Generation and biomimetic chemistry of tungsten-dithiolene complexes containing the hydrotris(3,5-dimethylpyrazol-1-yl)borate ligand.

Reactions of bis(thio)-W(VI) complexes, LWS2X (L = hydrotris (3,5-dimethylpyrazol-1-yl)borate, X = monoanion), with alkynes produce dithiolene complexes, LWX(dithiolene). The synthesis and characterization of orange LW(OPh){S2C2(CO2Me)2} (1) and burgundyred LW(SePh) {S2C2(Ph)(2-quinoxalinyl)} (2) and the X-ray crystal structure of 1.0.5CH2Cl2, are described in detail. Crystals of 1.0.5CH2Cl2 are orthorhombic, space group Pbcn, with a = 29.826(6), b = 13.291(4), c = 16.078(4) A, V = 6373(5) A3, and Z = 8. The six-coordinate, distorted-octahedral complex features a tridentate L ligand, a monodentate phenoxide ligand, and a bidentate dithiolene ligand. The short W-S bonds (2.267(4) and 2.279(4) A) and the parameters associated with the phenoxide ligand (W-O = 1.850(8) A, W-O-C = 146(1) degree), point to a considerable degree of W-ligand multiple bonding in the [W(OPh)(dithiolene)]+ unit. For 2, W-Se and average W-S distances of 2.49(2) A and 2.30(2) A, respectively, have been obtained from EXAFS studies. The formation of yellow 3,3'-dithiobis[2-(phenyl)thieno[2,3-b]quinoxaline] (3) upon oxidation of 2 supports the likely generation of urothione upon oxidative degradation of molybdopterin-containing tungsten enzymes from hyperthermophilic organisms.

Zinc, cadmium, and mercury complexes of 5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine (dmtp). Preparation, spectroscopic characterization, and biological activity. X-ray crystal structures of [Zn(dmtp)2Br2], [Hg(dmtp)2Cl2], and [Hdmtp]2[CdBr4]. 2H2O.

The preparation and spectroscopic characterization of a series of dmtp complexes of Zn, Cd, and Hg, where dmtp is 5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine, is reported. Crystal structure analyses of [Zn(dmtp)2Br2] and [Hg(dmtp)2Cl2] reveal distorted tetrahedral geometries about the central atoms and the dmtp ligands to coordinate via the N(3) atom exclusively. In the X-ray structure of [Hdmtp]2[CdBr4].2H2O, the [Hdmtp]+ cation is protonated at the N(3) atom, there being no significant interaction between Hdmtp and cadmium. A study of the antimicrobial activity of the complexes shows that the [Cd(dmtp)X2(OH2)] (X = Cl, Br) compounds display activity against two strains.

Anti-cancer potential of gold complexes.

A full range of gold compounds is currently being investigated for their potential as anti-tumor agents. Gold(I) compounds related to the anti-arthritic drug continue to attract attention, especially those carrying biologically active molecules with anti-tumor activity in their own right. Tetrahedrally coordinated gold(I) compounds, that possibly target mitochondria, are under development with a particular focus upon moderating their hydrophilicity. A resurgence of interest in square-planar gold(III) compounds has occurred in the last decade. A wide variety of species: mono- and di-nuclear, neutral and charged, coordination and organometallic, etc. are being developed. Supporting many investigations are studies of mechanistic aspects of gold compounds but a clear understanding of the mechanism of action of these compounds has yet to be delineated.

Colloidal metallic gold is not bio-inert.

Metallic gold (Au degrees ) is a likely biotransformation product of monovalent gold, Au(I) whenever it is dissociated from in vivo ligands, Au degrees being formed either by bioreduction or by spontaneous dismutation (with co-production of trivalent gold). This review discusses the preparation and some biologically relevant properties of colloidal metallic gold (CMG) in its nano-particulate form. Tyndall's purple, a well characterised preparation of CMG, shows potent anti-arthritic activity in rats, approximately 10(3) times that of sodium aurothiomalate (Myocrysin). Even more remarkable is its broader spectrum of action in rats compared to this classic DMARD.

A Study of the Antitumour Activity of Four Triorganophosphinegold(I) Thiolates: R(3) PAu(SR'), R = Ph, Cy, Et; SR'H = 6-Mercaptopurine and R = Et; SR'H = 6-Thioguanine.

