Pyrophosphate-Induced Intramolecular Excimer Formation in Dinuclear Zinc(II) Complexes with Tetrakisquinoline Ligands

Dinuclear Zn2+ complexes with HTQHPN (N,N,N',N'tetrakis(2-quinolylmethyl)-2-hydroxy-1,3-propanediamine) derivatives have been prepared, and their pyrophosphate (PPi, P2O74-) sensing properties were examined. The ligand library includes six HTQHPN derivatives with electron-donating/withdrawing substituents, an extended aromatic ring, and six-membered chelates upon zinc binding. Complexation of ligand with 2 equiv of Zn2+ promotes small to moderate fluorescence enhancement around 380 nm, but in the cases of HTQHPN, HT(6-FQ)HPN tetrakis(6-fluoro-2-quinolylmethyl)-2-hydroxy-1,3-propanediamine), and HT (8 HPN (N,N,N',N'-tetrakis(8-quinolylmethyl) -2-hydroxy-1,3-propan ediamine), subsequent addition of PPi induced a significant fluorescence increase around 450 nm. This fluorescence enhancement in the long wavelength region is attributed to the conformational change of the bis-(quinolylmethyl)amine moiety which promotes intramolecular excimer formation between adjacent quinolines upon binding with PPi. The structures of PPi- and phosphate-bound dizinc complexes were revealed by X-ray crystallography utilizing phenyl-substituted analogues. The zinc complex with HT(8Q)HPN exhibits the highest signal enhancement (Ipp,/I-0 = 12.5) and selectivity toward PPi sensing ( N(I-ATP/I-PPi = 20% and I-ADp/I-ppi = 25%). The fluorescence enhancement turned to decrease gradually after the addition of more than 1 equiv of PPi due to the removal of zinc ion from the ligand-zinc-PPi ternary complex, allowing the accurate determination of PPi concentrations at the fluorescence maximum composition. The practical application of the present method was demonstrated monitoring the enzymatic activity of pyrophosphatase.