Andrew Duthie

Intramolecularly Coordinated Telluroxane Clusters and Polymers

The stoichiometrically controlled chlorination of the diarylditelluride (8-Me(2) NC(10) H(6) Te)(2) with SO(2) Cl(2) afforded the aryltellurinyl chloride 8-Me(2) NC(10) H(6) TeCl (1) and the aryltellurium trichloride 8-Me(2) NC(10) H(6) TeCl(3) (2). Alternatively, 1 was obtained by the reaction of the aryltellurenyl diethyldithiacarbamate 8-Me(2) NC(10) H(6) Te(S(2) CNEt(2) ) with hydrochloric acid. The base hydrolysis of 2 provided the novel telluroxanes (8-Me(2) NC(10) H(6) Te)(2) OCl(4) (3), (8-Me(2) NC(10) H(6) Te)(6) O(5) Cl(8) (4), (8-Me(2) NC(10) H(6) Te)(6) O(8) Cl(2) (5), [(8-Me(2) NC(10) H(6) Te)(2) O(3) ](n) (6) and (8-Me(2) NC(10) H(6) Te)(6) O(8) (OH)(2) (7) depending on the reaction conditions applied. The reaction of 7 with ClTe(OiPr)(3) in the presence of water gave rise to the telluroxane (8-Me(2) NC(10) H(6) Te)(6) Te(2) O(12) Cl(2) (8). The crystal and molecular structures of 1-3 and 5-8 were determined by X-ray crystallography. The telluroxane clusters and polymers 6-8 hold potential as model compounds for alkali tellurite glasses (M(2) O)(x) (TeO(2) )(1-x) (M=Li, Na, K) for which no precise structural data are available.

Prevalence of the thioamide {⋯H–N–CS}2 synthon—solid-state (X-ray crystallography), solution (NMR) and gas-phase (theoretical) structures of O-methyl-N-aryl-thiocarbamides

Structural investigations, i.e. solid-state (X-ray), solution (1H NMR) and gas-phase (theoretical), on molecules with the general formula MeOC(S)N(H)C6H4-4-Y: Y = H (1), NO2 (2), C(O)Me (3), Cl (4) have shown a general preference for the adoption of an E-conformation about the central C–N bond. Such a conformation allows for the formation of a dimeric hydrogen-bonded {⋯H–N–CS}2 synthon as the building block. In the cases of 1–3, additional C–H⋯O interactions give rise to the formation of tapes of varying topology. A theoretical analysis shows that the preference for the E-conformation is about the same as the crystal packing stabilisation energy and consistent with this, the compound with Y = C(O)OMe, (5), adopts a Z-conformation in the solid-state that facilitates the formation of N–H⋯O, C–H⋯O and C–H⋯S interactions, leading to a layer structure. Global crystal packing considerations are shown to be imperative in dictating the conformational form of molecules 1–5.

An in vitro comparative assessment with a series of new triphenyltin(IV) 2-/4-[(E)-2-(aryl)-1-diazenyl]benzoates endowed with anticancer activities: Structural modifications, analysis of efficacy and cytotoxicity involving human tumor cell lines

Four new triphenyltin(IV) complexes of composition Ph(3)SnLH (where LH=2-/4-[(E)-2-(aryl)-1-diazenyl]benzoate) (1-4) were synthesized and characterized by spectroscopic (((1))H, ((13))C and ((119))Sn NMR, IR, ((119))Sn Mössbauer) techniques in combination with elemental analysis. The ((119))Sn NMR spectroscopic data indicate a tetrahedral coordination geometry in non-coordinating solvents. The crystal structures of three complexes, Ph(3)SnL((1))H (1), Ph(3)SnL((3))H (3), Ph(3)SnL((4))H (4), were determined. All display an essentially tetrahedral geometry with angles ranging from 93.50(8) to 124.5(2)°; ((119))Sn Mössbauer spectral data support this assignment. The cytotoxicity studies were performed with complexes 1-4, along with a previously reported complex (5) in vitro across a panel of human tumor cell lines viz., A498, EVSA-T, H226, IGROV, M19 MEL, MCF-7 and WIDR. The screening results were compared with the results from other related triphenyltin(IV) complexes (6-7) and tributyltin(IV) complexes (8-11) having 2-/4-[(E)-2-(aryl)-1-diazenyl]benzoates framework. In general, the complexes exhibit stronger cytotoxic activity. The results obtained for 1-3 are also comparable to those of its o-analogs i.e. 4-7, except 5, but the advantage is the former set of complexes demonstrated two folds more cytotoxic activity for the cell line MCF-7 with ID(50) values in the range 41-53 ng/ml. Undoubtedly, the cytotoxic results of complexes 1-3 are far superior to CDDP, 5-FU and ETO, and related tributyltin(IV) complexes 8-11. The quantitative structure-activity relationship (QSAR) studies for the cytotoxicity of triphenyltin(IV) complexes 1-7 and tributyltin(IV) complexes 8-11 is also discussed against a panel of human tumor cell lines.