The antitumour activities of four triorganophosphinegold(I) thiolates, R(2)PAu(S'R) [R = Ph, Cy, Et; SR'H = 6-mercaptopurine and R Et; SR'H = 6-thioguanine] against the National Cancer Institute (NCI) panel of 60 cell lines are reported The [Cy(3)PAu(6-MP)] complex proved to be the more cytotoxic of the four complexes tested. For the 6-MP series, an order of cytotoxicity was established such that the activity followed the order R = Cy > Ph > Et. Sub-panel selectivity against the Leukemia cell lines was found for each of [Cy(3) PAu(6-MP)] and [Et(3)PAu(6-TG)].

Photochemical N-demethylation of alkaloids.

Certain alkaloids were observed to undergo N-demethylation processes under photochemical conditions. Tropine, acetyltropine, tropinone, and atropine were cleanly N-demethylated upon treatment with tetraphenylporphin, oxygen, and light. Dextromethorphan also underwent a N-demethylation reaction, but reacted further to afford an imine. In contrast, 14-acyloxycodeinones underwent a photochemically induced tandem N-demethylation acyl migration.

(Benzoxazole-2-thiolato-S)(benzoxazole-2-thione-S)bis(triphenylphosph ine)copper(I).

The Cu atom in [Cu(C(7)H(4)NOS)(C(7)H(5)NOS)(C(18)H(15)P)(2)] is tetrahedrally coordinated by a P(2)S(2) donor set. One S atom is derived from neutral benzoxazole-2-thione and the other from the deprotonated form of the ligand. The two sulfur ligands are connected via an N-H.N interaction, leading to the formation of an eight-membered ring.

Bis[N-phenyl(dicyclohexylthiophosphinoyl)thiomethanamido-S, S']copper(II).

The ligands in [Cu(C(19)H(27)NPS(2))(2)] adopt an S,S'-chelation mode leading to an S(4) donor set which defines a square-planar geometry about the Cu atom, which lies on an inversion centre.

Characterisation and in vitro cytotoxicity of triorganophosphinegold(i) 2-mercaptobenzoate complexes.

The preparation and full NMR ((1)H, (13)C and (31)P) characterisation of three [R(3)PAu(2mba)] complexes, Where R = Et, Ph and Cy, and 2mba is the anion derived from 2-mercaptobenzoic acid is reported. An interesting solvent dependence in the (1)H spectra is rationalised in terms of competing intra- and inter-molecular hydrogen bonding. An X-ray analysis of the [Ph(3) PAu(2mba)] species reveals a linear P-Au-S arrangement and association in the lattice via the familar carboxylic acid dimer motif. The in Vitro cytotoxicity against seven human tumout lines is also described. The complexes display moderate to very high activity. Particularly noteworthy is their greater activity against the H226 cell line (non-small cell lung cancer) compared with that displayed by a range of cytotoxic drugs.

Synthesis, Characterisation and Anti-Fungal Activities of Some New Copper(II) Complexes of Octamethyl Tetraaza-Cyclotetradecadiene.

The ligand Me(8)[14]diene, L, in its free state as well as in the dihydroperchlorate form, L.2HClO(4), coordinates copper(ll) in different salts to yield a series of [CuLX(x)] X(y)(H(2)O)(z) complexes where X = NO(3), ClO(4), NCS, Cl and Br; x and y may have values of 0 or 2 and z = 0, 1 or 2. The complex, [CuL(ClO(4))(2)].2H(2)O is found to undergo axial ligand substitution reactions with SCN(-), NO(3) and Cl(-) to give a variety of substitution derivatives: [CuL(ClO(4))(m) X(n)] where X = NCS, NO(3) and Cl; m = 0 or 1, and n = 1 or 2. The complexes .have been characterised on the basis of analytical, spectroscopic, magnetic and conductance data. The anti-fungal activities of the ligand and its complexes have been investigated against a range of phytopathogenic fungi.

Anti-arthritic activity in rats of some phosphinegold(i) thionucleobases and related thiolates.

A number of phosphinegold(I) thiolates where, generally, the thiolate is derived from a thionucleobase, have been screened for anti-arthritic activity in Dark Agouti rats, a gold sensitive model for arthritis. Potency and toxicity data showed that, generally, the Ph(3)P derivatives and species based on thiopurines were the most effective and that with other complexes enhanced activity was accompanied by greater toxicity.

In vitro antitumour activity of some triorganophosphinegold(i) thionucleobases.

A series of phosphinegold(I) thionucleobase analogues, [R(3)PAu(SR(x))] (R = Et, Ph or chexyl; HSR(1) = 2-mercaptobenzoic acid, HSR(2) = 2-thiouracil, HSR(3) = 6-mercaptopurine and HSR(4) = 6-thioguanine) have been examined for their in vitro cytotoxicity in L1210 murine leukemia cells in culture. The range of ID(50) values (continuous 48 h exposure) for the complexes is 0.041 - 0.131 muM. The complexes with SR(3) and SR(3) are generally the most active; however, there is no clear trend associated with the phosphine ligands.

