Syntheses, crystal structures, theoretical studies, and anticancer properties of an unsymmetrical schiff base ligand N-2-(6-methylpyridyl)-2-hydroxy-1-naphthaldimine and its Ni(II) complex

• Published in: Journal of molecular structure 2022-12, Vol.1269, p.133717, Article 133717
• Main Authors: Bhattacharjee, Tirtha, Adhikari, Suman, Sheikh, Afzal Hussain, Mahmoudi, Ghodrat, Mlowe, Sixberth, Akerman, Matthew P, Choudhury, Nurul Alam, Chakraborty, Surajit, Butcher, Raymond J., Kennedy, Alan R., Demir, Burcu Saygıdeğer, Örs, Aylin, Saygideger, Yasemin
• Format: Article
• Language: English
• Subjects: Anticancer; DFT; Hirshfeld surface; Hydrogen bond; Schiff base; Supramolecular architecture
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.133717

•The Schiff-base ligand, N-2-(6-methylpyridyl)-2-hydroxy-1-naphthaldimine (1) and its hitherto unknown chelate from Ni(II) salt, bis[N-2-(6-methylpyridyl)-2-oxo-1-naphthaldimnato-k3N^N^O] nickel(II) (2) have been reported.•X-ray diffraction study shows zwitter ionic keto-amine tautomer form of planar Schiff base 1 that crystallizes in orthorhombic crystal system (space group Pbca) and exists as stacked column of dimeric segments in 3D formed by C13 ̶ H13A···O1i hydrogen bonds.•While the chelate 2 crystallizes in monoclinic crystal system, (space group I2/a) and the NiN4O2 coordination kernel adopts distorted octahedral geometry around Ni+2 center.•The anticancer activity of 1 and 2 has been investigated using cytotoxicity measure (MTT assay), apoptosis assay, quantitative polymerase chain reaction (qPCR), and colony formation assays.•The Ni(II) metal complex 2, demonstrated dose-dependent cytotoxicity in vitro, killing A549 lung cancer cells via an apoptotic pathway. In this work, syntheses of Schiff-base ligand, N-2-(6-methylpyridyl)-2-hydroxy-1-naphthaldimine (1) and its hitherto unknown chelate with a Ni(II) salt, bis[N-2-(6-methylpyridyl)-2-oxo-1-naphthaldimnato-k3N^N^O] nickel(II) (2) have been reported and characterized by spectral techniques (IR, 1H NMR, Mass). Solid state structures and non-covalent interactions persisting in 1 and 2 are studied by Density Functional Theory (DFT) optimizations and Hirshfeld Surface (HS) analysis. X-ray diffraction (XRD) study shows zwitter ionic keto-amine tautomer form of planar Schiff base 1 that exists as dimer formed by C13 ̶ H13A···O1i [(i) -x+1, -y, -z+1] hydrogen bonds and distorted octahedral geometry around Ni+2 center in chelate 2, where overall crystal structure stability may be attributed to weak C ̶ H···π, π···π stacking, van der Waals interactions, and C ̶ H···O type intermolecular hydrogen bonds. The HS study and 2D Finger Print (FP) plots corroborate well with XRD data and show prominent O···H/H···O spikes (2.2 Å < de+di < 2.3 Å) and C···H/H···C (2.5 Å < de+di < 2.6 Å) spikes that arise from C ̶ H···O type H-bonds and C ̶ H···π interactions respectively, along with significant C···C interactions (de+di ∼ 3.3 Å) due to π···π stacking (2). The anticancer activity has been investigated by using cytotoxicity measure (MTT assay), apoptosis assay, quantitative polymerase chain reaction (qPCR), and colony formation assays. The Ni(II) metal complex demonstrates dose-dependent cytotoxicity in vitro, killing