@article {1390, title = {Carbohydrate-appended 3-hydroxy-4-pyridinone complexes of the [M(CO)(3)](+) core (M) Re, Tc-99m, Re-186)}, journal = {Bioconjugate Chemistry}, volume = {17}, number = {5}, year = {2006}, note = {ISI Document Delivery No.: 085LXTimes Cited: 21Cited Reference Count: 69Ferreira, Cara L. Bayly, Simon R. Green, David E. Storr, Tim Barta, Cheri A. Steele, Jennifer Adam, Michael J. Orvig, Chris}, month = {Sep}, pages = {1321-1329}, type = {Article}, abstract = {This work describes the use of 3-hydroxy-4-pyridinone ligands for binding the [M(CO)(3)](+) core ( M) Re, Tc) in the context of preparing novel Tc( I) and Re( I) glucose conjugates. Five pyridinone ligands bearing pendent carbohydrate moieties, HL1-5, were coordinated to the [M(CO)(3)](+0) core on the macroscopic scale ( M) Re) and on the tracer scale (M) = Tc-99m, Re-186). On the macroscopic scale the complexes, ReL1-5(CO)(3)(H{\O}-2), were thoroughly characterized by mass spectrometry, IR spectroscopy, UV-visible spectroscopy, elemental analysis, and 1D/2D NMR spectroscopy. Characterization confirmed the bidentate coordination of the pyridinone and the pendent nature of the carbohydrate and suggests the presence of a water molecule in the sixth coordination site. In preliminary biological evaluation, both the ligands and complexes were assessed as potential substrates or inhibitors of hexokinase, but showed no activity. Labeling via the [Tc-99m(CO)(3)(H2O)(3)](+) precursor gave the tracer species (TcL1-5)-Tc-99m(CO)(3)(H2O) in high radiochemical yields. Similar high radiochemical yields when labeling with Re-186 were facilitated by in situ preparation of the [Re-186( CO)(3)(H2O)(3)](+) species in the presence of HL1-5 to give (ReL1-5)-Re-186(CO)(3)(H2O). Stability challenges, incubating (TcL1-5)-Tc-99m(CO)(3)(H2O) in the presence of excess cysteine and histidine, confirmed complex stability up to 24 h.}, keywords = {5-HT1A RECEPTOR, BIFUNCTIONAL LIGAND, BIOMOLECULES, GLUCOSE, IMAGING AGENTS, IN-VITRO, METAL-COMPLEXES, STRUCTURAL-CHARACTERIZATION, TRICARBONYL COMPLEXES, TRIDENTATE LIGANDS}, isbn = {1043-1802}, url = {://000240606700027}, author = {Ferreira, C. L. and Bayly, S. R. and Green, D. E. and Storr, T. and Barta, C. A. and Steele, J. and Adam,Michael J. and Orvig, Chris} } @article {1390, title = {Carbohydrate-appended 3-hydroxy-4-pyridinone complexes of the [M(CO)(3)](+) core (M) Re, Tc-99m, Re-186)}, journal = {Bioconjugate Chemistry}, volume = {17}, number = {5}, year = {2006}, note = {ISI Document Delivery No.: 085LXTimes Cited: 21Cited Reference Count: 69Ferreira, Cara L. Bayly, Simon R. Green, David E. Storr, Tim Barta, Cheri A. Steele, Jennifer Adam, Michael J. Orvig, Chris}, month = {Sep}, pages = {1321-1329}, type = {Article}, abstract = {This work describes the use of 3-hydroxy-4-pyridinone ligands for binding the [M(CO)(3)](+) core ( M) Re, Tc) in the context of preparing novel Tc( I) and Re( I) glucose conjugates. Five pyridinone ligands bearing pendent carbohydrate moieties, HL1-5, were coordinated to the [M(CO)(3)](+0) core on the macroscopic scale ( M) Re) and on the tracer scale (M) = Tc-99m, Re-186). On the macroscopic scale the complexes, ReL1-5(CO)(3)(H{\O}-2), were thoroughly characterized by mass spectrometry, IR spectroscopy, UV-visible spectroscopy, elemental analysis, and 1D/2D NMR spectroscopy. Characterization confirmed the bidentate coordination of the pyridinone and the pendent nature of the carbohydrate and suggests the presence of a water