Biomedical subjects

Edward R T Tiekink

Publications and source records attributed to Edward R T Tiekink.

18 recordsLinked to original sources

PubMed2006

Luminescent phosphine gold(I) thiolates: correlation between crystal structure and photoluminescent properties in [R3PAu{SC(OMe)=NC6H4NO2-4}] (R = Et, Cy, Ph) and [(Ph2P-R-PPh2){AuSC(OMe)=NC6H4NO2-4}2] (R = CH2, (CH2)2, (CH2)3, (CH2)4, Fc).

X-ray crystallography shows the gold atoms in [R3PAu{SC(OMe)=NC6H4NO2-4}] (R = Et, Cy, Ph; 1-3, respectively) and [(Ph2P-R-PPh2){AuSC(OMe)=NC6H4NO2-4}(2)] (R = CH2, (CH2)2, (CH2)3, (CH2)4, Fc; 4-8, respectively) are linearly coordinated by phosphorus and thiolate-sulfur; weak intramolecular Au...O interactions are featured in all structures. The smaller ethyl substituents in 1 allow for supramolecular association via Au...S and Au...Au interactions that are not found in 2 and 3, which contain larger phosphorus-bound Cy and Ph groups, respectively. Intramolecular Au...Au interactions are found in the dppm, dppe, dppp, and Fc structures but not in the dppp analogue, for which an anti conformation was found. The structures have been correlated with the results from photophysical study conducted in the solid state. Thus, photoexcitation of 1-7 with lambda > 350 in the solid state and in solution produces green and blue luminescence, respectively. The spectra in each medium are remarkably similar to each other, and so the emission energy and excitation maxima observed for 1-7 appear to be independent of the nature of the ancillary phosphines, as well as the presence or absence of Au...Au interactions, either intermolecularly or intramolecularly.

Journal Article↗

PubMed2006

Osmium catalyzed dihydroxylation of 1,2-dioxines: a new entry for stereoselective sugar synthesis.

A series of 3,6-substituted 3,6-dihydro-1,2-dioxines were dihydroxylated with osmium tetroxide to furnish 1,2-dioxane-4,5-diols (peroxy diols) in yields ranging from 33% to 98% and with de values not less than 90%. The peroxy diols were then reduced to generate a stereospecific tetraol core with R,R,S,S or "allitol" stereochemistry. The peroxy diols and their acetonide derivatives were also ring-opened with Co(II) salen complexes to give novel hydroxy ketones in 77-100% yield, including the natural sugar psicose. Importantly, preliminary work on the catalytic asymmetric ring-opening of meso-peroxy diols using the Co(II) Jacobsens's catalyst indicates that asymmetric sugar synthesis from 1,2-dioxines is possible.

Journal Article↗

PubMed2006

pi-Acid/pi-base carbonyloxo, carbonylsulfido, and mixed-valence complexes of tungsten.

Carbonyloxotungsten(IV) complexes, TpWOX(CO), are produced in the reactions of dioxygen (for X = Cl, Br, I) or pyridine N-oxide [for X = S(2)P(OPr(i))(2), S(2)PPh(2)] with TpWX(CO)(2) [Tp = hydrotris(3,5-dimethylpyrazol-1-yl)borate]. Analogous carbonylsulfidotungsten(IV) species, TpWSX(CO), result from the reactions of TpWX(kappa(2)-MeCN)(CO) with propylene sulfide. The carbonyloxo complexes exhibit nu(CO) and nu(W=O) IR bands in the 1995-1965 and 957-951 cm(-1) regions, respectively; the nu(CO) and nu(W=S) bands of the carbonylsulfido species appear at 1970-1937 and 512-502 cm(-1), respectively. The complexes possess C(1) symmetry and display carbonyl (13)C NMR resonances at delta 272-287, with J(WC) 160-196 Hz. The crystal structures of TpWO(S(2)PPh(2))(CO) and TpWS(S(2)PPh(2))(CO).0.5CHCl(3) reveal distorted octahedral tungsten centers coordinated by a fac tridentate Tp ligand and mutually cis, monodentate chalcogenido [d(W=O) = 1.698(4) A; d(W=S) = 2.135(4) Angstroms], carbonyl, and dithiophosphinato ligands. In refluxing toluene, TpWOI(CO) converts into purple, mixed-valence TpW(III)I(CO)(mu-O)W(V)OITp. The dinuclear complex contains a nearly linear [173.1(6) degrees] mu-oxo bridge connecting disparate distorted octahedral tungsten centers. The metrical parameters and spectroscopic properties are consistent with the presence of a W(III)/W(V) mixed-valence species, possessing a filled, delocalized three-center (W-O-W) pi bond and a localized (on W(III)), filled d(pi) orbital that back-bonds to the carbonyl ligand.

