Synthesis, Crystal Structure And Property Of Ferrocenyl N-heterocyclic Complexes

Among the numerous ferrocene complexes,a great number of therapeatic agents with the incorporating ferrocene as pharmacophore on the scaffold of biologically active N-heterocyclic molecule have been found to be promising antitumor candidates.Both N-heterocyclic imidazole and pyrazole substituent have good biological activity.The electron rich imidazole heterocycle has good donor character,it's found that good anticancer activity of complexes would be achieved by imidazolyl-ferrocene ligand.Pyrazole,belonging to one such N-heterocyclic ring,is also valuable core for the design and synthesis of compounds with outstanding anticancer activities.Exploring the combined influence of pyrazole on redox-activity and biological property of ferrocene in a single hybrid molecule will be considerably significant.Complex 1([Mn(C₁₆H₁₆FeN₂O₂)₄?H₂O?₂]Cl₂)and 2([Co(C₁₆H₁₆FeN₂O₂)₄?H₂O?₂]?NO₃?₂·3H₂O)based on imidazolyl-ferrocene ligand were obtained under convenient solvothermal conditions.During the assemble process of 3D supramolecular architectures,complex1 was dominated by non-classical C-H???O hydrogen bonds while 2 was assembled by both classical O-H???O hydrogen bonds and C-H???O hydrogen bonds.Different from chloride ions only balanced the electric charge in 1,nitrate anions in 2 not only balanced the electric charge but also contributed largely to stability through O-H???O hydrogen bonds.Electrochemical investigation showed that both 1 and 2 displayed anticipated one-electron redox process of the ferrocenyl group.Moreover,complex 2had better redox reversibility than 1.It's significant to reveal the detailed structural and electrochemical characters of these kind of ferrocene-containing complexes for the further application on areas of anticancer metallodrugs.Three synthesized water-soluble ferrocene complexes based on pyrazolyl-ferrocene ligand([Ni(C₂₂H₁₄F₆FeN₄O₄)?H₂O?₄]?5a?,[Mg(C₂₂H₁₄F₆FeN₄O₄)?H₂O?₄]·3H₂O?5b?,and[Ba(C₂₂H₁₄F₆FeN₄O₄)?H₂O?₃]?5c?),which acted as anticancer drugs,have been successfully encapsulated in silica by facile inverse-microemulsion method to form the multifunctional nanospheres?WFCs@SiO₂ and WFCs@SiO₂@glutaraldehyde?GA??,thereby changing drug delivery mode and protecting them from the adverse environments in physiological conditions.The drug-loading capacities of 5a,5b,and5c in WFCs@SiO₂ were found to be 38.4,38.2,and 38.1?g/mg,respectively.In particular,the obtained WFCs@SiO₂ nanospheres was further surface modified with GA.Compared to WFCs@SiO₂,the modification of GA on the spherical surface provided not only the better water-dispersity but also more functional groups.Finally,a series of cell studies under two different drug delivery modes?free diffusion and endocytosis?was carried out on their cytotoxicity by MTT cell-survival assays.Notably,both 5a and 5c delivered by silica-encapsulated nanospheres displayed remarkably cytotoxicity.With the use of this novel nanocarrier system in WFCs investigation,a variety of water-soluble drugs can also be encapsulated in silicon nanospheres.It is significant for developing more novel metal-based anticancer drugs by further modification of other pharmacophores in tumor therapy.