molecule in the sixth coordination site. In preliminary biological evaluation, both the ligands and complexes were assessed as potential substrates or inhibitors of hexokinase, but showed no activity. Labeling via the [Tc-99m(CO)(3)(H2O)(3)](+) precursor gave the tracer species (TcL1-5)-Tc-99m(CO)(3)(H2O) in high radiochemical yields. Similar high radiochemical yields when labeling with Re-186 were facilitated by in situ preparation of the [Re-186( CO)(3)(H2O)(3)](+) species in the presence of HL1-5 to give (ReL1-5)-Re-186(CO)(3)(H2O). Stability challenges, incubating (TcL1-5)-Tc-99m(CO)(3)(H2O) in the presence of excess cysteine and histidine, confirmed complex stability up to 24 h.}, keywords = {5-HT1A RECEPTOR, BIFUNCTIONAL LIGAND, BIOMOLECULES, GLUCOSE, IMAGING AGENTS, IN-VITRO, METAL-COMPLEXES, STRUCTURAL-CHARACTERIZATION, TRICARBONYL COMPLEXES, TRIDENTATE LIGANDS}, isbn = {1043-1802}, url = {://000240606700027}, author = {Ferreira, C. L. and Bayly, S. R. and Green, D. E. and Storr, T. and Barta, C. A. and Steele, J. and Adam,Michael J. and Orvig, Chris} } @article {1600, title = {Metal complexes in medicinal chemistry: new vistas and challenges in drug design}, journal = {Dalton Transactions}, number = {6}, year = {2006}, note = {ISI Document Delivery No.: 014YVTimes Cited: 60Cited Reference Count: 44}, month = {Feb}, pages = {761-764}, type = {Article}, abstract = {An overview is presented of selected metal-bases! pharmaceuticals, either diagnostic or therapeutic, with emphasis on specific attributes and in vivo interactions of these compounds relevant to their use in medicinal applications. Both the advantages and the challenges of this approach are outlined, with possibilities for future developments accentuated.}, keywords = {AGENTS, BINDING CONSTANTS, BIS(MALTOLATO)OXOVANADIUM(IV), GLUCOSE, HUMAN-SERUM TRANSFERRIN, MODULATION, therapy, TRANSPORT}, isbn = {1477-9226}, url = {://000235520000001}, author = {Thompson, K. H. and Orvig, Chris} } @article {1125, title = {Carbohydrate-bearing 3-hydroxy-4-pyridinonato complexes of gallium(III) and indium(III)}, journal = {Bioconjugate Chemistry}, volume = {16}, number = {6}, year = {2005}, note = {ISI Document Delivery No.: 985QSTimes Cited: 17Cited Reference Count: 38}, month = {Nov-Dec}, pages = {1597-1609}, type = {Article}, abstract = {Gallium and indium complexes with pendant carbohydrates have been prepared and examined for their potential as radiopharmaceuticals. Carbohydrate-bearing 3-hydroxy-4-pyridinone ligand precursors and their tris(ligand)gallium(III) and -indium(III) complexes were synthesized and characterized by mass spectrometry, elemental analysis, and H-1 and C-13 NMR spectroscopy, and in the case of one intermediate, by X-ray crystallography. With three equivalents of ligand, neutral complexes formed with the bidentate hydroxypyridinone moiety complexing the gallium(III) and indium(III) metal centers.}, keywords = {aluminum, ANALOGS, CITRATE, GLUCOSE, INVIVO, SYSTEM, TC-99M}, isbn = {1043-1802}, url = {://000233393800036}, author = {Green, D. E. and Ferreira, C. L. and Stick, R. V. and Patrick, B. O. and Adam,Michael J. and Orvig, Chris} } @article {1125, title = {Carbohydrate-bearing 3-hydroxy-4-pyridinonato complexes of gallium(III) and indium(III)}, journal = {Bioconjugate Chemistry}, volume = {16}, number = {6}, year = {2005}, note = {ISI Document Delivery No.: 985QSTimes Cited: 17Cited Reference Count: 38}, month = {Nov-Dec}, pages = {1597-1609}, type = {Article}, abstract = {Gallium