Journal Article↗

PubMed2005

Synthesis, structural characterization, and computational studies of novel diiodine adducts with the heterocyclic thioamides N-methylbenzothiazole-2-thione and benzimidazole-2-thione: implications with the mechanism of action of antithyroid drugs.

Reaction of N-methylbenzothiazole-2-thione (C8H7NS2 or NMBZT) with diiodine produced the charge-transfer (ct) complex [(NMBZT).I2] (1). NMBZT reacts with diiodine in the presence of FeCl3 in a molar ratio of 3:6:1 and forms the ionic complex [[(NMBZT)2I+].[FeCl4]-] (2) together with [[(NMBZT)2I+].[I7]-] (2a) iodonium salt. The reaction of benzimidazole-2-thione (C7H6N2S or MBZIM) with diiodine on the other hand results in the formation of the ct [[(MBZIM)2I]+[I3]-].[(MBZIM).I2] (3) compound. The compounds have been characterized by elemental analyses, DTA-TG, FT-Raman, FT-IR, UV-vis, and 1H NMR spectroscopies, and X-ray crystal structure determinations. Compound 1, C8H7I2NS2, is orthorhombic with a space group Pna2(1) and a = 12.5147(13) angstroms, b = 22.536(3) angstroms, c = 4.2994(5) angstroms, and Z = 4. Compound 2, C16H14Cl4FeIN2S4, is monoclinic, space group C2/c, a = 35.781(2) angstroms, b = 7.4761(5) angstroms, c = 18.4677(12) angstroms, beta = 107.219(1) degrees, and Z = 8. Compound 3, C21H18I6N6S3, monoclinic, space group P2(1)/n, a = 14.0652(11) angstroms, b = 22.536(3) angstroms, c = 4.2994(5) angstroms, beta = 99.635(7) degrees, and Z = 4, consists of two component moieties cocrystallized, one neutral which contains the benzimidazole-2-thione (MBIZM) ligand bonded with an iodine atom through sulfur, forming a compound with a "spoke" structure [(MBZIM)I2] 3a, while the other is the ionic complex [[(MBZII)2I+].[I3]-] (3b). The X-ray crystal structure of 1 shows a bond between the thione-sulfur atom and one of the iodine atoms in an essentially planar arrangement. In the cation of 2, an iodine is coordinated by two thione-sulfur atoms in a linear arrangement but the molecule is not planar. For the first time in the solid state a spoke-ionic mixed complex has been characterized in 3. One component of the structure is a molecular diiodine adduct, i.e., [(MBZIM)I2] (3a), with a linear coordination geometry in a decidedly planar arrangement, and the other component is an ionic adduct [[(MBZIM)2I]+.[I3]-] (3b) with the cation having an arrangement similar to that found for 1. Theoretical calculations using density functional (DFT) and ab initio Hartree-Fock theory have been carried out for 1 and 3a,b. The results are consistent with the experimental data. Conclusions on the behavior of a thioamide, when used as an antithyroid drug, have also been made.

Antithyroid Agents↗

PubMed2005

Antiplasmodial activity of ferrocenyl chalcones: investigations into the role of ferrocene.

