title: Design and Synthesis of Functional Molecules Based on Complexation and Their Biological Applications.
abstract: In this review, we introduce the development of supermolecules, host-guest complexes, and metal complexes formed from the combination of non-covalent interactions and/or coordination bonds, as well as their biological applications. An adenine selective host molecule 1 provides a correctly oriented array of complementary hydrogen bonding sites for the adenine nucleobase. Furthermore, the new DDAA (D: hydrogen bond donor, A: hydrogen bond acceptor) module 4 and ADDA module 7 have been developed as quadruple hydrogen-bonding modules. A quadruple zwitterion 8 forms supramolecular gel in dimethyl sulfoxide, driven by the formation of ion-paired dimers between the zwitterionic units. The obtained supramolecular gel exhibits reversible gel-sol transitions in response to both acid, base, and heating. Self-assembly of a dimeric zinc(II) complex, dianion of cyanuric acid (CA) or 5,5-diethylbarbituric acid (Bar), and copper(II) ion (Cu2+) in an aqueous solution provides 4 : 4 : 4 and 2 : 2 : 2 supermolecules 10 and 11, respectively. These supermolecules possess Cu2(μ-OH)2centers, and accelerate the hydrolysis of a phosphate monoester dianion, mono(4-nitrophenyl)phosphate (MNP), at neutral pH. Regioselective substitution reactions of tris-cyclometalated iridium (Ir) complexes at the 5'-position on 2-phenylpyridine type ligands, and their subsequent conversions to a variety of functional groups are described. For example, pH-sensitive Ir complexes having basic functional groups have been developed. Tris-cyclometalated Ir complexes containing cationic peptides, such as Lys-Lys-Gly-Gly (KKGG) peptides, work as inducers and detectors of cancer cell death. Mechanistic studies suggest that the Ir complex interacts with anionic molecules on the cell surface and/or membrane receptors to trigger an intracellular Ca2+response, resulting in necrosis accompanied by membrane disruption.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Hisamatsu
mesh_terms: D000225:Adenine / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents; D001665:Binding Sites; D001695:Biology; D016923:Cell Death / Q000187:drug effects; D002614:Chelating Agents / Q000737:chemistry* / Q000494:pharmacology; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D003300:Copper / Q000737:chemistry; D015195:Drug Design; D005782:Gels; D006801:Humans; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D049449:Luminescence; D046911:Macromolecular Substances; D051379:Mice; D015394:Molecular Structure; D009369:Neoplasms / Q000473:pathology; D044367:Phase Transition; D014227:Triazines / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D002614:Chelating Agents; D056831:Coordination Complexes; D005782:Gels; D046911:Macromolecular Substances; D014227:Triazines; D003300:Copper; C004632:cyanuric acid; D015032:Zinc; D000225:Adenine