and indium complexes with pendant carbohydrates have been prepared and examined for their potential as radiopharmaceuticals. Carbohydrate-bearing 3-hydroxy-4-pyridinone ligand precursors and their tris(ligand)gallium(III) and -indium(III) complexes were synthesized and characterized by mass spectrometry, elemental analysis, and H-1 and C-13 NMR spectroscopy, and in the case of one intermediate, by X-ray crystallography. With three equivalents of ligand, neutral complexes formed with the bidentate hydroxypyridinone moiety complexing the gallium(III) and indium(III) metal centers.}, keywords = {aluminum, ANALOGS, CITRATE, GLUCOSE, INVIVO, SYSTEM, TC-99M}, isbn = {1043-1802}, url = {://000233393800036}, author = {Green, D. E. and Ferreira, C. L. and Stick, R. V. and Patrick, B. O. and Adam,Michael J. and Orvig, Chris} } @article {1219, title = {Synthesis and insulin-mimetic activities of metal complexes with 3-hydroxypyridine-2-carboxylic acid}, journal = {Journal of Inorganic Biochemistry}, volume = {99}, number = {6}, year = {2005}, note = {ISI Document Delivery No.: 934IJTimes Cited: 16Cited Reference Count: 28}, month = {Jun}, pages = {1275-1282}, type = {Article}, abstract = {Metal complexes of 3-hydroxypyridine-2-carboxylic acid (H(2)hpic), [Co(Hhpic)(2)(H2O)(2)] (1), [Fe(Hhpic)(2)(H2O)(2)] (2), [Zn(Hhpic)(2)(H2O)(2)] (3), [Mn(Hhpic)(2)(H2O)(2)] (4), and [Cu(Hhpic)(2)] (5) have been synthesized and characterized by mass spectrometry, elemental analysis, magnetic susceptibility, infrared, electronic absorption and electron paramagnetic resonance (EPR) spectroscopies. The solid-state structure of 1 has been established by X-ray crystallography. The EPR spectra of 4 and 5 displayed six and four-line hyperfine splitting patterns, respectively, due to coupling of the unpaired electron with the Mn-55 (I=5/2) nucleus and the Cu-63 (I=3/2) nucleus. In the EPR spectrum of 5, an additional five-line super-hyperfine splitting pattern was observed at 77 K, caused by additional interaction of the unpaired electron with ligand nitrogen atoms (I=1), indicating that the structure of 5 was retained in dimethyl sulfoxide solution. The insulin-mimetic activity of these complexes was evaluated by means of in vitro measurements of the inhibition of free fatty acid (FFA) release from epinephrine-treated, isolated rat adipocytes. Complex 5 was found to exhibit the most potent insulin-mimetic activity among the complexes examined in this study. (C) 2005 Elsevier Inc. All rights reserved.}, keywords = {3-hydroxypyridine-2-carboxylic acid (H(2)hpic), CHEMISTRY, DIABETIC-RATS, GLUCOSE, insulin-mimetic drug, MECHANISM, MONONUCLEAR, RAT ADIPOCYTES, VANADIUM}, isbn = {0162-0134}, url = {://000229702200002}, author = {Nakai, M. and Sekiguchi, F. and Obata, M. and Ohtsuki, C. and Adachi, Y. and Sakurai, H. and Orvig, Chris and Rehder, D. and Yano, S.} } @article {805, title = {Carbohydrate conjugates for molecular imaging and radiotherapy: Tc-99m(I) and Re-186(I) tricarbonyl complexes of N-(2 {\textquoteright}-hydroxybenzyl)-2-amino-2-deoxy-D-glucose}, journal = {Bioconjugate Chemistry}, volume = {15}, number = {4}, year = {2004}, note = {ISI Document Delivery No.: 840SWTimes Cited: 39Cited Reference Count: 17}, month = {Jul-Aug}, pages = {923-926}, type = {Article}, abstract = {An approach to a new class of potential radiopharmaceuticals is demonstrated by the labeling of a glucosamine derivative with the tricarbonyls of Tc-99m and Re-186. The proligand HL2 (N-(2{\textquoteright}-hydroxybenzyl)-2-amino-2-deoxy-d-glucose) was produced by hydrogenation of the corresponding Schiff base and reacted with [NEt4](2)[Re(CO)(3)Br-3] to form the neutral complex [(L-2)Re(CO)(3)] in 40\% yield. H-1 and C-13 NMR spectra indicate that the {Re(CO)(3)} core is bound in a tridentate fashion via the amino N, phenolato O, and C-3 hydroxyl O atoms of the ligand. At the tracer-level, labeling of HL2 with [Tc-99m(CO)(3)(H2O)(3)](+) and [Re-186(CO)(3)(H2O)(3)](+) was achieved in aqueous conditions in 95 +/- 2\% and 94 +/- 3\% average radiochemical yields, respectively.}, keywords = {BIOMOLECULES, GLUCOSE, LIGAND SYSTEMS, RADIOPHARMACEUTICALS, SUGARS}, isbn = {1043-1802}, url = {://000222880900032}, author = {Bayly, S. R. and Fisher, C. L. and Storr, T. and Adam,Michael J. and Orvig, Chris} } @article {805, title = {Carbohydrate conjugates for molecular imaging and radiotherapy: Tc-99m(I) and Re-186(I) tricarbonyl complexes of N-(2 {\textquoteright}-hydroxybenzyl)-2-amino-2-deoxy-D-glucose}, journal = {Bioconjugate Chemistry}, volume = {15}, number = {4}, year = {2004}, note = {ISI Document Delivery No.: 840SWTimes Cited: 39Cited Reference Count: 17}, month = {Jul-Aug}, pages = {923-926}, type = {Article}, abstract = {An approach to a new class of potential radiopharmaceuticals is demonstrated by the labeling of a glucosamine derivative with the tricarbonyls of Tc-99m and Re-186. The proligand HL2 (N-(2{\textquoteright}-hydroxybenzyl)-2-amino-2-deoxy-d-glucose) was produced by hydrogenation of the corresponding Schiff base and reacted with [NEt4](2)[Re(CO)(3)Br-3] to form the neutral complex [(L-2)Re(CO)(3)] in 40\% yield. H-1 and C-13 NMR spectra indicate that the {Re(CO)(3)} core is bound in a tridentate fashion via the amino N, phenolato O, and C-3 hydroxyl O atoms of the ligand. At the tracer-level, labeling of HL2 with [Tc-99m(CO)(3)(H2O)(3)](+) and [Re-186(CO)(3)(H2O)(3)](+) was achieved in aqueous conditions in 95 +/- 2\% and 94 +/- 3\% average radiochemical yields, respectively.}, keywords = {BIOMOLECULES, GLUCOSE, LIGAND SYSTEMS, RADIOPHARMACEUTICALS, SUGARS}, isbn = {1043-1802}, url = {://000222880900032}, author = {Bayly, S. R. and Fisher, C. L. and Storr, T. and Adam,Michael J. and Orvig, Chris} } @article {966, title = {The mechanism of the reaction catalyzed by ADP-beta-L-glycero-D-manno-heptose 6-epimerase}, journal = {Journal of the American Chemical Society}, volume = {126}, number = {29}, year = {2004}, note = {ISI Document Delivery No.: 840JTTimes Cited: 14Cited Reference Count: 24}, month = {Jul}, pages = {8878-8879}, type = {Article}, keywords = {4, 6-DEHYDRATASE, BACTERIA, D-MANNOHEPTOSE 6-EPIMERASE, EPIMERIZATION, ESCHERICHIA-COLI, GLUCOSE, INSIGHTS, NUCLEOTIDE-MODIFYING ENZYMES, OUTER-MEMBRANE, UDP-GALACTOSE 4-EPIMERASE}, isbn = {0002-7863}, url = {://000222855300009}, author = {Read, J. A. and Ahmed, R. A. and Morrison, J. P. and Coleman, W. G. and Tanner, M. E.} } @article {509, title = {Synthesis and solution studies of the complexes of pyrone analogue ligands with vanadium(IV) and vanadium(V)}, journal = {Inorganica Chimica Acta}, volume = {339}, year = {2002}, note = {ISI Document Delivery No.: 616BDTimes Cited: 8Cited Reference Count: 16}, month = {Nov}, pages = {393-399}, type = {Article}, abstract = {A new potentially tetradentate chelator N,N{\textquoteright}-bis(3-hydroxy-6-methyl-2-methylene-4-pyrone)ethylenediamine (H-2(en(ama)(2))), has been synthesized and its protonation constants, as well as those of two other 