Isamu Kinoshita

In Vitro Heavy-Atom Effect of Palladium(II) and Platinum(II) Complexes of Pyrrolidine-Fused Chlorin in Photodynamic Therapy

Introduction of a heavy atom into photosensitizers generally facilitates intersystem crossing and improves the quantum yield (Phi(Delta)) of singlet oxygen ((1)O(2)), which is a key species in photodynamic therapy (PDT). However, little information is available about the physiological importance of this heavy-atom effect. The aim of this study is to examine the heavy-atom effect in simple metallochlorins in vitro at the cellular level. 1,3-Dipolar cycloaddition of azomethine ylide to 5,10,15,20-tetrakis(pentafluorophenyl)porphyrinato palladium(II) and platinum(II) afforded metallochlorins 4b and 4c in yields of 17.1 and 12.9%, respectively. The Phi(Delta) values increased in the order of 4a (0.28) < 4b (0.89) < 4c (0.92) in C(6)D(6). The photocytotoxicity of 4a, 4b, and 4c was evaluated in HeLa cells at a light dose of 16 J x cm(-2) with lambda > 500 nm and increased in the order of 4a < 4b < 4c at the concentration of 0.5 microM. The photocytotoxicity of 4b and 4c was significantly inhibited by addition of sodium azide, but not D-mannitol, suggesting that (1)O(2) is the major species causing cell death. Our results clearly indicate that 4b and 4c act as efficient (1)O(2) generators due to the heavy-atom effect in a cellular microenvironment as well as in nonphysiological media.

Design and synthesis of copper complexes of novel ligands based on the pyridine thiolate group

The versatile coordination properties of 2,2′-dipyridyldisulfide (dpds) enables a series of different copper complexes to be isolated in good yield, including [CuCl2(μ-dpds)] (1) which has a one-dimensional helical structure and [Cu(μ-Cl)(μ-dpds)] (4) which has a two-dimensional sheet structure. Flexible movement of the disulfide group in the dpds ligand facilitates the formation of complexes with a diverse range of structures. Compound 1 transforms into 4 almost quantitatively on standing in contact with methanol. After prolonged standing 4 slowly converts to the stable, betain-containing product, [Cu(μ-1-(2-pyridine)pyridiniumthiolato)(μ-Cl)] (8) with the concomitant production of elemental sulfur. The bromide congener of 4 undergoes the same transformation. The free ligand, 1-(2-pyridine)pyridiniumthiolate, can be released from 8 by treatment with CN−. On treatment of bis(2-pyridylthio)methane (BPTM) with CuCl2 [CuCl2(BPTM)]n (9) is formed. This complex has an infinite helical chain structure. Reaction between tris(2-pyridylthio)methane (TPTMH) and CuBr gave [CuBr(TPTM)] (12) and with [Cu(NCCH3)4]PF6 in the presence of oxygen, the complex [Cu(CH3CN)(TPTM)]PF6 (14) is formed. Complex 14 is the first structurally characterised example of a complex containing a Cu(II)–C(sp3) bond.

Unprecedented sugar-dependent in vivo antitumor activity of carbohydrate-pendant cis-diamminedichloroplatinum(II) complexes.

Eight carbohydrate-pendant platinum(II) complexes have been synthesized from carbohydrate-diamine conjugates. D-Glucose, D-mannose, D-galactose, D-xylose, and L-glucose are attached to the dichloroplatinum(II) moiety by 1,3- or 1,2-diaminopropane chelates through with an O-glycoside bond. All the carbohydrate moieties reduced the toxicity inherent with platinum(II) complexes.

Copper(II) complexes with tripodal imidazole-containing ligands. Structure-electrochemistry relationship

Mono- and dimeric copper(II) complexes of tris- (benzimidazol-2-ylmethyl)amine (L1) and of its derivatives with the imidazole NH protons substituted by a methyl (L2), ethyl (L3), benzyl (L4) or o-methylbenzyl (L5) group were prepared and characterized based on magnetic susceptibility, conductivity, cyclic voltammetric half-wave potential (E12), infrared, electronic and ESR spectra. The complexes containing H2O, NO3−, Cl−, Br−, N3−, and N-methylimidazole with L1–L5 were mononuclear copper(II) complexes, while the complexes with NCS− or NCO− and L1–L3 [except [Cu(L1)NCS](NO3)] were dinuclear ones, which dissociate to monomeric complexes in DMF solution. The E12 values of copper(II) in a series of complexes containing H2O or NO3− decrease in the order L5 > L1 > L2 > L3 > L4, whereas those in complexes with Br− and N-methylimidazole decrease in the orders L4 ≳ L5 > L1 > L2 > L3 and L5 > L1 > L4 ≳ L2 > L3, respectively. The relationship between the structure of the complexes and the E12 values are discussed in some detail.