A series of ferrocenyl chalcones were synthesized and evaluated in vitro against Plasmodium falciparum (K1) in a [3H] hypoxanthine uptake assay. Appropriate size, electronic, lipophilic and electrochemical parameters were determined for QSAR analysis. The results showed that the location of ferrocene influenced the ease of oxidation of Fe2+ in ferrocene and the polarity of the carbonyl linkage. These parameters were found to influence antiplasmodial activity. A general trend was noted in which compounds with ferrocene adjacent to the carbonyl linkage (series A) were associated with more selective and potent antiplasmodial activities. These compounds had polarized carbonyl linkages, lower lipophilicities and ferrocene rings that were less readily oxidized. The most active analogue was 1-ferrocenyl-3-(4-nitrophenyl)prop-2-en-1-one (28) (IC50 4.6 microM, selectivity index 37 against KB3-1 cells). To understand how the redox properties of ferrocene might influence antiplasmodial activity, the oxidant properties of selected compounds were investigated in antioxidant (ABTS+) and EPR experiments. The incorporation of ferrocene in the chalcone template was found to enhance its role in processes that involved the quenching and generation of free radicals. Thus, ferrocene may participate in redox cycling and this process may contribute to the antiplasmodial activity of ferrocenyl chalcones. However, the extent to which this property is manifested is also influenced by other physicochemical properties (lipophilicity, polarity, and planarity) of the compound.

Animals↗

PubMed2005

1,2-dioxines containing tethered hydroxyl functionality as convenient precursors for pyran syntheses.

A new method for the construction of tetrahydropyrans derived from readily available 1,2-dioxines containing a tethered hydroxyl moiety is described. The reaction proceeds via a base-catalyzed rearrangement of the 1,2-dioxines to either the isomeric cis or trans gamma-hydroxy enones followed by intramolecular oxa-Michael addition of the tethered hydroxyl group.

Anticholesteremic Agents↗

PubMed2005

Formation of mono(dithiolene)-thiocarboxamido complexes in reactions of thio(dithiocarbamato)-Mo/W complexes and dimethyl acetylenedicarboxylate.

Reactions of TpMS(S(2)CNEt(2)) with dimethyl acetylenedicarboxylate in dichloromethane produce olive green/black TpM{S(2)C(2)(CO(2)Me)(2)}(SCNEt(2)-kappa(2)S,C) (M = Mo (1), W (2); Tp = hydrotris(3,5-dimethylpyrazol-1-yl)borate). The seven-coordinate complexes exhibit pseudo-octahedral (1) and distorted pentagonal bipyramidal (2) coordination spheres comprised of tridentate fac-Tp, bidentate dithiolene, and thiocarboxamido-kappa(2)S,C ligands. In the solid state, molecules of 1 exhibit pseudo-C(s)() symmetry, with the thiocarboxamide NEt(2) group in a cleft in the Tp ligand. Molecules of 2 have C(1) symmetry in the solid state; here, the thiocarboxamide unit is orientated along one of the W-S(dithiolene) bonds with its NEt(2) group projecting away from the Tp ligand. Both complexes possess effective C(s)() symmetry in solution. Reaction of TpMoI(CO)(3) with AgS(2)CNEt(2) affords olive green TpMo(S(2)CNEt(2))(CO)(2) (3), which reacts with propylene sulfide in a new synthesis for TpMoS(S(2)CNEt(2)), the starting material for 1. Complex 3 exhibits a distorted pentagonal bipyramidal structure, the axial sites being defined by a Tp nitrogen atom and a carbonyl ligand, the pentagonal plane by the remaining nitrogen and carbonyl donors and the two sulfur atoms of the bidentate dithiocarbamate ligand.

Journal Article↗

PubMed2004

A domino ring-opening/epoxidation of 1,2-dioxines.

When allowed to react with alkaline hydrogen peroxide, monocyclic 1,2-dioxines ring-open to their isomeric gamma-hydroxyenone intermediates which are rapidly epoxidized to afford trans-4-hydroxy-2,3-epoxyketones in 21-81% yield. In the case of meso-1,2-dioxines, Co(II) complex catalyzed asymmetric ring-opening of the 1,2-dioxine may be employed to furnish enantioenriched epoxides

Journal Article↗

PubMed2004

Novel endoperoxide antimalarials: synthesis, heme binding, and antimalarial activity.

We report the synthesis of a series of novel epoxy endoperoxide compounds that can be prepared in high yields in one to three steps from simple starting materials. Some of these compounds inhibit the growth of Plasmodium falciparum in vitro. Structure-activity studies indicate that an endoperoxide ring bisubstituted with saturated cyclic moieties is the pharmacophore. To study the molecular basis of the action of these novel antimalarial compounds, we examined their ability to interact with oxidized and reduced forms of heme. Some of the compounds interact with oxidized heme in a fashion similar to chloroquine and other 4-aminoquinolines, while some of the compounds interact with reduced heme. However, the level of antimalarial potency is not well correlated with these activities, suggesting that some of the endoperoxides may exert their antimalarial activities by a novel mechanism of action.