3-hydroxy-4-pyrone ligands (allomaltol (Hama) and methylmaltol (Hmma)) determined potentiometrically at 25 degreesC and 0.16 M NaCl: pK(a1) = 3.67+/-0.07, pK(a2) = 5.82+/-0.07, pK(a3) = 7.96+/-0.04, pK(a4) = 8.77+/-0.03 for [H-4(en(ama)(2))](2+), pK(a) = 8.04+/-0.02 for Hama and pK(a) = 8.82+/-0.02 for Hmma. Potentiometric pH titrations were also used to measure the stability constants of these ligands with V(IV) and V(V) and to study the structures of the complexes of (en(ama)(2))(2-) in aqueous solution. H-1 NMR was used to assign the protonation constant values to the different protons in H-2(en(ama)(2)). A pM versus pH plot confirmed that H-2(en(ama)(2)) has much stronger complexation than its bidentate analogues, in the same pH range. (C) 2002 Elsevier Science B.V. All rights reserved.}, keywords = {AQUEOUS-SOLUTION, BIS(MALTOLATO)OXOVANADIUM(IV), GLUCOSE, insulin drugs, ION-COORDINATING PROPERTIES, potentiometry, stability constants, vanadium complexes}, isbn = {0020-1693}, url = {://000179281100048}, author = {Song, B. and Saatchi, K. and Rawji, G. H. and Orvig, Chris} } @article {5148, title = {Insulin-enhancing vanadium(III) complexes}, journal = {Inorganic Chemistry}, volume = {40}, number = {18}, year = {2001}, note = {ISI Document Delivery No.: 466JNTimes Cited: 67Cited Reference Count: 54}, month = {Aug}, pages = {4686-4690}, type = {Article}, abstract = {Simple, high-yield, large-scale syntheses of the V(III) complexes tris(maltolato)vanadium(III), V(ma)(3), tris-(ethyhmaltolato)vanadium(HI), V(ema)(3), tris(kojato)vanadium(III) monchydrate, V(koj)(3).H2O, and tris(1,2-dimethyl-3-hydroxy-4-pyridinonato)vanadium(III) dodecahydrate, V(dpp)(3). 12H(2)O, are described; the characterization of these complexes by various methods and, in the case of V(dpp)(3). 12H(2)O, by an X-ray crystal structure determination, is reported. The ability of these complexes to normalize glucose levels in the STZ-diabetic rat model has been examined and compared with that of the benchmark compound BMOV (bis(maltolato)oxovanadium(IV)), an established insulin-enhancing agent.}, keywords = {AGENT, aluminum, BIS(MALTOLATO)OXOVANADIUM(IV), CHELATE COMPLEXES, COORDINATION CHEMISTRY, CRYSTAL-STRUCTURE, DIABETIC RATS, gallium, GLUCOSE, LIGANDS, MIMETIC}, isbn = {0020-1669}, url = {://000170642600028}, author = {Melchior, M. and Rettig, S. J. and Liboiron, B. D. and Thompson, K. H. and Yuen, V. G. and McNeill, J. H. and Orvig, Chris} } @article {4616, title = {Vanadium complexes as insulin mimetic agents: Coordination chemistry and in vivo studies of oxovanadium(IV) and dioxovanadate(V) complexes formed from naturally occurring chelating oxazolinate, thiazolinate, or picolinate units}, journal = {Inorganic Chemistry}, volume = {38}, number = {10}, year = {1999}, note = {ISI Document Delivery No.: 199BHTimes Cited: 72Cited Reference Count: 34}, month = {May}, pages = {2288-2293}, type = {Article}, abstract = {{The synthesis and characterization of four complexes containing naturally occurring binding groups are reported: VO(pic)(2). H2O (Hpic = picolinic or pyridine-2-carboxylic acid), NH4[VO2(pic)(2)]. 2H(2)O, VO(oz)(2) (Hoz = 2-(2{\textquoteright}- hydroxyphenyl)-2-oxazoline), and VO(thoz)(2) (Hthoz = 2-(2{\textquoteright}-hydroxyphenyl)-2-thiazoline). The X-ray structures of [NH4[VO2(pic)(2)]. 2H(2)O, VO(oz)(2), and VO(thoz)(2) have been determined. Crystals of NH4[VO2(pic)(2)]. 2H(2)O (C12H12N3O6V . 