Synthesis, characterization, and electrochemistry of cis-oxothio- and cis-bis(thio)tungsten(VI) complexes of hydrotris(3,5-dimethylpyrazol-1-yl)borate.

The complexes TpWO2X react with sulfiding agents such as B2S3 or P4S10 to give the oxothio- and bis(thio)tungsten(VI) complexes TpWOSX (X = Cl(-)) and TpWS2X [X = Cl(-), S2PPh2(-); Tp = hydrotris(3,5-dimethylpyrazol-1-yl)borate]. The reaction of TpWS2Cl with (i) PPh3 in pyridine and (ii) dimethyl sulfoxide affords TpWOSCl in good overall yield. The chloro complexes undergo metathesis with alkali metal salts to yield species of the type TpWOSX and TpWS2X [X = OPh(-), SPh(-), SePh(-), (-)-mentholate]. The diamagnetic complexes exhibit NMR spectra indicative of C(1) (TpWOSX) or C(s) (TpWS2X) symmetry and IR spectra consistent with terminal oxo and thio ligation (nu(W=O), 940-925 cm(-1); nu(W=S) or nu(WS2), 495-475 cm(-1)). Crystals of (R,S)-TpWOS[(-)-mentholate] are monoclinic, space group P2(1), with a = 11.983(2) A, b = 18.100(3) A, c = 13.859(3) A, beta = 91.60(2) degrees, V = 3004.6(8) A(3), and Z = 4. Crystals of TpWS2(OPh)-CH2Cl2 are orthorhombic, space group Pbca, with a = 16.961(4) A, b = 33.098(7) A, c = 9.555(2) A, V = 5364(2) A(3), and Z = 8. The mononuclear, distorted-octahedral tungsten centers are coordinated by a tridentate Tp ligand, an alkoxy or aryloxy ligand, and two terminal chalcogenide ligands. The average W=O and W=S distances are 1.726(7) and 2.125(2) A, respectively, and the O=W=S and S=W=S angles 102.9(3) and 102.9(1) degrees, respectively. The tungsten and sulfur X-ray absorption spectra of TpWOSCl and TpWS2Cl are consistent with the presence of terminal pi-bonded thio ligands in both complexes. The thio complexes generally undergo a reversible one-electron reduction at potentials significantly more positive than their oxo analogues. The chemical, spectroscopic, and electrochemical properties of the complexes are heavily influenced by the presence of W=S pi frontier orbitals.

Anti-tumor activity, in vitro and in vivo, of some triphenylphosphinegold(i) thionucleobases.

The [Ph(3)PAu(6-MP)] complex, where 6-MPH is 6-mercaptopurine, is active against the cisplatinresistant cell line, mouse leukaemia L1210/DDP, as is the precursor compound [Ph(3)PAuCl], suggesting that the thiolate is not critical for activity. Against the human cell lines, FaDu (squamous cell carcinoma) and SKOV-3 (ovarian carcinoma), both [Ph(3)PAu(6-MP)] and [Ph(3)PAu(6-TG)], where 6-TGH is 6-thioguanine, were active. [Ph(3)PAu(6-MP)] was active against a murine PC6 plasmacytoma, but not as active as cisplatin.

Triphenyltin ortho-aminophenyl- and 2-pyridyl-thiolates: synthesis and in vitro antitumour activity.

The synthesis, spectroscopic characterization and in vitro antitumour activity of two triorganotin compounds, triphenyltin ortho-aminophenylthiolate (1) and triphenyltin 2-pyridylthiolate, compound (2) are reported. The structure of 1 is confirmed by X-ray diffraction, with the tin atom in a distorted tetrahedral geometry because of monodentate coordination, as a thiolate (Sn-S 2.431(2) A), of the ortho-aminophenylthiolate ligand. The in vitro antitumour activities of 1 and 2, against a number of cell lines, are comparable to those exhibited by methotrexate and doxorubicin, and higher than those of carboplatin and cisplatin.

Preparation and Anti-Tumour Activity of Some Arylbismuth(III) Oxine Complexes.