Mesityltellurenyl Cations Stabilized by Triphenylpnictogens [MesTe(EPh3)]+ (E = P, As, Sb)

The homoleptic 1:1 Lewis pair (LP) complex [MesTe(TeMes2)]O3SCF3 (1) featuring the cation [MesTe(TeMes2)](+) (1a) was obtained by the reaction of Mes2Te with HO3SCF3. The reaction of 1 with Ph3E (E = P, As, Sb, Bi) proceeded with substitution of Mes2Te and provided the heteroleptic 1:1 LP complexes [MesTe(EPh3)]O3SCF3 (2, E = P; 3, E = As) and [MesTe(SbPh3)][Ph2Sb(O3SCF3)2] (4) featuring the cations [MesTe(EPh3)](+) (2a, E = P; 3a, E = As; 4a, E = Sb) and the anion [Ph2Sb(O3SCF3)2](-) (4b). In the reaction with Ph3Bi, the crude product contained the cation [MesTe(BiPh3)](+) (5a) and the anion [Ph2Bi(O3SCF3)2](-) (5b); however, the heteroleptic 1:1 LP complex [MesTe(BiPh3)][Ph2Bi(O3SCF3)2] (5) could not be isolated because of its limited stability. Instead, fractional crystallization furnished a large amount of Ph2BiO3SCF3 (6), which was also obtained by the reaction of Ph3Bi with HO3SCF3. The formation of the anions 4b and 5b involves a phenyl group migration from Ph3E (E = Sb, Bi) to the MesTe(+) cation and afforded MesTePh as the byproduct, which was identified in the mother liquor. The heteroleptic 1:1 LP complexes 2-4 were also obtained by the one-pot reaction of Mes2Te, Ph3E (E = P, As, Sb) and HO3SCF3. Compounds 1-4 and 6 were investigated by single-crystal X-ray diffraction. The molecular structures of 1a-4a were used for density functional theory calculations at the B3PW91/TZ level of theory and studied using natural bond order (NBO) analyses as well as real-space bonding descriptors derived from an atoms-in-molecules (AIM) analysis of the theoretically obtained electron density. Additionally, the electron localizability indicator (ELI-D) and the delocalization index are derived from the corresponding pair density.

SPACER-BRIDGED LADDER COMPOUNDS SYNTHESES, STRUCTURES AND SYNTHETIC APPLICATIONS

The reaction of α , ω -bis(organodichlorostannyl)alkanes [R(Cl 2 )SnCH 2 ] 2 Z with their corresponding organotin oxides [R(O)SnCH 2 ] 2 Z or ( t -Bu 2 SnO) 3 provides the new spacer-bridged tetraorganodistannoxanes {[R(Cl)SnCH 2 ] 2 Z]O} n ( 22 , Z=CH 2 , R=Me 3 SiCH 2 ; 23 , Z=CH 2 , R=Me 3 CCH 2 ; 24 , Z=CH 2 CH 2 , R=Me 3 SiCH 2 ; 25 , Z=CH 2 CH 2 , R=Me 3 CCH 2 ; 26 , Z=CH 2 CH 2 , R=Me 2 CHCH 2 ; 27 , Z=Me 2 Si, R=Me 3 SiCH 2 ). The acetate substituted derivative 28 {[R(AcO)SnCH 2 ] 2 CH 2 ]O} n (R=Me 3 SiCH 2 ) is obtained by reaction of 22 with silver acetate or by treatment of the organotin oxide [R(O)SnCH 2 ] 2 CH 2 (R=Me 3 SiCH 2 ) with acetic acid. The crystal structures of 23 , 24 , and 28 are described and reveal that these compounds adopt double ladder structures. Depending on the identity of Z and R in chloroform solution the compounds are either dimers ( n =2, 25 – 28 ) or tetramers ( n =4, 22 – 24 ). Also reported are preliminary studies on the catalytic activity in acylation reactions of compounds 22 , 24 – 26 , and 28 .

