Ok-Sang Jung

Synthesis and antitumor activity of novel polyphosphazene-(diamine)platinum(II) conjugates

Abstract A novel class of water-soluble polyphosphazene-(diamine)platinum(II) conjugate drugs [N=P(S)Am·PtA 2 )] n have been designed and synthesized by incorporating the antitumor (diamine)platinum(II) moiety (A 2 Pt 2+ ) to a polyphosphazene back-bone along with a solubilizing groups (S) employing dicarboxylic amino acid (Am) as a spacer group. After characterization of these polymer conjugates by means of multinuclear ( 1 H, 31 P, 195 Pt) NMR and IR spectroscopies, elemental analysis and GPC, their antitumor activity were evaluated both in vitro and in vivo against murine leukemia L1210 cell lines and in vitro against five human tumor cell lines. Most of the title polymer conjugates have shown higher in vivo antitumor activity than cisplatin, and in particular [N=P(OH)(Glu·Pt(DACH))] n (Glu=glutamate, DACH= trans (±)-1,2-diaminocyclohexane) exhibit extraordinary high activity (ILS(%)>500) without cross-resistance to cisplatin as well as good water solubility, and therefore, was subjected to preclinical studies for human clinical trials.

Tris(pyrazolyl)borate complexes of 3-methoxy-3-oxopropyltin(IV). Crystal structure and properties of CH3OOCCH2CH2Sn((pz)3BH)X2 (X = Cl, NCS)

Abstract (Hydrotris(pyrazolyl)borato)(3-methoxy-3-oxopropyl)tin(IV) compounds, CH 3 OOCCH 2 CH 2 Sn((pz) 3 BH)X 2 ( 1 : X = Cl; 2 : X = NCS), have been prepared and examined. The X-ray crystal structures of 1 ·CH 2 Cl 2 ( C 2/ c ; a 20.658(4), b 8.848(1), c 26.485(5) A, β 109.73(1)°; Z = 8; R = 0.540) and 2 ·C 6 H 6 ( P 1 ; a 9.756(1), b 11.783(1), c 13.407(1) A, α 110.236(9), β 106.647(8), γ 95.842(8)°; Z = 2; R = 0.0463) shows discrete molecules containing a distorted octahedral tin atom, and a facial tridentate hydrotris(pyrazolyl)borate ligand; the carbonyl oxygen atom of 3-methoxy-3-oxopropyl group is released from the tin atom to accommodate the negative tridentate ligand. The spectral and the cryoscopic data for solid state or in solution are consistent with the crystal structures.

Synthesis and properties of diamine(isopropylidenemalonato) platinum(II): Crystal structure of O(CH2CH2)2C(CH2NH2)2Pt(OOC)2CC(CH3)2

Abstract New platinum(II) complexes of A 2 Pt(IPM) [A 2 = tetrahydro-4H-pyran-4,4-di(methylamine) (THPDMA), 2,2-dimethyl-1,3-propanediamine (DMPDA), trans -(±)-diaminocyclohexane (DACH); A = NH 3 , isopropylamine (IPA), cyclopropylamine (CPA); IPM = isopropylidenemalonate] have been synthesized and characterized by means of X-ray crystallography and various spectroscopies. The crystal structure of (THPDMA)Pt (IPM) · 5H 2 O was determined. The platinum atom adopts a typical square planar arrangement with two nitrogen atoms in the cis positions. The molecular structures are retained in aqueous solution at room temperature. However, the present complexes change to dimethyl sulphoxide (DMSO) adducts on standing for a long time or increasing temperature in DMSO : the monodentate amine complex produces (A)(DMSO)Pt(OOC) 2 CC(CH 3 ) 2 , whereas the chelate amine analogue affords A 2 Pt + (DMSO)(OOC)C(COO − )C(CH 3 ) 2 .

Oxidation of Pt(II) to Pt(IV) complex with hydrogen peroxide in glycols

Abstract The reaction of cis, cis-[PtII(9-fm)(dmpda)] (9-fm=9-fluorenylidenemalonate, dmpda=2,2-dimethyl-1,3-propanediamine) with hydrogen peroxide in ethyleneglycol produces cis,trans,cis-[PtIV(9-fm)(OCH2CH2OH)(OH)(dmpda)]. Its crystal structure shows that the local geometry around the platinum atom approximates a typical octahedral arrangement with the added OCH2CH2OH/OH ligands in trans coordination sites. The molecules are packed in a two-dimensional assembly via van der Waals interactions, where the hydrophobic fluorenyl groups are arranged on both faces of the assembly plate whereas the hydrophilic groups fill up the inner part of the plate. The compound bearing both “inorganic OH” and “organic OH” is a potential precursor for further various functionalizations.

Preparation and structure of CH3OOCCH2CH(COOCH3)CH2SnCl3

Abstract The novel estertin, CH 3 OOCCH 2 CH(COOCH 3 )CH 2 SnCl 3 , has been prepared and examined. The crystal ( Pna 2 1 ; a 13.626(3), b 7.323(2), c 12.727(3) A; Z = 4; R = 0.046) adopts a distorted octahedral arrangement with the five- and six-membered fused rings via two carbonyl oxygen-to-tin coordinations. However, IR and multinuclear NMR spectroscopy in solution suggests that one carbonyl group of the tin compound is released from the tin atom, which results in a five coordinate in atom in solution.

