Martine Kemmer

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.

Interactions of two cytotoxic organotin(IV) compounds with calf thymus DNA

The reactions with DNA of two antitumor active organotin(IV) compounds, the dimer of bis[(di-n-butyl 3,6-dioxaheptanoato)tin] (C(52)H(108)Sn(4)O(1) x 2H(2)O), compound 1, and tri-n-butyltin 3,6,9-trioxodecanoate (C(19)H(40)SnO(5) x 1/2H(2)O), compound 2, were analysed by circular dichroism, DNA melting experiments and gel mobility shift assays. It is found that both complexes modify only slightly the B-type circular dichroism spectroscopy (CD) spectrum of calf thymus DNA. On the other hand, both complexes were found to affect significantly the parameters of the thermally induced helix-to-coil transition. Addition of 1 or 2 to calf thymus DNA samples does not favor DNA renaturation after melting ruling out formation of interstrand crosslinks. Moreover, the effects of both compounds on plasmid DNA gel mobility were investigated. From the analysis of the present results it is inferred that both organotin(IV) compounds do interact with DNA, probably at the level of the phosphate groups.

Organotin(IV) derivatives of 3,4-(methylenedioxy)phenylacetic acid: Synthesis, spectroscopic characterization and in vitro antitumour properties

The triphenyltin and tri-n-butyltin 3,4-(methylenedioxy)phenylacetates as well as the tetra-n-butylbis[3,4-(methylenedioxy)phenylacetato]distannoxane dimer have been synthesized and characterized by H-1, C-13, Sn-117 NMR, Sn-119m Mossbauer and mass spectroscopy. The compounds have been screened against a panel of tumour cell lines of human origin.

Synthesis, spectroscopy and structure of [N-(2-carboxyphenyl)salicylideneiminato]dimethyltin(IV)

Abstract The novel dimethyltin complex with formula Me 2 Sn(2-OC 6 H 4 CHNC 6 H 4 COO), compound 1 , involving the Schiff base derived from anthranilic acid and salicylaldehyde, has been synthesized and characterized by elemental analysis, IR, 1 H-, 13 C- and 117 Sn-NMR, 119 Sn Mossbauer spectroscopy and single-crystal X-ray diffraction structure analysis. The crystals of complex 1 are monoclinic, space group P 2 1 / n , a =8.907(5), b =12.044(7), c =14.062(9) A, β =104.99(5)°, Z =4, R 1 =0.0296, wR 2 =0.08 for 1368 observed reflections. The crystal structure of 1 features centrosymmetric dimers disposed about a central Sn 2 O 2 core. The tin environment is seven-coordinate if a moderately long contact distance Sn(1)O(2a) (2.69(1) A) and a longer one Sn(1)O(3a) (3.03(1) A) are included in the coordination list. In the basic monomeric structural unit, the tin configuration can be seen as a distorted square-pyramid with the imine nitrogen atom in apical position, the N -(2-carboxyphenyl)salicylideneimine dianion coordinating a single tin atom via the phenolate oxygen atom, the imine nitrogen atom and one of the carboxylate oxygen atoms. The distortion of the square pyramid is discussed in terms of a trend to trigonal-bipyramidal geometry.

Complexation of triorganotin derivatives of [18]crown-6- and [15]crown-5-(benzo-4-carboxylate) with alkali thiocyanates

Investigations of the simultaneous complexation of tri-n-butyltin and triphenyltin derivatives of [18]crown-6- or [15]crown-5-(benzo-4-carboxylate) by the anion and cation from NaSCN or KSCN are reported. The crystal structure of [Na+ is included in [15]crown-5-C6H3-4-COOSn(C6H5)3NCS]-], 4 NaSCN, displays an unusual zwitterionic nature with one intramolecular charge separation characterized by an Na-Sn distance of 9.29(1) A, and several intermolecular charge separations, the shortest being 5.48(1) A. Similar distances (9.70(2), 9.28(2), intramolecular; 5.40(2) and 5.41(2) A, shortest intermolecular) are observed in the more complicated structure of the corresponding [18]crown-6-(benzo-4-carboxylate) derivative, 3 NaSCN, with two independent molecules in the asymmetric unit. For the tri-n-butyltin analogues 1 and 2, complex equilibria were observed in acetone and unraveled by variable temperature 13C, 117Sn. and 23Na NMR studies. Their complexes with KSCN and NaSCN undergo decomposition in acetone solution, as evidenced by the transformation of [K+ is included in [18]crown-6-[C6H3-4-COOSn(nBu)3NCS]-], into tri-n-butyltin isothiocyanate and a novel dimeric potassium [18]crown-6-(benzo-4-carboxylate), the structure of which was elucidated by X-ray diffraction analysis.

Synthesis and structures of intramolecularly hexacoordinated organotin chlorides containing the (3-(2-methoxy)ethoxy) propyl moiety

Abstract Two water-soluble organotin compounds, (3-(2-methoxy)ethoxy)propyltin trichloride, 1 , and bis (3-(2-methoxy)ethoxy)propyltin dichloride, 2 , were synthesized and characterized by 1 H, 13 C and 119 Sn NMR spectroscopy and by X-ray diffraction. In both cases, the geometry at the tin atom is that of a distorted cis -octahedron, which is preserved for both compounds in CDCl 3 solution. A detailed solution structure is proposed for 1 from ID 1 H- 119 Sn HMQC NMR experiments.

