Organotin(IV)ⁿ⁺ complexes formed with biologically active ligands: equilibrium and structural studies, and some biological aspects

Abstract

The organotin(IV) cations form complexes with ligands containing {O}, {N}, {S}, or {phosphorus(O)} donor atoms with various composition and stability. The emergence of new experimental techniques (EXAFS, multinuclear ¹H-, ¹³C-, ¹¹⁹Sn-NMR, ¹¹⁹Sn Mössbauer, etc., spectroscopic techniques) provided useful information about the structure and stabilities of the complexes formed. We reviewed the literature on these type of complexes taking into account the biological aspects of the complexes discussed.

Introduction

The rapid rise in the industrial, agricultural and biological applications of organotin(IV) compounds during the last few decades has led to their accumulation in the environment and in biological systems.

Organotin(IV) compounds are characterized by the presence of at least one covalent CSn bond. The compounds contain tetravalent Sn centres and are classified as mono-, di-, tri- and tetraorganotin(IV)s, depending on the number of alkyl (R) or aryl (Ar) moieties. The anion is usually chloride, fluoride, oxide, hydroxide, a carboxylate or a thiolate.

It is well known that organotin(IV) compounds display strong biological activity. Most organotin(IV) compounds are generally very toxic, even at low concentration. The biological activity is essentially determined by the number and nature of the organic groups bound to the central Sn atom. It seems that the nature of the anionic group is of only secondary importance. The trialkyltin(IV) [R₃Sn(IV)⁺] and triaryltin(IV) [Ar₃Sn(IV)⁺] derivatives exert powerful toxic action on the central nervous system. Within the series of R₃Sn(IV)⁺ compounds, the lower homologues (methyl, Me; ethyl, Et) are the most toxic when administrated orally, and the toxicity diminishes progressively from tri-n-propyl to tri-n-octyl, the latter not being toxic at all.

The moieties R_nSn(IV)⁽⁴⁻ⁿ⁾⁺ (n=2 or 3) may be bound to membrane proteins or glycoproteins, or to cellular proteins; e.g. Et₂Sn(IV)²⁺ to ATPase and hexokinase [1], Bu₂Sn(IV)²⁺ and Bu₃Sn(IV)⁺ to ATPase and acetylcholinesterase of human erythrocyte membrane [2], [3], while Bu₂Sn(IV)²⁺ may also be bound to skeletal muscle membranes. It seems that the sulfur-coordinated complexes are very stable as compared with those coordinated by {O} or {N}. Some organotin(IV) compounds have antitumour activity [4]. The antitumoural mechanism remains unknown (see later).

Several surveys of organotin(IV) compounds have been published. Zuckerman reviewed much of the work published before 1978 [5], while in 1989 Saxena and Huber [4] covered the literature dealing with the biological, including the anticancer activities, of most of the compounds studied. In the same year, the results obtained in the wide field of bioorganotin(IV) compounds were surveyed by Molloy [6]. Later, Tsangaris and Williams [7] published a paper on Sn [including organotin(IV)], compounds in pharmacy and nutrition. A full listing of reports which have evaluated organotin(IV) compounds in agriculture is to be found in the two-part review by Crowe [8], [9]. Detailed discussions of organotin(IV) wood preservatives are published in [10], [11].

In 1985, two independently published reviews demonstrated the utility of organotin(IV) derivatives of (poly)alcohols in regioselective manipulations involving indirect acylation, alkylation and oxidation [12], [13], while a very recent work by Grindley dealt with the applications of organotin(IV)-containing intermediates in carbohydrate chemistry [14].

Strong sugar-organotin(IV) cation complexation have been discussed by Burger and Nagy [15], Gyurcsik and Nagy [16], Verchére et al. [17], while Barbieri et al. [18] dealt mainly with the interactions of organotin(IV) cations and complexes with DNA and their derivatives. However, a comprehensive review of the properties of the organotin(IV) complexes formed with biologically active ligands is not yet available. The aim of the present work is to survey the results obtained by means of different equilibrium (mainly pH-metric, spectrophotometric and calorimetric) and structural [spectroscopic (multinuclear NMR, FTIR and Mössbauer), X-ray diffraction, extended X-ray absorption fine structure (EXAFS) and X-ray absorption near edge structure (XANES) measurements, etc.] methods on the complexes formed with the various organotin(IV) ions or compounds. The biological properties of some of the compounds in question are also discussed.