2H(2)O) are monoclinic, space group Cc, a 10.347(2) Angstrom}, keywords = {BIS(MALTOLATO)OXOVANADIUM(IV), BMOV, CRYSTAL-STRUCTURE, DIABETIC RATS, GLUCOSE, NMR, SIDEROPHORE, SULFATE, SYSTEM, VANADATE}, isbn = {0020-1669}, url = {://000080459200009}, author = {Melchior, M. and Thompson, K. H. and Jong, J. M. and Rettig, S. J. and Shuter, E. and Yuen, V. G. and Zhou, Y. and McNeill, J. H. and Orvig, Chris} } @article {4399, title = {Kinetic analysis and comparison of uptake, distribution, and excretion of V-48-labeled compounds in rats}, journal = {Journal of Applied Physiology}, volume = {84}, number = {2}, year = {1998}, note = {ISI Document Delivery No.: YU964Times Cited: 63Cited Reference Count: 43}, month = {Feb}, pages = {569-575}, type = {Article}, abstract = {Vanadium has been found to be orally active in lowering plasma glucose levels; thus it provides a potential treatment for diabetes mellitus. Bis(maltolato)oxovanadium(rv) (BMOV) is a well-characterized organovanadium compound that has been shown in preliminary studies to have a potentially useful absorption profile. Tissue distributions of BMOV compared with those of vanadyl sulfate (VS) were studied in Wistar rats by using V-48 as a tracer. In this study, the compounds were administered in carrier-added forms by either oral gavage or intraperitoneal injection. Data analyzed by a compartmental model, by using simulation, analysis, and modeling (i.e., SAAM II) software, showed a pattern of increased tissue uptake with use of V-48-BMOV compared with (VS)-V-48. The highest V-48 concentrations at 24 h after gavage were in bone, followed by kidney and liver. Most ingested V-48 was eliminated unabsorbed by fecal excretion. On average, V-48 concentrations in bone, kidney, and liver 24 h after oral administration of V-48-BMOV were two to three times higher than those of (VS)-V-48, which is consistent with the increased glucose-lowering potency of BMOV in acute glucose lowering compared with VS.}, keywords = {ADIPOCYTES, analysis, and modeling, BIS(MALTOLATO)OXOVANADIUM(IV), compartmental modeling, diabetes, DISSOCIATION, FERRIC MALTOL, GLUCOSE, INDUCED DIABETIC RATS, INSULIN, insulin mimetic, METABOLISM, MOLYBDENUM, SIMULATION, SMALL-INTESTINE, Software, VANADIUM, VANADYL SULFATE}, isbn = {8750-7587}, url = {://000071774300025}, author = {Setyawati, I. A. and Thompson, K. H. and Yuen, V. G. and Sun, Y. and Battell, M. and Lyster, D. M. and Vo, C. and Ruth, T. J. and Zeisler, S. and McNeill, J. H. and Orvig, Chris} } @article {3690, title = {Characterization of the potent insulin mimetic agent bis(maltolato)oxovanadium(IV) (BMOV) in solution by EPR spectroscopy}, journal = {Inorganic Chemistry}, volume = {35}, number = {22}, year = {1996}, note = {ISI Document Delivery No.: VP449Times Cited: 63Cited Reference Count: 48}, month = {Oct}, pages = {6507-6512}, type = {Article}, abstract = {{Bis(maltolato)oxovanadium(IV) (abbreviated BMOV or VO(ma)(2)) has been characterized by electron paramagnetic resonance (EPR) spectroscopy in CH2Cl2, H2O, MeOH, and pyridine at both room and low temperatures. Spin Hamiltonian parameters for mono- and bis(maltolato)oxovanadium(IV) complexes [VO(ma)](+) (=[VO(ma)(H2O)(n)](+)}, keywords = {ADIPOCYTES, CHEMISTRY, DIABETIC RATS, ELECTRON-PARAMAGNETIC-RES, FUTURE, GLUCOSE, KINASE, MIMICS, SULFATE, treatment, VANADYL COMPLEXES}, isbn = {0020-1669}, url = {://A1996VP44900022}, author = {Hanson, G. R. and Sun, Y. and Orvig, Chris} } @article {3447, title = {Increased potency of vanadium using organic ligands}, journal = {Molecular and Cellular