New arylbismuth(lll) oxinates, PhBi(MeOx)(2), (p-MeC(6)H(4))Bi(Ox)(2), (p-MeC(6)H(4))Bi(MeOx)(2), (p-ClC(6)H(4))Bi(Ox)(2), and (p-ClC(6)H(4))Bi(MeOx)(2) (Ox(-) = quinolin-8-olate and MeOx(-)=2-methylquinolin-8-olate) have been prepared by reaction of the appropriate diarylbismuth chlorides with Na(Ox) or Na(MeOx) in the presence of 15-crown-5. An X-ray crystallographic study has shown PhBi(MeOx)(2) to be a five coordinate monomer with distorted square pyramidal stereochemistry. Chelating MeOx ligands have a cisoid arrangement in the square plane and the phenyl group is apical. The lattice is stabilised by significant pi-pi interactions between centrosymmetric molecules. A range of these complexes has been shown to have high in vitro biological activity (comparable with or better than cisplatin) against L1210 leukaemia, the corresponding cisplatin resistant line, and a human ovarian cell line, SKOV-3. However, initial in vivo testing against a solid mouse plasmacytoma (PC6) and P388 leukaemia has not revealed significant activity.

Cytotoxicity of triorganophosphinegold(i) complexes of thiobenzoate.

The preparation and characterization of two triorganophosphinegold(I) complexes containing the anion derived from thiobenzoic acid are described. The cytotoxicity of these complexes has been investigated along with that of triphenylphosphinegold(I) mercaptopurinate, a known anti-tumor compound, against a variety of human cell lines. The complexes showed moderate to high cytotoxicity (ID(50) 250 - 2500 ng/ml).

Mechanistic investigations on the reaction between 1,2-dioxines and bulky stabilized phosphorus ylides: an efficient route to closely related cyclopropane stereoisomers.

The bulky stabilized ylides (2a-d) react with a range of 1,2-dioxines (1a-d) to afford the diversely functionalized cyclopropanes 7 in excellent yield and diastereomeric excess. This is in direct contrast to the situation when nonbulky ester ylides are utilized which results in a completely different cyclopropyl series. Through a combination of isolation, spectroscopic, temperature, and deuterium and additive effects studies, the mechanism of cyclopropane formation from this second pathway can be proposed. Importantly, enolate quenching of the intermediate 1-2lambda(5)-oxaphospholanes 4 prior to collapse results in an equilibrium mixture of intermediates 10 and 11 which have been fully characterized, and their formation is primarily a result of the steric bulk of the stabilized ester ylide. These intermediates (10/11) then collapse further and result in formation of the observed closely related cyclopropyl stereoisomers 7 and 8. Moreover, the addition of LiBr to these reactions allows for the control of which of the two possible cyclopropanation pathways will be dominant. Finally, optimal protocols that demonstrate the potential of this new cyclopropanation methodology for the ready construction of closely related cyclopropyl stereoisomers are presented.

X-Ray Structure and In Vitro Anti-Tumoural Activity of the Dimeric Bis[(2-Phenyl-1,2-Dicarba-Closo-Dodecaborane-1-Carboxylato)-Di-n-Butyltin] Oxide.

X-ray diffraction studies reveal the structure of {[(2-C(6)H(5)-1,2-C(2)B(10)H(10)-1-COO)Bu(2)Sn](2)O}(2), 1, to conform to the common motif found for {[(R'COO)R(2)Sn](2)O}(2) compounds. The dimer features a central Bu(2)Sn(2)O(2) unit (two-fold symmetry) with the two Bu(2)Sn groups being linked via bridging oxygen atoms, each of which also carries an exocyclic Bu(2)Sn moiety. The two pairs of exo- and endo-cyclic tin atoms are each linked via an almost symmetrically bridging carboxylate ligand and the two remaining ligands coordinate an exocyclic tin atom only, in the monodentate mode. The in vitro anti-tumour activity of 1, determined against a variety of cell lines, is compared with those of the corresponding 2-methylcarboranylacetate, derivative 2, and with clinically used compounds.

Synthesis, Characterisation and Antifungal Activities of Some New Copper(II) Complexes of Isomeric 3,5,7,7,10,12,14,14-Octamethyl-1,4,8,11-Tetraazacyclotetradecanes.

Three isomeric Me(8)[14]anes, L(A), L(B) and L(C), undergo complexation with copper(II) salts to form a series of [CuLX(n)(H(2)O)(x)]X(y).(H(2)O)(z) complexes where L = L(A), L(B) and L(C); X = Cl, Br, NO(3); n, x, y and z may have values of 0, 1 or 2. The complexes have been characterised on the basis of analytical, spectroscopic, magnetic and conductance data. Further, the X-ray crystal structure of one complex, [CuL(B)(OH(2))(2)](NO(3))(2), has been determined. The antifungal activity of all three isomeric ligands and their complexes has been investigated against a range of phytopathogenic fungi.