Anion-Controlled Assembly of Four Manganese Ions: Structural, Magnetic, and Electrochemical Properties of Tetramanganese Complexes Stabilized by Xanthene-Bridged Schiff Base Ligands

The reaction of manganese(II) acetate with a xanthene-bridged bis[3-(salicylideneamino)-1-propanol] ligand, H(4)L, afforded the tetramanganese(II,II,III,III) complex [Mn(4)(L)(2)(μ-OAc)(2)], which has an incomplete double-cubane structure. The corresponding reaction using manganese(II) chloride in the presence of a base gave the tetramanganese(III,III,III,III) complex [Mn(4)(L)(2)Cl(3)(μ(4)-Cl)(OH(2))], in which four Mn ions are bridged by a Cl(-) ion. A pair of L ligands has a propensity to incorporate four Mn ions, the arrangement and oxidation states of which are dependent on the coexistent anions.

Syntheses, Characterization, and Antitumor Activities of Platinum(II) and Palladium(II) Complexes with Sugar-Conjugated Triazole Ligands

Four platinum(II) and palladium(II) complexes with sugar‐conjugated bipyridine‐type triazole ligands, [PtIICl2(AcGlc‐pyta)] (3), [PdIICl2(AcGlc‐pyta)] (4), [PtIICl2(Glc‐pyta)] (5), and [PdIICl2(Glc‐pyta)] (6), were prepared and characterized by mass spectrometry, elemental analysis, 1H‐ and 13C‐NMR, IR as well as UV/VIS spectroscopy, where AcGlc‐pyta and Glc‐pyta denote 2‐[4‐(pyridin‐2‐yl)‐1H‐1,2,3‐triazol‐1‐yl]ethyl 2,3,4,6‐tetra‐O‐acetyl‐β‐D‐glucopyranoside (1) and 2‐[4‐(pyridin‐2‐yl)‐1H‐1,2,3‐triazol‐1‐yl]ethyl β‐D‐glucopyranoside (2), respectively. The solid‐state structure of complex 6 was determined by single‐crystal X‐ray‐diffraction analysis. These complexes exhibited in vitro cytotoxicity against human cervix tumor cells (HeLa) though weaker than that of cisplatin.

Thia-calix[n]pyridines, synthesis and coordination to Cu(i,ii) ions with both N and S donor atomsElectronic supplementary information (ESI) available: emission spectra of compound 1. See http://www.rsc.org/suppdata/cc/b2/b203540e/

The novel thia-calix[n]pyridines (n = 3, 4, 6) coordinated to copper ions through nitrogen and sulfur atoms to give multinuclear complexes whose structures have been determined by X-ray crystallography and NMR spectra.

Direct Observation by Electrospray Ionization Mass Spectrometry of [Cp*RhMo3O8(OMe)5]−, a Key Intermediate in the Formation of the Double‐Bookshelf‐Type Oxide Cluster [(Cp*Rh)2Mo6O20(OMe)2]2−

The use of methanol as solvent is essential for the formation of the double-bookshelf-type oxide cluster [(Cp*Rh)(2)Mo(6)O(20)(OMe)(2)](2-) from [{Cp*Rh(µ-Cl)Cl}(2)] and four equivalents of [Mo(2)O(7)](2-). The reaction proceeds via [Cp*RhMo(3)O(8)(OMe)(5)](-). The proposed structure for this key intermediate (shown schematically) is supported by electrospray ionization mass spectrometry and labeling experiments with CD(3)OD as solvent. Cp*=eta(5)-C(5)Me(5).

The mono- and dinuclear copper(II) complexes containing tripodal ligand and pyridine, imidazole or pyrazole

Abstract Monomeric and dimeric copper(II) complexes containing tris(2-benzimidazylmethyl)amine (L 1 ) or its derivatives (L 2 , L 3 , L 4 and L 5 ) and pyridine (Py), imidazole (ImH) or pyrazole (Pz) have been prepared and characterized by their magnetic susceptibilities, electric conductivities, cyclic voltammetric half-wave potentials, and visible absorption and ESR spectra. The compounds made of L 2 , L 3 or L 4 and imidazole are dinuclear copper(II) complexes bridged by imidazolate, while other complexes are mononuclear ones. The susceptibility of [Cu 2 (L 2 ) 2 (Im)](ClO 4 ) 3 ·3H 2 O shows an antiferromagnetic interaction ( J = −30 cm −1 ) and the X-band ESR spectrum for the powdered sample of this complex exhibits the triplet state of such a dimer in the Δ M s = 2 region. Likewise, the signals due to the Δ M s = 2 transition were also observed for the complexes [Cu 2 (L 3 ) 2 (Im)](ClO 4 ) 3 ·2H 2 O and [Cu 2 (L 4 ) 2 (Im)](ClO 4 ) 3 ·2H 2 O. From the comparison of half-wave potentials ( E 1 2 ) in a series of monomeric copper(II) complexes, the E 1 2 values for the reduction of Cu(II) to Cu(I) decrease in the order Py > Pz > ImH in DMF and CH 3 CN solutions.

Laser photolysis studies on CuI complexes of thia-calix[3]pyridine. Phosphorescence from the intramolecular charge-transfer excited state

Abstract Copper(I) complexes of thia-calix[3]pyridine in dichloromethane exhibit phosphorescence from the MLCT triplet states at room temperature. The phosphorescence spectrum shifts to red on going from 300 to 180 K. The laser photolysis study carried out in the temperature range 300–180 K reveals that phosphorescence originates from the two triplet states, T H and T L , which are in thermal equilibrium with the energy difference of ca. 5 kcal mol −1 .