Animals↗

PubMed2003

Redox interplay of oxo-thio-tungsten centers with sulfur-donor co-ligands.

The oxo-thio-W(VI) complexes TpWOS(S(2)PR(2)-S) and TpWOS(pyS-S) (Tp = hydrotris(3,5-dimethylpyrazol-1-yl)borate, R = OEt, Ph; pyS = pyridine-2-thiolate) have been prepared and characterized by microanalytical, spectroscopic, and structural techniques. Crystals of the 1,2-dichloroethane hemisolvate of TpWOS(S(2)PPh(2)-S) belong to the triclinic space group Ponemacr; with a = 10.732(6) A, b = 16.91(1) A, c = 10.021(4) A, alpha = 104.40(4) degrees, beta = 107.52(3) degrees, gamma = 96.09(5) degrees, V = 1647(1) A(3) for Z = 2. The complex exhibits a distorted octahedral structure featuring a facial tridentate Tp ligand and mutually cis terminal oxo (W-O(1) = 1.712(7) A), terminal thio (W-S(1) = 2.162(3) A), and monodentate dithiophosphinate ligands. X-ray absorption and extended X-ray absorption fine structure results support a related oxo-thio formulation for TpWOS(pyS-S). The complexes are reduced to the corresponding oxo-thio-W(V) anions, [TpWOS(S(2)PR(2)-S)](-) and [TpWOS(pyS-S)](-), which exhibit highly anisotropic EPR spectra. They are oxidized to form the EPR-active (dithio)oxo-W(V) cations, [TpWO(S(3)PR(2)-S,S')](+) and [TpWO(pyS(2)-N,S)](+) (pyS(2) = pyridine-2-dithio). Green [TpWO(pyS(2)-N,S)]BF(4), formed in the reaction of TpWOS(pyS) and NOBF(4), has been isolated and spectroscopically and structurally characterized. Crystals of [TpWO(pyS(2)-N,S)]BF(4) belong to the monoclinic space group Cc with a = 16.007(5) A, b = 14.091(4) A, c = 13.608(4) A, beta = 124.525(4) degrees, V = 2528.8(13) A(3) for Z = 4. The cation exhibits a distorted octahedral structure featuring facial tridentate Tp, terminal oxo (W-O(1) = 1.632(12) A), and bidentate pyridine-2-dithio-N,S (W-S(1) = 2.317(7) A, S(1)-S(2) = 2.037(9) A) ligands. The structures and redox behavior of the complexes are compared and contrasted with those of the related molybdenum complexes, TpMo(VI)OS(S(2)PR(2)-S) and TpMo(IV)O(pyS(2)-N,S) (Hill, J. P.; Laughlin, L. J.; Gable, R. W.; Young, C. G. Inorg. Chem. 1996, 35, 3447).

Crystallography, X-Ray↗

PubMed2003

Binuclear copper(II) complexes of xylyl-bridged bis(1,4,7-triazacyclononane) ligands.

