DNA Cleavage by New Oxovanadium(IV) Complexes of N-Salicylidene α-Amino Acids and Phenanthroline Bases in the Photodynamic Therapy Window

Abstract

Oxovanadium(IV) complexes [VO(salmet)(B)] (1-3) and [VO(saltrp)(B)] (4-6), where salmet and saltrp are N-salicylidene-l-methionate and N-salicylidene-l-tryptophanate, respectively, and B is a N,N-donor heterocyclic base (viz. 1,10-phenanthroline (phen, 1, 4), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 2, 5), and dipyrido[3,2-a:2',3'-c]phenazine (dppz, 3, 6)) are prepared and characterized and their DNA binding and photoinduced DNA cleavage activity studied. Complexes 1, 2, and 4 are structurally characterized by single-crystal X-ray crystallography. The molecular structure shows the presence of a vanadyl group in the VO3N3 coordination geometry. The dianionic alpha-amino acid Schiff base acts as a tridentate O,N,O-donor ligand in a meridional binding mode. The N,N-donor heterocyclic base displays a chelating mode of bonding with a N-donor site trans to the oxo group. The complexes show a d-d band in the range of 680-710 nm in DMF with a shoulder near 840 nm. They exhibit an irreversible oxidative cyclic voltammetric response near 0.8 V assignable to the V(V)/V(IV) couple and a quasi-reversible V(IV)/V(III) redox couple near -1.1 V vs SCE in DMF-0.1 M TBAP. The complexes show good binding propensity to calf thymus DNA giving binding constant values in the range from 5.2 x 10(4) to 7.2 x 10(5) M(-1). The binding site size, thermal melting, and viscosity data suggest DNA surface and/or groove binding nature of the complexes. The complexes show poor "chemical nuclease" activity in the dark in the presence of 3-mercaptopropionic acid or hydrogen peroxide. The dpq and dppz complexes show efficient DNA cleavage activity on irradiation with UV-A light of 365 nm via a mechanistic pathway involving formation of singlet oxygen as the reactive species. They also show significant DNA cleavage activity on photoexcitation in red light (>750 nm) by (1)O2 species. Observation of red-light-induced cleavage of DNA is unprecedented in the vanadium chemistry. The DNA cleavage activity is metal promoted as the ligands or vanadyl sulfate alone are cleavage inactive on photoirradiation at these wavelengths.

Coordination Polymers and Metal Organic Frameworks Derived from 1,2,4-Triazole Amino Acid Linkers

“…were also conducted because of their various binding and bridging modes [26][27][28][29][30][31][32][33]. Not surprisingly, in a short course, biomolecules and natural products like amino acids [34][35][36][37][38][39][40][41][42][43][44][45][46], peptides [47], proteins [46], nucleobases [48], magnesium formates [49], carbohydrates [47], metal glutarates [50,51], γ-cyclodextrin [36] leaped into this mainstream as attractive precursors and soon tributaries like metal-peptide frameworks (MPFs) [47], metal-biomolecule frameworks (MBioFs) [46][47][48] surfaced out and established their niche.…”

“…Among them the perceptible appearance of amino acid derivatives in recent years, either as metal-based molecular entities or oligomeric scaffolds in MOFs or CPs, justify their inclusion in the synthon/tecton library [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48]. In this frame, structure and reactivity of different amino acids in their natural or derivatized form were extensively studied.…”

“…In this frame, structure and reactivity of different amino acids in their natural or derivatized form were extensively studied. Relevant examples include proline [34,35], glycine [34], valine [36], alanine [37], aspartic acid [38], glutamic acid [36], phenyl alanine [39], histidine [40], methionine [41][42][43][44] and typtophan [36][37][38][39][40][41][42][43][44][45].…”

“…Advantages of amino acids are their natural framework with rich functional groups, which is amenable to derivatization thereby offering intriguing topologies when inserted as building blocks in supramolecular hierarchical self-assemblies [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51]. Indeed, thanks to their genuine chirality (except glycine) and electronic asymmetry, amino acid derivatives are considered as a preeminent choice to introduce asymmetry in MOFs to direct the network construction.…”

Oxidative DNA cleavage, cytotoxicity and antimicrobial studies of l-ornithine copper (II) complexes

“…The strong binding affinity of the copper bis phen complex and the redox behavior of the copper center play an important role in inducing oxidative DNA cleavage. Chakravarty and co-workers recently explored amino acid transition metal based chemistry towards cleavage of DNA under physiological conditions by oxidative as well as photochemical means on charge transfer or d-d band excitation [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. The copper complex of L-lysine structure is closely resembles the copper-ornithine structure, which shows efficient chemical nuclease activity [25].…”