Synthesis and structural characterization of (4,7-dioxaoctyl)phenyldichlorostannane and triphenyltin compounds containing various polyoxaalkyl moieties

Abstract The synthesis and characterization of (4,7-dioxaoctyl)triphenyltin (1), (4,7,10-trioxaundecyl)triphenyltin (2), (4,7,10,13-tetraoxatetradecyl)triphenyltin (3), and (4,7-dioxaoctyl)phenyldichlorostannane (4) are reported. Investigatons using 1H-, 13C-, and 119Sn-NMR, gradient assisted 2D 1H–13C HMBC and HMQC NMR, 1D 1H–119Sn HMQC NMR demonstrate that 1–3 are essentially tetracoordinated. By contrast, the structure of compound 4, determined by X-ray diffraction methods, reveals a hexacoordinated, distorted octahedral geometry, in which the 4,7-dioxaoctyl ligand is tridentate, with a facial arrangement of the C, O, O atoms with respect to tin. NMR investigations reveal that this structure exists in solution, but is labilized by a double ring opening–closing mechanism.

CRYSTAL STRUCTURE OF ZIG-ZAG POLYMERIC TRI-n-BUTYLTIN(IV) 3,4-METHYLENEDIOXYPHENYLACETATE

1 Free University of Brussels ULB, Chimie Organique. Av. F. D. Roosevelt. 50, B-1050 Bruxelles. Belgium 2 Free University of Brussels VUB, Pleinlaan 2, B-1050 Brüssel. Belgium a General and Organic Chemistry Unit AOSC. Faculty of Applied Sciences ° High Resolution NMR Center HNMR 3 Universidad Autonoma Metropolitana. Uni dad Xochimilco, Departamento de Sistemas Biologicos, Calzada del Hueso 11(X), Col. Villa Quietud, 04960 Mexico D. F. 4 Department of Chemistry, National University of Singapore. Singapore 117543

The crystal structure of a distannoxane containing 4-carboxybenzo-15-crown-5 ligands

The X-ray crystal structure of {[nBu2Sn(02CR)]20}2, where R is 4-benzo-15-crown-5, shows the molecule to be centrosymmetric and comprises a central Sn202 core to which are linked to two exocyclic tin atoms. Almost symmetric carboxylate bridges provide additional links between pairs of endoand exo-cyclic tin atoms and the remaining carboxylate ligands are monodentate, coordinating the exocyclic tins exclusively. The coordination geometries are distorted trigonal bipyramidal. 1 . In t roduct ion Organotin compounds with carboxylate ligands containing crown ether residues have received attention as a part of an on-going study of the anti-tumour activity of organotins [1-3]. Thus, both triorganotin and diorganotin species containing either 4-carboxybenzo-18-crown-6 or 4carboxybenzo-15-crown-5 ligands have been characterized [4], The in vitro anti-tumour activities of a series of analogous compounds have been reported [5], Subsequently, crystals of the title compound have been isolated and its crystal structure determined. The results of this study are reported herein. 2 . Exper imenta l 2 . 1 Syn thes is The compound was prepared as reported previously [4], Crystals were isolated from the recrystallisation from hexane/chloroform. 2 . 2 . Crystal lography Intensity data for a colourless crystal (0.23 χ 0.26 χ 0.45 mm) were measured at 173 Κ on a Rigaku AFC7R diffractometer using MoKa radiation (λ = 0.71073 Ä) and the ω:2θ scan technique so that 6max was 30°. Of the 14499 data collected, 13993 were unique and these were corrected for Lorentz and polarization effects [6] as well as for absorption employing an empirical procedure [7] (min/max. transmission factors: 0.947 1). The structure was solved by direct-methods [8] and refined by a full-matrix least-squares procedure based on Fusing 9851 reflections with /> 3.0σ(/) [6]. With the exception of a disordered η-butyl group, non-hydrogen atoms were refined with anisotropic displacement parameters and hydrogen atoms were included in the model in their calculated positions. The η-butyl group containing the atoms C(43)-C(46) was found to be disordered (statically) so that each of the C(44) and C(45) atoms were distributed over two distinct sites of equal weight; for this group the carbon atoms were refined isotropically and hydrogen atoms were not included. The refinement was continued until convergence employing a weighting scheme of the form w = 1 /[<?{F0) + 0 .00037IF/ ] yielding final R and Fl of 0.034 and 0.046, respectively. The largest residual in the final difference map was 1.12 eÄ 3 which was located in the vicinity of the disordered η-butyl residue. Final refinement details are listed in and the numbering scheme employed is shown in Figure 1 which was drawn with ORTEP [9] at the 50 % probability level. Crystallographic data have been deposited at the CCDC with deposition number CCDC 140263. Copies of this data may be obtained free of charge from The Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, England (Facsimile: 44-1223-336033 ore-mail: deposit@ccdc.cam.ac.uk).

THE CRYSTAL STRUCTURE OF BIS[(3,4-(METHYLENE-DIOXYPHENYLACETATO)-DI-n-BUTYLTIN]OXIDE

ι a Free University of Brussels VUB, Pleinlaan 2 h B 1 0 5 0 Brussels, Belgium AOSC Department, Faculty of Applied Sciences; High Resolution NMR Centre Present address: Universidad Autonoma Metropolitana. Unidad Xochimilco, Departamento de Sistemas Biologicos, Calzada del Hueso 1100, Col. Villa Quietud, 04960 Mexico D. F. 1 Department of Chemistry, Rikkyo University, Nishi-lkebukuro, Tokyo 171-8501, Japan and Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan Department of Chemistry, The University of Adelaide, Australia 5005