An organometallic mercaptopyridine complex with unusual bond shift fluxionality: metal-mediated tautomerism of (pentamethylcyclopentadienyl)bis(pyridine-2-thiolato)rhodium(III)

Abstract Studies have been carried out on unique molecular non-rigidity of Cp*RhIII(PyS)2 (PyS=pyridine-2-thiolato). One PyS ligand bonds to the rhodium ion in an S-monodentate mode (RhS(2)=2.3799(9) A) while the other ligand chelates to the metal in an N,S-bidentate mode (RhS(1)=2.4380(9); RhN(1)=2.089(2) A). Both PyS ligands possess a significant contribution from the thiol tautomer in the solid state. Even though the conformation and configuration of the molecule are still retained in solution, an unusual metal-mediated tautomeric non-rigidity for the PyS region is observed in the solution around room temperature.

A unique castle-wall type strand. Deca-coordinate cerium(III) complex with 3,3′-dihydroxy-2,2′-bipyridine

Abstract The reaction of cerium(III) nitrate with 3,3′-dihydroxy-2,2′-bipyridine (L) produces a coordination polymer of [Ce(NO 3 ) 3 (L)(H 2 O) 2 ] unit. L connects two Ce(III) ions via the oxygen donors of hydroxyl groups to give a castle-wall type strand. The Ce(III) ion is surrounded by deca oxygen donors including the bridged hydroxyl groups. Among the Ce(III)–O bonds, the bond length is the order of L>H 2 O>NO 3 − .

Synthesis and structural properties of (diamine) platinum(II) complexes of bis(alkylthio) methylenepropanedioic acid. Insight into bonding mode

Abstract New (diamine)platinum(II) complexes of bis(alkylthio)methylenepropanedioate ligandss, A 2 Pt(RS) 2 CC(COO − ) 2 (ANH 3 or A 2  trans -(±)-1,2-diaminocyclohexane (DACH); RCH 3 or C 2 H 5 ), have been prepared and structurally characterized both in the solid state and in solution. The crystal structures of a bis(ethylthio)methylenepropanedioate (BETMP) complex, (DACH)Pt(BETMP) · 4H 2 O ( monoclinic , P2 1 , a = 11.022(2), b = 17.604(4), c = 11.426(5) A , β = 93.42(3)°, V = 2213(1) A 3 , Z = 4, R = 0.065 ). and a bis(methylthio)methylenepropanedioate (BMTMP) complex, (DACH)Pt(BMTMP) · 3H 2 O triclinic , P1, a = 9.082(3), b = 9.797(3), c = 11.493(4) A , α = 72.42(3), β = 74.28(3), γ = 84.93(3)°, V = 938.4(5) A 3 , Z = 2, R = 0.031) , exhibit that among the possible chelating modes (O,O′-, O,S− and S,S′-), the present anionic ligands coordinate to the platinum(II) atom only in S,S′-chelating fashion. The bond distances of P t -S are in the range 2.273(2)–2.276(5) A. For the title complexes, the diethyl groups of the BETMP ligand occupy anti positions to each other whereas the dimethyl groups fo the BMTMP ligand occupy syn positions in the solid state. However, NMR studies disclose that the BMTMP complexes exist as an isomeric mixture of syn and anti forms (1:2) in contrast to the retention of the anti isomeric form of the BETMP complexes in solution.

Synthesis and structural properties of diamineplatinum(II) and diamineplatinum(IV) complexes of alkylidenemalonic acids

Abstract New diamineplatinum(II) complexes of alkylidenemalonate ligands, A2Pt(OOC)2C=CR2 [A2 = ethylenediamine (en), propylenediamine (pn); R2 = 2CH3, (CH2)5] have been prepared. Subsequent oxidation of the complexes with H2O2 leads tothe corresponding dihydroxyplatinum(IV) complexes, cis, cis, trans-A2Pt((OOC)2C=CR2) (OH)2. Among the octahedral complexes, cis, cis, trans-(pn)Pt((OOC)2C=C(CH3)2(OH)2 and cis, cis, trans-A2Pt((OOC)2C= Download : Download full-size image H2)(OH)2 have been characterized by X-ray crystallographic analysis. The local geometry of the platinum(IV) atoms is approximately octahedral with hydroxide groups in trans positions. The boat conformation of the chelated dicar☐ylate ring in platinum(IV) complexes is less bent than that of the corresponding platinum(II) analogues. Car☐ylation of the hydroxide of A2Pt((OOC)2C=C(CH3)2)(OH)2 with acetic anhydride affords A2Pt((OOC)2C=C(CH2)4)CH2(OH)2 (OAc)2 (A2 =en, pn), whereas the reaction of A2Pt((OOC)2C= Download : Download full-size image H2(OH)2 under the same conditions does not produce the corresponding analogue. NMR spectra indicate that the structures of the title complexes are retained in aqueous solution.

Synthesis and structural properties of ylidenemalonatoplatinum(II) complexes

Abstract New platinum(II) complexes A 2 Pt(OOC) 2 CCR 2 ( 1 , A 2 = 3-aminohexahydroazepine, R 2 = −(CH 2 5 − ; 2 , A 2 = 3-aminohexahydroazepine, R = CH 3 ; 3 , A 2 = 3-aminohexahydroazepine, R 2 = −SCH 2 CH 2 S-; 4 , A = cyclopropylamine, R 2 = −SCH 2 CH 2 S-) have been prepared and characterized. The molecular structures of the representative complexes 1 · 2H 2 O and 4 · C 3 H 7 NO were determined by X-ray analysis. The platinum atoms for 1 · 2H 2 O and 4 · C 3 H 7 NO achieve a typical square planar arrangement with each nitron atom in cis position. For 1 · 2H 2 O an unusually short CC bond [1.298(18) A] has been observed in contrast to the corresponding bond [1.374(9)A] in 4 · C 3 H 7 NO. The spectroscopic and physicochemical data disclose that these platinum complexes are stable and their molecular structures are retained in aqueous solution.