Synthesis and characterization of V^IVO complexes of picolinate and pyrazine derivatives: behavior in the solid state and aqueous solution and biotransformation in the presence of blood plasma proteins

Oxidovanadium(IV) complexes with 5-cyanopyridine-2-carboxylic acid (HpicCN), 3,5-difluoropyridine-2-carboxylic acid (HpicFF), 3-hydroxypyridine-2-carboxylic acid (H2hypic), and pyrazine-2-carboxylic acid (Hprz) have been synthesized and characterized in the solid state and aqueous solution through elemental analysis, IR and EPR spectroscopy, potentiometric titrations, and DFT simulations. The crystal structures of the complexes (OC-6-23)-[VO(picCN)2(H2O)]•2H2O (1•2H2O), (OC-6-24)-[VO(picCN)2(H2O)]•4H2O (2•4H2O), (OC-6-24)-Na[VO(Hhypic)3]•H2O (4), and two enantiomers of (OC-6-24)-[VO(prz)2(H2O)] (Λ-5 and Δ-5) have been determined also by X-ray crystallography. 1 presents the first crystallographic evidence for the formation of a OC-6-23 isomer for bis(picolinato) VIVO complexes, whereas 2, 4, and 5 possess the more common OC-6-24 arrangement. The strength order of the ligands is H2hypic ≫ HpicCN > Hprz > HpicFF, and this results in a different behavior at pH 7.40. In organic and aqueous solution the three isomers OC-6-23, OC-6-24, and OC-6-42 are formed, and this is confirmed by DFT simulations. In all the systems with apo-transferrin (VO)2(apo-hTf) is the main species in solution, with the hydrolytic VIVO species becoming more important with lowering the strength of the ligand. In the systems with albumin, (VO)xHSA (x = 5, 6) coexists with VOL2(HSA) and VOL(HSA)(H2O) when L = picCN, prz, with [VO(Hhypic)(hypic)]−, [VO(hypic)2]2–, and [(VO)4(μ-hypic)4(H2O)4] when H2hypic is studied, and with the hydrolytic VIVO species when HpicFF is examined. Finally, the consequence of the hydrolysis on the binding of VIVO2+ to the blood proteins, the possible uptake of V species by the cells, and the possible relationship with the insulin-enhancing activity are discussed

A tri-functional vanadium(IV) complex to detect cysteine oxidation

The development of effective molecular probes to detect and image the levels of oxidative stress in cells remains a challenge. Herein we report the design, synthesis and preliminary biological evaluation of a novel optical probe to monitor oxidation of thiol groups in cysteine-based phosphatases (CBPs). Following orthogonal protecting approaches we synthesised a new vanadyl complex designed to bind to CBPs. This complex is functionalised with a well-known dimedone derivative (to covalently trap sulfenic acids, SOHs) and a coumarin-based fluorophore for optical visualization. We show that this new probe efficiently binds to a range of phosphatases in vitro with nanomolar affinity. Moreover, preliminary flow cytometry and microscopy studies in live HCT116 cells show that this probe can successfully image cellular levels of sulfenic acids – one of the species resulting from protein oxidative damage