Biochemistry}, volume = {153}, number = {1-2}, year = {1995}, note = {ISI Document Delivery No.: TM620Times Cited: 45Cited Reference Count: 46Vanadium SymposiumJUL 29-31, 1994MONTREAL, CANADACanadian Diabet Assoc, Fonds Rech Sante Quebec, Juvenile Diabet Fdn Canada, Marion Merrell Dow Canada, McGill Univ, Med Res Council Canada, Medisense Canada Inc, Merck Frosst, Canada Inc, Miles Canada Inc}, month = {Dec}, pages = {175-180}, type = {Proceedings Paper}, abstract = {The in vivo glucose lowering effect of orally administered inorganic vanadium compounds in diabetes was first reported in our laboratory in 1985. While both vanadate and vanadyl forms of vanadium are orally active, they are still not well absorbed. We have synthesized several organic vanadium compounds and one compound, bis(maltolato)oxovanadium(lv) or BMOV, has been extensively investigated. BMOV proved effective in lowering plasma glucose and lipids in STZ-diabetic: rats when administered in drinking water over a 25 week period. The maintenance dose (0.18 mmol/kg/day) was approximately 50\% of that required for vanadyl sulfate (VS). Secondary complications of diabetes were prevented by BMOV and no marked toxicity was noted. Oral gavage of STZ-diabetic rats with BMOV also reduced blood glucose levels. The ED(50) for BMOV was 0.5 mmol/kg, while for VS the estimated ED(50) was 0.9 mmol/kg. BMOV was also effective by the intraperitoneal route in STZ-diabetic rats. The ED(50) was 0.08 mmol/kg compared to 0.22 mmol/kg for VS. Some animals treated p.o. or i.p. remained euglycemic for up to 14 weeks. An i.v. infusion of BMOV of 0.05 mmol/kg over a 30 min period reduced plasma glucose levels by 50\% while VS was not effective.}, keywords = {ADIPOCYTES, BIS(MALTOLATO)OXOVANADIUM(IV), diabetes, DIABETIC, GLUCOSE, HYPERTENSION, IMPROVEMENT, INSULIN ACTION, insulin-mimetic, RATS, RECEPTOR TYROSINE KINASE, resistance, SPONTANEOUSLY HYPERTENSIVE RATS, VANADATE, VANADIUM}, isbn = {0300-8177}, url = {://A1995TM62000024}, author = {McNeill, J. H. and Yuen, V. G. and Dai, S. T. and Orvig, Chris} } @article {3265, title = {Reaction chemistry of BMOV, bis(maltolato)oxovanadium(IV) - A potent insulin mimetic agent}, journal = {Journal of the American Chemical Society}, volume = {117}, number = {51}, year = {1995}, note = {ISI Document Delivery No.: TM483Times Cited: 165Cited Reference Count: 66}, month = {Dec}, pages = {12759-12770}, type = {Article}, abstract = {{The reaction chemistry of the potent insulin-mimetic agent bis(maltolato)oxovanadium(IV) (abbreviated BMOV or VO(ma)(2)) is reported. VO(ma)(2) (log K-1 = 8.80(2), log K-2 = 7.51(2), log beta(2) = 16.31(3)) has a rich coordination chemistry, forming a number of V(IV) and V(V) derivatives. In aqueous solution it is slowly oxidized by molecular oxygen to [VO2(ma)(2)](-) (log K-1 = 7.5(1), log K-2 = 6.2(1), log beta(2) = 13.7(1)); in alcohols a variety of V(V) analogs VO(OR)(ma)(2) (R = CH3, C2H5, i-C3H7) are formed by aerial oxidation. All these vanadate complexes can be interconverted by reaction with the appropriate alcohol or water. In addition, the six-coordinate V(IV) pyridine adduct VO(ma)(2)py can be formed and this undergoes oxidation to V(V) complexes much more slowly, demonstrating that a vacant coordinate site is required for the coordination of O-2 to VO(ma)(2) before inner-sphere oxidation can take place. V-51 NMR and electrochemistry have been studied as a function of pH; a complete study of the aqueous chemistry of VO(ma)(2) and [VO2(ma)(2)](-) has