title: A luminescence sensor of inositol 1,4,5-triphosphate and its model compound by ruthenium-templated assembly of a bis(Zn2+-cyclen) complex having a 2,2'-bipyridyl linker (cyclen = 1,4,7,10-tetraazacyclododecane).
abstract: A new supramolecular complex (Ru(Zn2L4)3) was designed and synthesized as a luminescence sensor for inositol 1,4,5-triphosphate (IP3), which is one of the important second messengers in intracellular signal transduction, and its achiral model compound, cis,cis-1,3,5-cyclohexanetriol triphosphate (CTP3), by a ruthenium(II)-templated assembly of three molecules of a bis(Zn2+-cyclen) complex having a 2,2-bipyridyl linker (Zn2L4). Single-crystal X-ray diffraction analysis of a racemic mixture of Ru(Zn2L4)3 showed that three of the six Zn2+-cyclen units are orientated to face the opposite side of the molecule with three apical ligands (Zn2+-bound HO-) of each of the three Zn2+ located on the same face. 1H NMR and UV titrations of Ru(Zn2L4)3 with CTP3 indicated that Ru(Zn2L4)3 forms a 1:2 complex with CTP3, (Ru(Zn2L4)3)-((CTP3)6-)2, in aqueous solution at neutral pH. In the absence of guest molecules, Ru(Zn2L4)3 (10 microM) has an emission maximum at 610 nm at pH 7.4 (10 mM HEPES with I = 0.1 (NaNO3)) and 25 degrees C (excitation at 300 nm). An addition of 2 equiv of CTP3 induced a 4.2-fold enhancement in the emission of Ru(Zn2L4)3 at 584 nm. In this article, we describe that Ru(Zn2L4)3 is the first chemical sensor that directly responds to CTP3 and IP3 and discriminates these triphosphates from monophosphates and diphosphates. The photodecomposition of Ru(Zn2L4)3, which is inhibited upon complexation with CTP3, and the stereoselective complexation of chiral IP3 by Ru(Zn2L4)3 are also described.
authors.affiliation: Faculty of Pharmaceutical Sciences and Center for Drug Delivery Research, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510 Japan. shinaoki@rs.noda.tus.ac.jp
authors.forename: Shin
authors.initials: S
authors.lastname: Aoki
authors.forename: Mohd
authors.initials: M
authors.lastname: Zulkefeli
authors.forename: Motoo
authors.initials: M
authors.lastname: Shiro
authors.forename: Masanori
authors.initials: M
authors.lastname: Kohsako
authors.forename: Kei
authors.initials: K
authors.lastname: Takeda
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kimura
mesh_terms: D003510:Cyclohexanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000528:radiation effects; D006863:Hydrogen-Ion Concentration; D015544:Inositol 1,4,5-Trisphosphate / Q000138:chemical synthesis* / Q000737:chemistry / Q000528:radiation effects; D008163:Luminescent Measurements; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000528:radiation effects; D010710:Phosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000528:radiation effects; D012428:Ruthenium / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013997:Time Factors; D014466:Ultraviolet Rays; D014961:X-Ray Diffraction; D015032:Zinc / Q000737:chemistry*
chemical_list: D003510:Cyclohexanes; D009942:Organometallic Compounds; D010710:Phosphates; C504864:cis,cis-1,3,5-cyclohexanetriol triphosphate; D012428:Ruthenium; D015544:Inositol 1,4,5-Trisphosphate; D015032:Zinc