Molecular basis of the interaction of novel tributyltin(IV) 2/4-[(E)-2-(aryl)-1-diazenyl]benzoates endowed with an improved cytotoxic profile: Synthesis, structure, biological efficacy and QSAR studies

A series of tributyltin(IV) complexes based on 2/4-[(E)-2-(aryl)-1-diazenyl]benzoate ligands was synthesized, wherein the position of the carboxylate and aryl substituents (methyl, tert-butyl and hydroxyl) varies. The complexes, Bu(3)SnL(1-4)H (1-4), have been structurally characterized by elemental analysis and IR, NMR ((1)H, (13)C, and (119)Sn) and (119)Sn Mössbauer spectroscopy. All have a tetrahedral geometry in solution and a trigonal bipyramidal geometry in the solid-state, except for Bu(3)SnL(4)H (4) that was ascertained to have tetrahedral coordination by X-ray crystallography. Cytotoxicity studies were carried out on human tumor cell lines A498 (renal cancer), EVSA-T (mammary cancer), H226 (non-small-cell lung cancer), IGROV (ovarian cancer), M19 MEL (melanoma), MCF-7 (mammary cancer) and WIDR (colon cancer). Compared to cisplatin, test compounds 1-4 had remarkably good activity, despite the presence of substantial steric bulk due to Sn-Bu ligands. The quantitative structure-activity relationship (QSAR) studies for the cytotoxicity of organotin(IV) benzoates, along with some reference drug molecules, is also discussed against a panel of human tumor cell lines. Molecular structures of the tributyltin(IV) complexes (1-4) were fully optimized using the PM6 semi-empirical method and docking studies performed with key enzymes associated with the propagation of cancer, namely ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase and topoisomerase II. The theoretical results are discussed in relation to the mechanistic role of the cytotoxic active test compounds (1-4).

Synthesis and structures of new oligomethylene-bridged double ladders. How far can the layers be separated?

The synthesis of the α,ω-bis[dichloro(trimethylsilylmethyl)stannyl]alkanes, (Me3SiCH2)Cl2Sn(CH2)nSnCl2(CH2SiMe3) (13, n = 5; 14, n = 6; 15, n = 7; 16, n = 8; 17, n = 10; 18, n = 12) and the corresponding oligomethylene-bridged diorganotin oxides [(Me3SiCH2)(O)Sn(CH2)nSn(O)(CH2SiMe3)]m (19, n = 5; 20, n = 6; 21, n = 7; 22, n = 8; 23, n = 10; 24; n = 12) is reported. The reaction of the diorganodichlorostannanes 13–18 with the corresponding diorganotin oxides 19–24 provided the spacer-bridged tetraorganodistannoxanes {[(Me3SiCH2)ClSn(CH2)nSnCl(CH2SiMe3)]O}4 (25, n = 5; 26, n = 6; 27, n = 7; 28, n = 8; 29, n = 10; 30, n = 12). Compounds 13–30 have been identified by elemental analyses and multinuclear NMR spectroscopy. Compounds 25, 27, 29 and 30 have also been characterised by single crystal X-ray diffraction analysis and electrospray mass spectrometry. For the latter the essential double ladder motif is maintained for all n in the solid state, but subtle changes in alignment of the ladder planes occur. Separation between the two layers of the double ladder ranges from approx. 8.7 A (for 25, n = 5) to approx. 15 A (for 30, n = 12). In solution there is some dissociation of the double ladders into the corresponding dimers. The degree of dissociation is favoured by increasing oligomethylene chain length n.

Dibutyltin(IV) complexes containing arylazobenzoate ligands: chemistry, in vitro cytotoxic effects on human tumor cell lines and mode of interaction with some enzymes

SummaryDibutyltin(IV) complexes of composition Bu2Sn(LH)2, where LH is a carboxylate residue derived from 2-[(E)-(5-tert-butyl-2-hydroxyphenyl)diazenyl]benzoate (L1H) with water molecule (1), 4-[(E)-(5-tert-butyl-2-hydroxyphenyl)diazenyl]benzoate (L2H) (2) and 4-[(E)-(4-hydroxy-5-methylphenyl)diazenyl]benzoate (L3H) (3), were synthesized and characterized by spectroscopic (1H, 13C and 119Sn NMR, IR, 119Sn Mössbauer) techniques. A full characterization was accomplished from the crystal structure of complex 1. The molecular structures and geometries of the complexes (1a i.e. 1 without water molecule and 3) were fully optimized using the quantum mechanical method (PM6). Complexes 1 and 3 were found to exhibit stronger cytotoxic activity in vitro across a panel of human tumor cell lines viz., A498, EVSA-T, H226, IGROV, M19 MEL, MCF-7 and WIDR. Compound 3 is found to be four times superior for the A498, EVSA-T and MCF-7 cell lines than CCDP (cisplatin), and four, eight and sixteen times superior for the A498, H226 and MCF-7 cell lines, respectively, compared to ETO (etoposide). The mechanistic role of cytotoxic activity of test compounds is discussed in relation to the theoretical results of docking studies with some key enzymes such as ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase and topoisomerase II associated with the propagation of cancer.

