Synthesis and structural characterization of Zn(II)–chrysin-phen complexes with tunable coordination architectures and notable antitumor activity

Three new Zn(II) coordination compounds derived from chrysin and 1,10-phenanthroline were synthesized using microwave-assisted methodology: a mononuclear complex ( 1 ), a two-dimensional coordination polymer ( 2 ), and a tetranuclear cluster ( 3 ). Fine-tuning of reaction parameters enabled selective access to these distinct architectures, with single-crystal X-ray diffraction confirming the structures of 1 and 3 . Positive-ion nanospray mass spectrometry showed that complexes 1 and 2 predominantly generate well-defined mononuclear Zn–chry–phen units upon ionization, a behavior consistent with the formation of such units under the experimental conditions, whereas cluster 3 undergoes extensive fragmentation into Zn–phen-based dicationic species, limiting biological evaluation to complexes 1 and 2 . Both compounds displayed enhanced, though moderate, radical-scavenging activity relative to free chrysin, consistent with electronic modulation and stabilization of phenoxyl radicals upon metal coordination. Their anticancer properties were assessed in vitro against human melanoma (A375), hepatocellular carcinoma (HepG2), and non-tumoral keratinocyte (HaCaT) cell lines. Complexes 1 and 2 exhibited pronounced time- and dose-dependent cytotoxicity, with IC 50 values in A375 and HepG2 markedly lower than those of free chrysin and comparable to phen. Cytotoxicity in HaCaT keratinocytes occurred within the same micromolar range, indicating modest selectivity while still providing meaningful insight into the biological behavior of Zn(II)–chrysin–phen systems. Mechanistic studies indicated S phase cell cycle arrest and increased reactive oxygen species (ROS) generation, suggesting oxidative stress as a key contributor to cytotoxicity against the tumor cell-lines. Overall, these findings highlight the versatility of microwave-assisted synthesis for generating structurally diverse Zn(II)–flavonoid architectures and advance understanding of their coordination chemistry and structure–activity relationships. • MWAS yields three distinct Zn(II)–chrysin–phen complexes. • Reaction control enables selective crystalline architectures. • Complexes 1–2 form stable mononuclear Zn–chry–phen units. • Complexes 1–2 show notable cytotoxicity in cancer cell lines. • ROS increase and S phase arrest drive cytotoxic effects.