been undertaken because the oral activity of VO(ma)(2) as an insulin-mimetic may be related to the chemical properties of the two compounds in water. Oral gavage studies in STZ-diabetic rats have been performed which showed that the intact complex is required for activity and that the presence of a biologically compatible reducing agent, ascorbic acid, neither interferes with nor augments the insulin-mimetic effect of VO(ma)(2). The X-ray structures of VO(ma)(2) and the cis-VO2 compound K[VO2(ma)(2)]. H2O have been determined; crystals of VO(ma)(2)[BMOV] are monoclinic, P2(1)/n}, keywords = {aluminum, DIABETIC RATS, DISSOCIATION, GLUCOSE, ISOLATED RAT ADIPOCYTES, MALTOL COMPLEX, METABOLISM, METAL CHELATE COMPLEXES, RECEPTOR KINASE, VANADYL COMPLEXES}, isbn = {0002-7863}, url = {://A1995TM48300013}, author = {Caravan, P. and Gelmini, L. and Glover, N. and Herring, F. G. and Li, H. L. and McNeill, J. H. and Rettig, S. J. and Setyawati, I. A. and Shuter, E. and Sun, Y. and Tracey, A. S. and Yuen, V. G. and Orvig, Chris} } @article {3265, title = {Reaction chemistry of BMOV, bis(maltolato)oxovanadium(IV) - A potent insulin mimetic agent}, journal = {Journal of the American Chemical Society}, volume = {117}, number = {51}, year = {1995}, note = {ISI Document Delivery No.: TM483Times Cited: 165Cited Reference Count: 66}, month = {Dec}, pages = {12759-12770}, type = {Article}, abstract = {{The reaction chemistry of the potent insulin-mimetic agent bis(maltolato)oxovanadium(IV) (abbreviated BMOV or VO(ma)(2)) is reported. VO(ma)(2) (log K-1 = 8.80(2), log K-2 = 7.51(2), log beta(2) = 16.31(3)) has a rich coordination chemistry, forming a number of V(IV) and V(V) derivatives. In aqueous solution it is slowly oxidized by molecular oxygen to [VO2(ma)(2)](-) (log K-1 = 7.5(1), log K-2 = 6.2(1), log beta(2) = 13.7(1)); in alcohols a variety of V(V) analogs VO(OR)(ma)(2) (R = CH3, C2H5, i-C3H7) are formed by aerial oxidation. All these vanadate complexes can be interconverted by reaction with the appropriate alcohol or water. In addition, the six-coordinate V(IV) pyridine adduct VO(ma)(2)py can be formed and this undergoes oxidation to V(V) complexes much more slowly, demonstrating that a vacant coordinate site is required for the coordination of O-2 to VO(ma)(2) before inner-sphere oxidation can take place. V-51 NMR and electrochemistry have been studied as a function of pH; a complete study of the aqueous chemistry of VO(ma)(2) and [VO2(ma)(2)](-) has been undertaken because the oral activity of VO(ma)(2) as an insulin-mimetic may be related to the chemical properties of the two compounds in water. Oral gavage studies in STZ-diabetic rats have been performed which showed that the intact complex is required for activity and that the presence of a biologically compatible reducing agent, ascorbic acid, neither interferes with nor augments the insulin-mimetic effect of VO(ma)(2). The X-ray structures of VO(ma)(2) and the cis-VO2 compound K[VO2(ma)(2)]. H2O have been determined; crystals of VO(ma)(2)[BMOV] are monoclinic, P2(1)/n}, keywords = {aluminum, DIABETIC RATS, DISSOCIATION, GLUCOSE, ISOLATED RAT ADIPOCYTES, MALTOL COMPLEX, METABOLISM, METAL CHELATE COMPLEXES, RECEPTOR KINASE, VANADYL COMPLEXES}, isbn = {0002-7863}, url = {://A1995TM48300013}, author = {Caravan, P. and Gelmini, L. and Glover, N. and Herring, F. G. and Li, H. L. and McNeill, J. H. and Rettig, S. J. and Setyawati, I. A. and Shuter, E. and Sun, Y. and Tracey, A. S. and Yuen, V. G. and Orvig, Chris} }