Observation of Te…π and X…X Bonding in para-Substituted Diphenyltellurium Dihalides, (p-Me2NC6H4)(p-YC6H4)TeX2 (X = Cl, Br, I; Y = H, EtO, Me2N)

The supramolecular association of the previously described para-dimethylaminophenyl-substituted diorganotellurium dihalides (p-Me2NC6H4)2TeX2 (X = Cl (1), Br (2), I (3)) and (p-Me2NC6H4)RTeCl2 (R = Ph (4), p-EtOC6H4 (5)), was investigated by X-ray crystallography. Unlike almost all other structurally characterized diorganotellurium dihalides, (p-Me2NC6H4)2TeX2 (X = Cl (1), Br (2), I (3)) reveal no secondary Te∙∙∙X interactions, but X∙∙∙X interactions. The structure of (p-Me2NC6H4)PhTeCl2 (4) resembles that of Ph2TeCl2 and shows one secondary Te∙∙∙Cl contact, whereas (p-Me2NC6H4)(p-EtOC6H4)TeCl2 (5) exhibits neither secondary Te∙∙∙Cl nor Cl∙∙∙Cl interactions. The unusual structural characteristics of 1–5 are attributed to the occurrence of intermolecular Te∙∙∙π and π∙∙∙π contacts associated with quinoid π-electron delocalization across the para-dimethylaminophenyl (1–5) and para-ethoxyphenyl (5) groups.

Diarylhalotelluronium(IV) cations [(8-Me2NC10H6)2TeX]+ (X = Cl, Br, I) stabilized by intramolecularly coordinating N-donor substituents

The stoichiometrically controlled halogenation of the intramolecularly coordinated diaryltelluride (8-Me2NC10H6)2Te using SO2Cl2, Br2 and I2 was studied. At an equimolar ratio, the diarylhalotelluronium cations [(8-Me2NC10H6)2TeX](+) (1, X = Cl; 2, X = Br; 3, X = I) formed and were isolated as 1·Cl(-)·H2O·1/2THF, 2·Br(-), and 3·I(-), respectively. When the same reactions were carried out in the presence of KPF6, 1·PF6(-) and 22·Br(-)·PF6(-) were obtained. The chlorination of (8-Me2NC10H6)2Te with an excess of SO2Cl2 occurred with a double electrophilic substitution at the 8-dimethylaminonaphthyl residues (in the ortho- and para-positions) and afforded the diaryltellurium dichloride (5,7-Cl2-8-Me2NC10H4)2TeCl2 (4). The bromination of (8-Me2NC10H6)2Te with three equivalents of Br2 took place with a single electrophilic substitution at the 8-dimethylaminonaphthyl residues (in the para-positions) and provided the diaryltellurium dibromide (5-Br-8-Me2NC10H5)2TeBr2 (5), while an excess of Br2 produced the diarylbromotelluronium cation [(5-Br-8-Me2NC10H5)2TeBr](+) (6) that was isolated as 6·Br3(-). The reaction of (8-Me2NC10H6)2Te with two or three equivalents of iodine provided 3·I3(-) and 3·I3(-)·I2, respectively. In the presence of water, 1·Cl(-)·H2O·1/2THF, 2·Br(-), 3·I(-) and 3·I3(-) hydrolyzed to give the previously known diarylhydroxytelluronium cation [(8-Me2NC10H6)2TeOH](+) (7) that was isolated as 7·Cl(-), 7·Br(-)·H2O·THF, 7·I(-) and 7·I3(-)·H2O, respectively. The molecular structures of 1-7 were investigated in the solid-state by (125)Te MAS NMR spectroscopy and X-ray crystallography and in solution by multinuclear NMR spectroscopy ((1)H, (13)C, (125)Te), electrospray mass spectrometry and conductivity measurements. The stabilization of cations 1-3 by the intramolecular coordination was estimated by DFT calculations at the B3PW91/TZ level of theory.