon the loss of one SMe2 ligand. The latter optimize in a T-shaped structure. Calculations were performed in the HF approximation (LANL2DZ basis set) and refined by introducing the correlation terms (Becke3LYP model). The activation enthalpies from the optimized vacuum-phase geometries are 52.3 and 72.2 kJ moll compared to the experimental values in CDCl3 solution, 80 +/- 1 and 93 +/- 1 kJ mol(-1) for [Pt(bph)(SMe2)2] and cis-[PtPh2(SMe2)2], respectively. The electrostatic potential maps of both parent compounds show a remarkable concentration of negative charge over the platinum atom which exerts a repulsion force on an axially incoming nucleophile. On the other hand, the strength of the organic carbanions trans to the leaving group and the stabilization of the T-shaped intermediate in the singlet ground state may also rationalize the preference for the dissociative mechanism. All of the kinetic and theoretical data support the latter hypothesis and indicate, in particular, that dissociation from the complex containing the planar 2,2'-biphenyl dianion is easier than from its analogue with single aryl ligands. Electron back-donation from filled d orbitals of the metal to empty pi* of the in-plane cyclometalated rings is weak or absent and is not operative in promoting an associative mode of activation.     

Synthesis of 3‐imidazolylazole derivatives from a new nitrile oxide

The synthesis of a series of 3‐Imidazolylazole derivatives using cycloaddition reactions of a useful new nitrile oxide is described.     

Analysis of iron state in some Argentinian soils by dissolution methods and Mössbauer spectroscopy

Bahia Blanca (Argentina) soils, in particular entisols, are studied by Mössbauer spectroscopy. X-ray diffraction and scanning electron microscopy are used to characterize the samples. Samples were treated with different chemical iron extraction methods, in order to determine relative Fe_o and Fe_d fractions. The Fe_o/Fe_d ratios are obtained and the relative effect of iron extraction treatment on spectra components are determined. In addition, the effect of extraction procedures, dithionite-citrate-bicarbonate and oxalate, in the residual soil fraction are analyzed.     

Scleroglucan: a versatile polysaccharide for modified drug delivery

Scleroglucan is a natural polysaccharide, produced by fungi of the genus Sclerotium, that has been extensively studied for various commercial applications (secondary oil recovery, ceramic glazes, food, paints, etc.) and also shows several interesting pharmacological properties. This review focuses its attention on the use of scleroglucan, and some derivatives, in the field of pharmaceutics and in particular for the formulation of modified-release dosage forms. The reported investigations refer mainly to the following topics: natural scleroglucan suitable for the preparation of sustained release tablets and ocular formulations; oxidized and crosslinked scleroglucan used as a matrix for dosage forms sensitive to environmental conditions; co-crosslinked scleroglucan/gellan whose delivery rate can be affected by calcium ions. Furthermore, a novel hydrogel obtained with this polysaccharide and borate ions is described, and the particular structure of this hydrogel network has been interpreted in terms of conformational analysis and molecular dynamics. Profound attention is devoted to the mechanisms involved in drug release from the tested dosage forms that depend, according to the specific preparation, on swelling and/or diffusion. Experimental data are also discussed on the basis of a mathematical approach that allows a better understanding of the behavior of the tested polymeric materials.     

Molecular determinants for drug—receptor interactions: Part 2. An ab initio molecular orbital and dipole moment study of the novel nootropic agent piracetam (2-oxopyrrolidin-1-ylacetamide)

From the ab initio molecular energies of the possible conformers and from a classical dipole moment analysis of 2-oxopyrrolidin-1-ylacetamide (υ = 4.02 D in dioxan at 30.0°C), the preferred conformation in solution of this novel nootropic agent has been determined. The exocyclic NCH₂ bond is rotated in one sense by 90° and the exocyclic CH₂C bond rotated in the same sense by 120° from the “planar” (OO)-cis conformation. The structures of the two enantiomers in solution differ from that of the crystalline molecule.