Copper(II) complexes of three bis(tacn) ligands, [Cu(2)(T(2)-o-X)Cl(4)] (1), [Cu(2)(T(2)-m-X)(H(2)O)(4)](ClO(4))(4).H(2)O.NaClO(4) (2), and [Cu(2)(T(2)-p-X)Cl(4)] (3), were prepared by reacting a Cu(II) salt and L.6HCl (2:1 ratio) in neutral aqueous solution [T(2)-o-X = 1,2-bis(1,4,7-triazacyclonon-1-ylmethyl)benzene; T(2)-m-X = 1,3-bis(1,4,7-triazacyclonon-1-ylmethyl)benzene; T(2)-p-X = 1,4-bis(1,4,7-triazacyclonon-1-ylmethyl)benzene]. Crystals of [Cu(2)(T(2)-m-X)(NPP)(mu-OH)](ClO(4)).H(2)O (4) formed at pH = 7.4 in a solution containing 2 and disodium 4-nitrophenyl phosphate (Na(2)NPP). The binuclear complexes [Cu(2)(T(2)-o-XAc(2))(H(2)O)(2)](ClO(4))(2).4H(2)O (5) and [Cu(2)(T(2)-m-XAc(2))(H(2)O)(2)](ClO(4))(2).4H(2)O (6) were obtained on addition of Cu(ClO(4))(2).6H(2)O to aqueous solutions of the bis(tetradentate) ligands T(2)-o-XAc(2) (1,2-bis((4-(carboxymethyl)-1,4,7-triazacyclonon-1-yl)methyl)benzene and T(2)-m-XAc(2) (1,3-bis((4-(carboxymethyl)-1,4,7-triazacyclonon-1-yl)methyl)benzene), respectively. In the binuclear complex, 3, three N donors from one macrocycle and two chlorides occupy the distorted square pyramidal Cu(II) coordination sphere. The complex features a long Cu...Cu separation (11.81 A) and intermolecular interactions that give rise to weak intermolecular antiferromagnetic coupling between Cu(II) centers. Complex 4 contains binuclear cations with a single hydroxo and p-nitrophenyl phosphate bridging two Cu(II) centers (Cu...Cu = 3.565(2) A). Magnetic susceptibility studies indicated the presence of strong antiferromagnetic interactions between the metal centers (J = -275 cm(-1)). Measurements of the rate of BNPP (bis(p-nitrophenyl) phosphate) hydrolysis by a number of these metal complexes revealed the greatest rate of cleavage for [Cu(2)(T(2)-o-X)(OH(2))(4)](4+) (k = 5 x 10(-6) s(-1) at pH = 7.4 and T = 50 degrees C). Notably, the mononuclear [Cu(Me(3)tacn)(OH(2))(2)](2+) complex induces a much faster rate of cleavage (k = 6 x 10(-5) s(-1) under the same conditions).

Journal Article↗

PubMed2003

Base- and Co(II)-catalyzed ring-opening reactions of perhydrooxireno[2,3-d][1,2]dioxines: an efficient route to 4-hydroxy-2,3-epoxy-ketones.

A series of 3,4,6-substituted 3,6-dihydro-1,2-dioxines were epoxidized with m-chloroperbenzoic acid to furnish perhydrooxireno[2,3-d][1,2]dioxines (epoxy-1,2-dioxines) in yields ranging from 51% to 93% with de's from 26% to 100%. Unsymmetrical epoxy-1,2-dioxines were ring-opened using triethylamine to yield 4-hydroxy-2,3-epoxy-ketones quantitatively, and meso-epoxy-1,2-dioxines were ring-opened using Co(II) salen complexes to afford 4-hydroxy-2,3-epoxy-ketones in 77-98% yield. The first reported examples of the catalytic asymmetric ring-opening of meso-epoxy-1,2-dioxines using a range of chiral Co(II) salen and beta-ketoiminato complexes to afford highly enantio-enriched 4-hydroxy-2,3-epoxy-ketones are also presented.

Journal Article↗

PubMed2003

A novel synthesis of functionalized tetrahydrofurans by an Oxa-Michael/Michael cyclization of gamma-hydroxyenones.

An approach to highly functionalized tetrahydrofuran derivatives based upon a novel Oxa-Michael/Michael dimerization of cis-gamma-hydroxyenones is presented. The reaction begins with either 1,2-dioxines or trans-gamma-hydroxyenones and proceeds by addition of one molecule of trans-gamma-hydroxyenone to another molecule of cis- or trans-gamma-hydroxyenone catalyzed by an alkoxide or hydroxide base. Subsequent intramolecular Michael addition of the keto-enolate gives the observed tetrahydrofurans. Substitution at both the 2- and 4-positions of the gamma-hydroxyenone is tolerated; however, for 4-substituted gamma-hydroxyenones, selectivity issues arise due to the possibility of heterochiral or homochiral dimerizations. The major products were those with all contiguous groups trans.

Journal Article↗

PubMed2003

Cationic sigma-phenylplatinum(II) complexes with carboxylic acid functionality: pK(a) determinations and x-ray structures.

