In-depth synthetic, physicochemical and in vitro biological investigation of a new ternary V(IV) antioxidant material based on curcumin

Abstract

Curcumin is a natural product with a broad spectrum of beneficial properties relating to pharmaceutical applications, extending from traditional remedies to modern cosmetics. The biological activity of such pigments, however, is limited by their solubility and bioavailability, thereby necessitating new ways of achieving optimal tissue cellular response and efficacy as drugs. Metal ion complexation provides a significant route toward improvement of curcumin stability and biological activity, with vanadium being a representative such metal ion, known for its presence in biological systems and its exogenous biological activity in potential pharmaceuticals. Driven by the need to optimally increase curcumin bioavailability and bio-activity through complexation, synthetic efforts were launched to seek out stable species, ultimately leading to the synthesis and isolation of a new ternary V(IV)-curcumin-(2,2'-bipyridine) complex. Physicochemical characterization (elemental analysis, FT-IR, TGA, UV-Visible, NMR, ESI-MS, Fluorescence, X-rays) portrayed the solid-state and solution properties of the ternary complex. Pulsed EPR spectroscopy, in frozen solutions, suggested the presence of two species, cis-and trans-conformers. DFT calculations revealed the salient features and energetics of the two conformers, thereby complementing EPR spectroscopy. The well-described profile of the vanadium species led to its in vitro biological investigation involving toxicity, cell metabolism inhibition in cultures of S. cerevisiae, ROS-suppressing capacity, lipid peroxidation, and plasmid DNA degradation. A multitude of bio-assays and methodologies in comparison to free curcumin, showed that it exhibits its antioxidant potential in a concentration-dependent fashion, thereby formulating a bioreactivity profile supporting development of new potentially efficient hybrid vanado-pharmaceuticals, targeting (extra)intra-cellular processes under (patho)physiological conditions.

Zn(II) Curcuminate Complexes with 2,2′-bipyridine and Carboxylates

“…In a dinuclear [Zn 2 (tpy)(acac) 4 ] with a O 4 N donor set defining a trigonal bipyramidal environment, the acac-to-zinc bond lengths span a wider interval, 1.966(2)–2.089(2) Å, whereas the bite angles are 88.39(6)–90.42(8)° [45]. In all known structures of the curcuminate metal complexes, the ligand adopts a chelating bidentate O,O-donor coordination mode with the curcuminate-to-metal bonds depending upon the nature of the metal ion [21,22,26,36,39,46,47,48,49,50,51]. For example, the La–O bond distances involving the cur − ligand in [La(R-tpy)(cur)(NO 3 ) 2 ] (R-tpy = 4’-phenyl-2,2′:6’,2″-terpyridine) are as long as 2.400(4) and 2.410(4) Å [22].…”

“…The variation of ligand types and their steric effect around the metal center is an essential parameter for modulating (tuning) the solubility, stability, and biological activities of metal complexes. In some studies, bipyridine derivatives have proven to be suitable spectator ligands to complete the metal ion coordination sphere along with cur − , and thereby improve the crystallization of the complex [36,39,40]. Acetate ions in Pt(II) complexes were shown to significantly enhance their solubility in water and chemical stability compared to the parent chlorides, while a benzoate ligand in a kiteplatin Pt(IV) analog has boosted its cytotoxicity [41,42].…”

Magnetic cationic liposomal nanocarriers for the efficient drug delivery of a curcumin-based vanadium complex with anticancer potential

“…The complex [VO(C21H19O6)(C10H8N2)(H2O)]2(SO4).2CH3OH.3H2O (VCur) (Fig. 1) was prepared and fully characterized according to previously reported work [36].…”

“…In the present work, the third crystallographically reported oxovanadium(IV) complex of curcumin (VCur) (Fig. 1) with significant anti-ROS/anti-oxidant activity and DNA degradation potential [36] is encapsulated for the first time in magnetic cationic liposomal nanocarriers in the effort to create novel nanoformulations with targeted anticancer activity based on metal complexes of bioactive natural polyphenols.…”

“…With the hope that investigation of the homogeneous dispersion and encapsulation of hydrophobic anticancer metal ion complexes in magnetic cationic liposomes (MCLPs) will enable development of new multifunctional pharmaceutical nanomaterials with enhanced bioavailability and targeted antitumor activity, this work for the first time a) evaluates and compares the anticancer efficiency and DNA-binding capacity of a crystallographically defined ternary V(IV)-curcumin-bipyridine complex (VCur) with proven bioactive efficacy [36] (Fig. 1), b) leads to the synthesis of citric acid (CA) surface-modified monodispersed magnetite (Fe3O4-CA) colloidal magnetic NPs (MNPs), c) develops MCLPs (mentioned henceforth as empty MCLPs, EMCLPs) via the thin film hydration method, d) evaluates and compares the suitability of these magnetic cationic liposomal vesicles as potential nanocarriers of VCur, (mentioned henceforth as VCur-loaded MCLPs, VCMCLPs), and e) investigates structural and textural properties of the encapsulated material through different and complementary characterization techniques.…”