Heart disease is the major cause of death in diabetes, a disorder characterized by chronic hyperglycemia and cardiovascular complications. Although altered systemic regulation of transition metals in diabetes has been the subject of previous investigation, it is not known whether changed transition metal metabolism results in heart disease in common forms of diabetes and whether metal chelation can reverse the condition. We found that administration of the Cu-selective transition metal chelator trientine to rats with streptozotocin-induced diabetes caused increased urinary Cu excretion compared with matched controls. A Cu II -trientine complex was demonstrated in the urine of treated rats. In diabetic animals with established heart failure, we show here for the first time that 7 weeks of oral trientine therapy significantly alleviated heart failure without lowering blood glucose, substantially improved cardiomyocyte structure, and reversed elevations in left ventricular collagen and ␤ 1 integrin. Oral trientine treatment also caused elevated Cu excretion in humans with type 2 diabetes, in whom 6 months of treatment caused elevated left ventricular mass to decline significantly toward normal. These data implicate accumulation of elevated loosely bound Cu in the mechanism of cardiac damage in diabetes and support the use of selective Cu chelation in the treatment of this condition.

X-ray crystal structures of three salts of protonated triethylenetetramine, (H4TETA)4+, with succinate, maleate, and fumarate anions are reported. Structures of the complexes (H4-triethylenetetramine)(hydrogenmaleate)4·2H2O [(H4TETA)(Hmal)4·2H2O] (1), (H4-triethylenetetramine)(hydrogenfumarate)4·3.3H2O [(H4TETA)(Hfum)4·3.3H2O] (2), and (H4-triethylenetetramine)(succinate)2 [(H4TETA)(suc)2] (3) all form assemblies of alternating two-dimensional layers of (H4TETA)4+ and the anionic species via hydrogen-bond networks. Both classical and nonclassical hydrogen bonds between the protonated amine groups, anions, and water molecules were observed. X-ray powder diffraction measurements, differential thermal analysis/thermogravimetry, density vapor sorption, and Karl Fischer titration measurements were performed to obtain confirmatory information about the water content in the structures 1 and 2 and to examine polymorphism within the salts. The nonhydrated salt 3 was determined to be the most favorable salt formulation for use in medicinal applications.

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SF6-photosensitiZed IR laser pyrolysis of W(CO)6 in the gas phase at moderate temperatures leads to unsaturated W(CO)n (n < 6) species; these prove to be effective abstractors of O atoms from a range of organic substrates, and afford a simple, clean and low-energy route from carbonyl compounds into gas phase carbene chemistry.

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