The preparation and characterization of a novel series of cationic sigma-phenylplatinum(II) complexes of the type trans-[Pt(sigma-C(6)H(5))(L)(2)A]OTf (A = picolinic acid, L = PPh(3) (4) and PMePh(2) (7); A = nicotinic acid, L = PPh(3) (5) and PMePh(2) (8); A = isonicotinic acid, L = PPh(3) (6), PMePh(2) (9), and PEt(3) (10)) are described. The pK(a) value for the carboxylic acid functionality in selected complexes was found to follow the order 7 (pK(a) = 5.23 +/- 0.09) > 8 (4.85 +/- 0.10) > 9 (3.51 +/- 0.08) > 6 (3.26 +/- 0.07) approximately 10 (3.21 +/- 0.08) by means of potentiometric titration experiments in 50% (v/v) EtOH/H(2)O solution at 295 K. The X-ray crystal structures of 9 and 10 were also determined. The asymmetric unit of each of 9 and 10 comprises a univalent complex cation, a triflate anion, and a solvent CH(2)Cl(2) molecule of crystallization. Centrosymmetrically related pairs of complex cations in 9 associate via the familiar carboxylic acid dimer motif, whereas with 10, the carboxylic acid dimer motif is absent. Instead, the carboxylic acid residue forms both donor and acceptor interactions to the triflate anion and CH(2)Cl(2) solvent of crystallization, respectively, to afford a 10-membered ring structure. Possible reasons for the observed differences in the solid-state structures of 9 and 10 are presented.

Journal Article↗

PubMed2002

1,2-dioxines as masked cis gamma-hydroxy enones and their versatility in the synthesis of highly substituted gamma-lactones.

Addition of highly stabilized ester nucleophiles to 1,2-dioxines affords good to high yields of gamma-lactones with high diastereoselectivity. Heterolytic or homolytic cleavage of the 1,2-dioxines under appropriate conditions generates the key reactive cis gamma-hydroxy enones, which ultimately afford the observed gamma-lactones. Diastereoselectivity is installed as a result of anti 1,4-addition by the ester enolate to the cis enones followed by intramolecular cyclization. The reaction is tolerant of a range of substitution patterns on the 1,2-dioxine while a broad range of esters are also accommodated. In addition to the synthesis of racemic gamma-lactones, highly enantioenriched gamma-lactones can also be synthesized when chiral cobalt(II) catalysts are employed for the initial homolytic ring-opening of the 1,2-dioxine.

Journal Article↗

PubMed2002

An anionic C(3)-C(5) ring expansion of beta-ketocyclopropanes to cyclopentenols.

[reaction: see text] When treated with base, beta-ketocyclopropylcarboxylates ring-open to initially afford either cis or trans alpha,beta-unsaturated ketones. The cis isomer undergoes an intramolecular aldol reaction to afford allylic cyclopentenols in high yield and excellent diastereoselectivity. Choice of base is key to a successful outcome.

Journal Article↗

PubMed2002

Gold derivatives for the treatment of cancer.

The cytotoxicity and anti-tumour activity screening trials for both gold(I) and gold(III) are summarised. Gold(I) thiolates employed clinically in the treatment of rheumatoid arthritis display some potency against various tumours but a greater potential is found in their analogues. In particular, analogues featuring a linear P-Au-S arrangement in which the thiolate ligand is derived from a biologically active thiol display high potency. Further, targeting mitochondria with tetrahedrally coordinated gold(I) phosphine compounds with enhanced hydrophilicity is a research direction with exciting potential. Recent research has shown that gold(III) compounds featuring square-planar geometries, as found in cisplatin, may target DNA and may provide new anti-tumour agents.

Animals↗

PubMed2002

Antimony and bismuth compounds in oncology.

The main group elements antimony and bismuth are used clinically, primarily for the treatment of Leishmaniasis (antimony) and ulcers (bismuth). Despite their medicinal efficacy, the exploration of the anti-cancer potential of antimony and bismuth compounds is not as well developed as for other metal-containing species. The results of cytotoxicity and anti-tumour screening for antimony(III), antimony(V) and bismuth(III) compounds are summarised in this review. While this is a relatively undeveloped field of research endeavour, promising anti-tumour activity has been reported, in particular for bismuth compounds.

Animals↗