Water‐Soluble Heteronuclear [NaCuII6] Metallomacrocyclic Sandwich Complexes: Synthesis, Structure, Properties and In Vitro Biological Studies

Abstract

AbstractThe water‐soluble heteronuclear metallomacrocyclic sandwich clusters [NaCu6(hpnbpda)3(OH)3(OH2)3](NO3)·4H2O (1), [NaCu6(hpnbpda)3(OH)3(OH2)3](ClO4) (2), and [NaCu6(hpnbpda)3(OH)3(OH2)3](PF6) (3) [H3hpnbpda = N,N′‐bis(2‐pyridylmethyl)‐2‐hydroxy‐1,3‐propanediamine‐N,N′‐diacetic acid] have been synthesized in methanol at room temperature and fully characterized using several analytical techniques including single‐crystal X‐ray diffraction. The molecular architecture of complex 1 is built from the template assembly of three dinuclear [Cu2(hpnbpda)]+ fragments through their weak oxophillic interactions with a central sodium(I) cation. A close analysis of the single‐crystal X‐ray structure reveals that the metallic core of cluster 1 consists of six highly distorted octahedral CuII ions arranged at the corners of a trigonal prism that encapsulates the sodium(I) ion. Complex 1 displays a rare μ3:η2:η1:η1 bridging mode of six carboxylate groups of three hpnbpda3– ligands with each bridging between two copper(II) atoms and the sodium(I) center. Variable‐temperature magnetic‐susceptibility measurements (2–300 K) on a powdered microcrystalline sample reveal that the paramagnetic copper centers in complex 1 are antiferromagnetically coupled to one another. Systematic biological investigation such as cytotoxicity assessment, DNA content analysis in terms of cell‐cycle distribution by means of the fluorescence‐activated cell sorting (FACS) method, DNA binding, DNA cleavage, and the underlying mechanism of possible apoptotic cell‐death events in human cervical cancer cells (HeLa) were carried out in detail using complex 1. The in vitro assays using complex 1 in HeLa cells provided new findings that indicate its possible future therapeutic application. Theoretical calculations were carried out to find the Fukui functions at the metal sites in complex 1 to predict the possible metal centers involved in the DNA binding.