Emerging Ruthenium-Glucose Complexes with Chemotherapeutic Potential and Inquiry into the Biochemical Mechanism of Action
Dr. Amanda L. Eckermann, Chemistry, Dr. Kristin Dittenhafer-Reed, Chemistry
Due to the severe toxicity of anticancer platinum complexes and acquired drug resistance, research has focused on arene ruthenium complexes as viable alternatives. Arene complexes of the formula [areneRu(µ2-L)Cl]2 and (areneRu)2(µ2-L)3+ (L = alkyl thiolate) are known to be cytotoxic with IC50 values in the micromolar and submicromolar ranges, respectively. Our goals are to investigate whether glucose ligands or hydrophobic ligands on cymene ruthenium complexes improve specificity for cancerous cells over normal cells. Reaction of the sodium salt of β-D-thioglucose with [cymeneCl2Ru]2 forms [(cymeneRu(µ2-thioglucose)Cl]2 (1) and (cymeneRu)2(µ2-thioglucose)3+ (2). These compounds were successfully purified by HPLC and characterized by NMR spectroscopy. Toxicity of 1 has been investigated in vitro. Half-sandwich arene ruthenium complexes with hydrophobic N-heterocyclic ligands of the formula (arene)Ru(L)Cl2 have been synthesized where L= 4-phenyl pyridine, isoquinoline, benzimidazole, and CF3, and have been investigated and characterized spectroscopically.
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