Monique Biesemans

Synthesis, characterization and in vitro antitumor activity of di- and triorganotin derivatives of polyoxa- and biologically relevant carboxylic acids.

An overview of the development of anti-tumor organotin derivatives, sometimes as active in vitro as doxorubicin, is presented and discussed. Solubility in water is an important issue, dominating the in vivo testing of compounds with promising in vitro properties. Several water-soluble organotin compounds gave the best in vitro activities. Novel, useful organotin anti-tumor compounds should be designed toward improved water solubility.

Low-temperature synthesized aluminosilicate glasses

The reaction below 100 °C of a dehydroxylated clay (metakaolinite: (Al2O3)(SiO2)2(H2O)0.05) suspended in an alkaline sodium silicate solution ((Na2O)(SiO2)1.4(H2O)x) leads to an amorphous glassy aluminosilicate, called in this work “low-temperature inorganic polymer glass” (LTIPG or IPG).The IPG material is amorphous according to X-ray diffraction (XRD). Its molecular structure is determined by solid state Al and Si magic angle spinning nuclear magnetic resonance (27Al and 29Si MAS NMR) spectroscopy. The polymer consists of SiO4 and AlO4 tetrahedra randomly distributed, with the restriction that no Al-O-Al bonds occur. The Al/Na ratio equals one, the overall cross-link density is almost four, and only few Si-OH groups are present.The reaction stoichiometry is deduced from differential scanning calorimetry (DSC) and 27Al and 29Si MAS NMR. The inorganic polymer glass is formed by the low-temperature reaction of silicate and metakaolinite in a one to one ratio, according to the following overall reaction equation (Na2O)(SiO2)1.4(H2O)x + (Al2O3)(SiO2)(H2O)0.05 aq.(< 100 °C) →(Na2O)(Al2O3)(SiO2)3.4(H2O)z with z about 0.4.Mechanical testing shows that the ultimate compressive strength of the inorganic polymer glass corresponds with the stoichiometric silicate/metakaolinite one to one mixing ratio.

Low-temperature synthesized aluminosilicate glasses: Part III Influence of the composition of the silicate solution on production, structure and properties

The low-temperature reaction between an aqueous sodium or potassium silicate solution and metakaolinite yields a solid aluminosilicate. The influence of the molar ratios H2O/R2O (between 6.6 and 21.0) and SiO2/R2O (between 0.0 and 2.3) of the silicate solution (R=Na or K) on the aluminosilicates production, on the reaction stoichiometry and on the aluminosilicates molecular structure is studied with differential scanning calorimetry, 27Al and 29Si magic angle spinning nuclear magnetic resonance (MAS NMR), cross-polarization MAS NMR, Fourier transform infrared spectroscopy and X-ray diffractometry. The reaction stoichiometry is determined by a one to one ratio for R/Al. H2O/R2O has no influence on the molecular structure of the aluminosilicate. Aluminium in the aluminosilicate is four-fold coordinated for the whole range of silicate solutions investigated. Moreover, Si and Al are homogeneously distributed and the ratio Al/Si in the aluminosilicate is the same as in the reaction mixture if the stoichiometric one-to-one ratio for R/Al is used. If SiO2/R2O in the Na-silicate solution is equal to or higher than 0.8, the low-temperature reaction yields an amorphous aluminosilicate or “inorganic polymer glass”. For smaller values of SiO2/R2O the Na-aluminosilicates are partially crystalline. Thermomechanical analysis and dynamic mechanical analysis indicate that a variation in the composition of the amorphous aluminosilicates can shift the glass transition over a few hundreds of degrees, with a minimum value of 650°C.

Synthesis, characterization and in vitro antitumour activity of triphenyl- and tri-n-butyltin benzoates, phenylacetates and cinnamates

Spectroscopic, structural and antitumour properties of triphenyltin and tri-n-butyltin benzoates, phenylacetates and cinnamates are compared with those of their corresponding pentafluorophenyl analogues.

Dibutyltin perfluoroalkanecarboxylates: synthesis, NMR characterization and in vitro antitumour activity

Three dibutyltin perfluoroalkanecarboxylates have been synthesized, characterized by H-1-, C-13-, F-19- and Sn-117-NMR, Mossbauer, IR and mass spectroscopy. The structure of tetra-n-butylbis(trifluoroacetato)distannoxane has been elucidated by X-ray crystallography. The in vitro antitumour activity of the three compounds against seven human tumour cell lines was found to be as high as or even higher than that for reference compounds used clinically

(2-Methylthio-3-Pyridinecarboxylato)-diethyltin and -di-n-butyltin compounds: synthesis, spectroscopic characterization and in vitro antitumour activity. X-ray crystal structure of bis[diethyl(2-methylthio-3-Pyridinecarboxylato)tin] oxide and of diethyltin bis(2-methylthio-3-pyridinecarboxylate)

The X-ray crystal structures of [diethyl(2-methylthio-3-pyridinecarboxylato)tin] oxide (1a) and diethyltin bis(2-methylthio-3-pyridinecarboxylate) (1b) were determined. Compound 1a is a centrosymmetric dimer with two distinct types of carboxylate moieties and tin atoms with trigonal bipyramidal geometries. Compound 1b is monomeric with a six-coordinate tin atom and two equivalent carboxylate groups chelating the tin atom. Compounds 2a and 2b, the di-n-butyl analogues of 1a and 1b, have also been synthesized and characterized spectroscopically. The in vitro activity of compounds 2b and 2a against the human tumour cell line WiDr, a colon carcinoma, is better than that of cis-platin and doxorubicin. They are much less active than doxorubicin against MCF-7, a mammary tumour cell line. Compound 1b is inactive.

