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Metal ion coordination chemistry of medicinal interest

University of British Columbia

Basic coordination chemistry of metal ions of medicinal interest is investigated and reported. The syntheses of vanadium complexes are reported using the naturally occurring ligating moieties isomaltolate (ima⁻) and allomaltolate (ama⁻), as well as a newly synthesized, potentially tetradentate diaminodipyrone [en(ama)₂]²⁻. Complete characterization of the resulting compounds (trans-VO(ima)₂(H₂O), VO(ama)₂, V(ima)₃, V(ama)₃ and VO(en(ama)₂), including X-ray crystallography analyses for trans- VO(ima)₂(H₂O) and V(ima)₃, are presented herein. The crystal structure of trans- VO(ima)₂(H₂O) shows a coordinated water trans to vanadyl. Potentiometric titrations (25°C, 1= 0.16 M NaCl) were used to measure stability constants in the V(IV)- ima⁻, V(IV)- ama⁻ and V(V)- ama⁻ systems; these data were compared to previous data collected on the V-maltolate system. In vivo efficacy of these compounds to normalize the blood glucose levels of STZ diabetic rats was tested; all but VO(en(ama)₂) produced significant decreases in plasma glucose levels. The results were compared to those of the benchmark compound BMOV (VO(ma)₂, bis(maltolato)oxovanadium(IV)), a proven insulin-enhancing agent. Rhenium complexation to [en(ama)₂]²⁻ is also investigated. The resulting complex ReO(en(ama)₂)Cl was characterized by a variety of techniques including ID and 2D NMR spectroscopy. These results clearly point to asymmetric binding of the ligand to the metal centre, leaving O = Re - CI in a cis configuration. Novel complexes of Ga and In were synthesized with a group of hetero donor phosphinophenolate ligands (PO⁻, (orthohydroxophenyl)diphenylphosphine; MePO⁻, (2- hydroxo-5-methylphenyl)diphenylphosphine). The two metal ions interestingly show diversity in their chelation to phosphinophenolates. The RPO⁻ (R = H, Me) heterodonor ligand binds in a bidentate fashion through both the hard and the soft donor atoms to In; whereas, it only chelates Ga through the hard oxygen donor. Electrochemical synthesis proved to be a practical synthetic approach. In₂(PO)₃Cl₃, In(PO)₃ and In(MePO)₃ were synthesized by electrolysis. [In(MePO)(H₂O)Cl₂]₂ and Ga(HPO)Cl₃ were synthesized using MCI₃ (M = In and Ga respectively). Both dimetallic indium complexes, [In(MePO)(H₂O)Cl₂]₂ and In₂(PO)₃Cl₃, show the phenolate oxygens bridging between the two metal ions. All four In atoms are in a distorted octahedral geometry in both complexes with the former having a coordination sphere of PO₃CI₂ for both indium metal ions and the latter showing a coordination sphere of PO₃CI₂ for one indium and P₂O₃CI for the other. Ga(HPO)Cl₃ is a zwitterionic complex, with Ga having a OCI₃ coordination core. All these complexes were fully characterized including X-ray crystallography.

Text

2009-12-23

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http://hdl.handle.net/2429/17200

Chemistry

University of British Columbia

UBCV

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