Photolability of NO in ruthenium nitrosyls with pentadentate ligand induces exceptional cytotoxicity towards VCaP, 22Rv1 and A549 cancer cells under therapeutic condition

Kumbhakar, Sadananda and Gupta, P. and Giri, Bishnubasu and Muley, Arabinda and Karumban, K.S. and Misra, Ashish and Maji, Somnath (2022) Photolability of NO in ruthenium nitrosyls with pentadentate ligand induces exceptional cytotoxicity towards VCaP, 22Rv1 and A549 cancer cells under therapeutic condition. Journal of Molecular Structure, 1265. pp. 1-15. ISSN 0022-2860

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Pentadentate electron rich MePBITA ligand in [RuII(MePBITA)(NO)]n+ (n = 3, 2 and MePBITA = 1-(6-(1-methyl-1H-benzo[d]imidazol-2-yl)pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine) permits the isolation of both the redox states of nitrosyls with Enemark–Feltham notation {RuNO}6 and {RuNO}7. The nitrosyl derivative [RuII(MePBITA)(NO)](ClO4)3: [4](ClO4)3 was synthesized by stepwise synthetic manner from the chloro precursor [RuII(MePBITA)(Cl)](PF6): [1](PF6), via the acetonitrile derivative [RuII(MePBITA)(CH3CN)](PF6)2: [2](PF6)2 followed by nitro complex [RuII(MePBITA)(NO2)](PF6): [3](PF6). All the complexes were fully characterized by different analytical and spectroscopic techniques. Single crystal X-ray structures of the complexes [1](PF6), [2](PF6)2, [3](PF6), and [4](ClO4)3 were profitably determined for understanding the molecular integrity. Ru−NO stretching frequency observed at 1931 cm−1 for [4](ClO4)3 suggests a moderately electrophilic character of NO. The huge shift in νNO frequency, Δν (solid) = 325 cm−1 was observed by reducing [4](ClO4)3 to [4](ClO4)2. The conversion of [3]+ from [4]3+ was examined both electrochemically and spectrophotometrically with the addition of 0.5 M NaOH solution. Rate constants of the first order photorelease (kNO) have been found to be 8.99 × 10−3 min−1; half-life (t1/2) = 77 min and 3.84 × 10−2 min−1; half-life (t1/2) = 18 min for [4]3+ and [4]2+, respectively with visible Xenon light (200 W) source. The photo liberated NO has been scavenged by biologically relevant target protein reduced myoglobin as Mb−NO adduct. Photoactivation of [4]3+ and [4]2+ by visible light induces significant cytotoxicity in prostate cancer cell lines; VCaP (IC50 29.74 and 4.42 µM) and 22Rv1 (IC50 29.96 and 6.88 µM), and lung cancer cell line; A549 (IC50 2.24 and 0.12 µM). Collectively our results pave the way for the development of metallodrugs as potential therapeutics for a variety of cancers. Additionally, our results also demonstrate how ligand modification could enhance the photolability of metal nitrosyl, adding a new dimension for future efficient photoactive metal nitrosyl design. © 2022 Elsevier B.V.

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IITH Creators:
IITH CreatorsORCiD
Maji, Somnath
Item Type: Article
Additional Information: Financial support received from SERB, project no. ECR/2016/000382 (Somnath Maji and fellowship to S.K.), Council of Scientific and Industrial Research (CSIR) (fellowship to B.G., A.M. and K.S.) and IIT Hyderabad are gratefully acknowledged for the financial support. S.K. and P.G. acknowledge fellowship support from MoE. Ashish Misra acknowledges financial support from SERB (project no. ECR/2017/002544).
Uncontrolled Keywords: Anticancer activity, Crystal structures, Electrochemistry, In vitro cytotoxicity, Photo release, Redox-active ligand, Ruthenium nitrosyls
Subjects: Others > Biotechnology
Divisions: Department of Chemistry
Depositing User: . LibTrainee 2021
Date Deposited: 17 Jun 2022 10:01
Last Modified: 17 Jun 2022 10:42
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