Synthesis and characterization of triphenyl- and tri-n-butyltin pentafluorobenzoates, -phenylacetates and -cinnamates. X-ray structure determination of tri-n-butyltin pentafluorocinnamate

A crystal structure analysis of F5C6CH  CHCOOSnBu3 shows that the compound is polymeric because of the presence of bidentate carboxylate ligands bridging two tin atoms in trans-R3SnO2 arrangement. This results in a five-coordinated trigonal-bipyramidal geometry around the tin atom with two apical oxygen atoms and three equatorial butyl groups. Mossbauer and CP-MAS 117Sn NMR data for triphenyl- and tri-n-butyltin pentafluorobenzoates, -phenylacetates and cinnamates, taking the X-ray structure of F5C6CHCHCOOSnBu3 as a reference, converge to similar polymeric five-coordinated structures in the solid state. In contrast, 13C and 119Sn NMR data in chloroform solution unambiguously indicate tetrahedral four-coordination at tin for all compounds. Failing aromatic 13C chemical shift increments and complex nJ(13C19F) multiplet patterns necessitated recording of 2D 19F13C HMQC spectra in order to fully characterize the new compounds in solution.

Synthesis, Characterization and In Vitro Antitumour Activity of Di-n-Butyl, Tri-n-Butyl and Triphenyltin 3,6-Dioxaheptanoates and 3,6,9-Trioxadecanoates.

A series of di- and triorganotin 3,6-dioxaheptanoates and 3,6,9-trioxadecanoates were synthesized and characterized by 1H, 13 and 117Sn NMR, electrospray mass and 119mSn Mössbauer spectroscopy, as well as elemental analysis. Their in vitro antitumour activity against seven tumoural cell lines of human origin, two breast cancers (MCF-7, EVSA-T), a colon carcinoma (WiDr), an ovarian cancer (IGROV), a melanoma (M 19 MEL), a renal cancer (A 498) and a non small cell lung cancer (H 226), is reported. They are characterized by similar inhibition doses ID50 as the analogous di- and triorganotin derivatives of 4-carboxybenzo-15-crown-5 and -18-crown-6 and in some cases by much lower ID50 values than clinically used reference compounds such as doxorubicine and methotrexate.

Synthesis and characterization of triphenyl-, tri-n-butyl and di-n-butyltin derivatives of 4-carboxybenzo-18-crown-6 and -15-crown-5

Abstract 1H-, 13C- and 117Sn-NMR as well as 119mSn Mossbauer spectroscopy, electrospray mass spectrometry and elemental analysis of novel trioganotin and di-n-butyltin derivatives of 4-carboxybenzo-18-crown-6 and -15-crown-5 are reported. The X-ray crystal structure of aquatriphenyltin-4,7,10,13,16-pentaoxadicyclo[13.4.0]nonadeca-1,3(17),18-trienecarboxylate hydrate consists of trigonal bipyramidal tin with a C3 trigonal plane and the axial positions occupied by an oxygen atom, derived from a monodentate carboxylate ligand, and a water molecule. In the lattice, the crown ether portions of the molecules are capped on either side, via hydrogen bonding interactions, by the coordinated and uncoordinated water molecules.

Crystal structure of the dimeric bis(p-fluoro- and pentafluorophenylacetato)tetra-n-butyldistannoxanes

Abstract The crystal structures of bis(pentafluorophenylacetato)tetra-n-butyldistannoxane, [nBu2Sn(O2CCH2C6F5)]2O2 (1 and bis(p-fluoro-phenylacetato)tetra-n-butyldistannoxane, ([nBu2Sn(O2CCH2C6H4F-p)]2O2 (2) are reported. The compounds are shown to have different dimeric structures in the crystalline state despite their structural similarity. The structures each have a centrosymmetric nBu4Sn2O2 core to which are bonded two nBu2Sn moieties. The main difference between the two structures involves the mode of attachment of one of the independent carboxylate ligands. In 1, the ligand is bidentate, bridging a pair of endo- and exo-cyclic Sn atoms by using both O atoms, whereas in 2, the comparable ligand bridges the Sn atoms by using one O atom only. The second independent carboxylate ligand is coordinated exclusively to the exocyclic Sn atom in each case. The great similarity of their NMR spectra reveals that compounds 1 and 2 have identical structures in CDCl3 solution. The NMR data indicate also the existence of a dynamic process involving averaging of the carboxylate but not the diorganotin resonances, as observed previously; a process accounting for the fluxionality is proposed. A dissociation/reassociation mechanism involving an averaging equilibrium between dimeric and monomeric distannoxanes can be formally excluded.