Synthesis and structural characterization of dioxomolybdenum and dioxotungsten hydroxamato complexes and their function in the protection of radiation induced DNA damage

Abstract

The synthesis and structural characterization of two novel dioxomolybdenum(VI) (1) and dioxotungsten(VI) (2) complexes with 2-phenylacetylhydroxamic acid (PAHH) [M(O)2(PAH)2] [M = Mo, W] have been accomplished. The dioxomolybdenum(VI) and dioxotungsten(VI) moiety is coordinated by the hydroxamate group (-CONHO(-)) of the 2-phenylacetylhydroxamate (PAH) ligand in a bi-dentate fashion. In both the complexes the PAHH ligand is coordinated through oxygen atoms forming a five membered chelate. The hydrogen atom of N-H of the hydroxamate group is engaged in intermolecular H-bonding with the carbonyl oxygen of another coordinated hydroxamate ligand, thereby forming an extended 1D chain. The ligand as well as both the complexes exhibit the ability to protect from radiation induced damage both in CTDNA as well as in pUC19 plasmid DNA. As the damage to DNA is caused by the radicals generated during radiolysis, its scavenging imparts protection from the damage to DNA. To understand the mechanism of protection, binding affinities of the ligand and the complex with DNA were determined using absorption and emission spectral studies and viscosity measurements, whereby the results indicate that both the complexes and the hydroxamate ligand interact with calf thymus DNA in the minor groove. The intrinsic binding constants, obtained from UV-vis studies, are 7.2 × 10(3) M(-1), 5.2 × 10(4) M(-1) and 1.2 × 10(4) M(-1) for the ligand and complexes 1 and 2 respectively. The Stern-Volmer quenching constants obtained from a luminescence study for both the complexes are 5.6 × 10(4) M(-1) and 1.6 × 10(4) M(-1) respectively. The dioxomolybdenum(VI) complex is found to be a more potent radioprotector compared to the dioxotungsten(VI) complex and the ligand. Radical scavenging chemical studies suggest that the complexes have a greater ability to scavenge both the hydroxyl as well as the superoxide radicals compared to the ligand. The free radical scavenging ability of the ligand and the complexes was further established by EPR spectroscopy using a stable free radical, the DPPH, as a probe. The experimental results of DNA binding are further supported by molecular docking studies.

Rare Examples of Biomimicking Molybdenum(VI) Catalysed Peroxidative Bromination of the Organic Substrates that Coordinate to the Oxido‐Diperoxido Mo(VI) Centre

“…The vibration frequencies of ν Mo‐O appear at 957 and 960 cm −1 in the complexes 1 and 2 respectively. The IR stretching frequency of ν O‐O in the complexes 1 and 2 appear at 862 and 872 cm −1 respectively indicating the formation of peroxide linkage in both the complexes . The stretching frequencies appeared at 644 and 582 cm −1 in 1 and 655 and 585 cm −1 in 2 are assignable to asymmetric and symmetric vibrations respectively of the MoO 2 triangle formed from terminally coordinated O 2 −2 ligand …”

“…The C=O stretching band at 1627 cm −1 in the free 2‐hydroxyphenyl(phenyl)methanone ligand is shifted to 1624 and 1623 cm −1 in the complexes 1 and 2 respectively after coordination with the metal. These downward shifts occur due to the drainage of the electron density from C=O moiety to the metal centre during complexation . The vibration frequencies of ν Mo‐O appear at 957 and 960 cm −1 in the complexes 1 and 2 respectively.…”

Evaluation of the safety profile and antioxidant activity of fatty hydroxamic acid from underutilized seed oil of Cyperus esculentus

“…The design and synthesis of oleochemicals from biomass for industrial applications in fields such as Biomedical Sciences has been of great importance [33] . FHA falls into this group of oleochemicals with tremendous industrial applications which may be attributed to its expected reactivity, low toxicity and wide spectrum of activities in biological systems [34,35] . From the present study, FHA was synthesized from C. esculentus seed oil with the yield of FHA being 94%.…”

Appraisal of biochemical classes of radioprotectors: evidence, current status and guidelines for future development

“…The Hoechst minor groove ligands H33258 (C 25 H 24 N 6-OÁ3HCl), H33342 (C 27 H 28 N 6 OÁ3HCl) and amino derivatives methylproamine had protected V79 cells from radiation-induced DNA damage and death with a DMF of 2.1 (Martin et al 2004). Also, dioxomolybdenum and dioxotungusten hydroxamato had protected DNA from radiation-induced strand breaks (Paul et al 2014). Netropsin (C 18 H 26 N 10 O 3 Á2HCl), which is another minor groove binding ligand, had radioprotective properties through DNA structural stability mechanism (Mishra et al 2009).…”