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 ( N,N,N' ,N'-tetrakis(6-fluoro-2-quinolylmethyl)-2-hydroxy-1,3-propanediamine), and HT(8Q)HPN ( N,N,N' ,N'-tetrakis(8-quinolylmethyl)-2-hydroxy-1,3-propanediamine), 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 ( IPPi/ I0 = 12.5) and selectivity toward PPi sensing ( IATP/ IPPi = 20% and IADP/ IPPi = 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.

Fluorescent Detection of Phosphate Ion via a Tetranuclear Zinc Complex Supported by a Tetrakisquinoline Ligand and µ4-PO4 Core.

The tetrakisquinoline ligand HT(6-MeO8Q)HPN (N,N,N',N'-tetrakis(6-methoxy-8-quinolylmethyl)-2-hydroxy-1,3-propanediamine) exhibited Zn2+-induced fluorescence enhancement with high specificity and sensitivity (IZn/I0 = 57 and ICd/IZn = 6% in the presence of 2 equiv of Zn2+; LOD (limit of detection) = 15 nM). This ligand also exhibited fluorescence enhancement specific to inorganic phosphate (PO43-) in DMF-HEPES buffer (50 mM HEPES, 100 mM KCl, pH = 7.5) (1:1) in the presence of 2 equiv of Zn2+. The structure of the unprecedented tetranuclear zinc complex with a µ4-PO4 bridge was elucidated by X-ray crystallography as the key species responsible for fluorescence enhancement.

OFF-ON-OFF fluorescent response of N,N,N',N'-tetrakis(1-isoquinolylmethyl)-2-hydroxy-1,3-propanediamine (1-isoHTQHPN) toward Zn(2.).

An isoquinoline-based ligand, N,N,N',N'-tetrakis(1-isoquinolylmethyl)-2-hydroxy-1,3-propanediamine (1-isoHTQHPN), exhibits a fluorescence increase at 475 nm upon addition of 1 equiv. of Zn(2+) (IZn/I0 = 12, ϕZn = 0.023). This fluorescence enhancement turns and then decreases sharply after the addition of more than 1 equiv. of Zn(2+) reaching a constant minimum intensity with more than 2 equiv. of Zn(2+). In contrast, the fluorescence intensity at 353 nm continues to increase until the signal saturates at ca. 5 equiv. of Zn(2+). This observation can be explained by the formation of a fluorescent mononuclear complex ([Zn(1-isoHTQHPN)](2+)) followed by a non-fluorescent dinuclear complex ([Zn2(1-isoTQHPN)](3+)) at 475 nm during the titration of 1-isoHTQHPN with Zn(2+). Both the mono- and dinuclear complexes were characterized by UV-vis, fluorescence, (1)H NMR, ESI-MS, X-ray crystallography and TDDFT calculations. The fluorescence enhancement at 475 nm is Zn(2+)-specific; Cd(2+) induces a much smaller emission increase (ICd/I0 = 3.7, ICd/IZn = 31%). The Zn(2+)/Cd(2+) selectivity of the fluorescent response correlates with the difference in excimer-forming ability derived from the Cd-Nisoquinoline and Zn-Nisoquinoline bond distances.

Tris(8-methoxy-2-quinolylmethyl)amine (8-MeOTQA) as a highly fluorescent Zn(2+) probe prepared by convenient C3-symmetric tripodal amine synthesis.

A convenient synthesis of C3-symmetric tribenzylamine (TBA) derivatives has been investigated. The reaction of benzyl chlorides with acetaldehyde ammonia trimer () in the presence of base afforded tribenzylamines in high yields. This efficient method allows the diverse synthesis of TPA (tris(2-pyridylmethyl)amine) and TQA (tris(2-quinolylmethyl)amine) derivatives. Among the TQA compounds prepared, tris(8-methoxy-2-quinolylmethyl)amine (8-MeOTQA, ) exhibited superior properties as a fluorescent zinc probe with high quantum yield (ϕZn = 0.51) and high sensitivity (limit of detection (LOD) = 3.4 nM). The X-ray crystallographic analysis of [Zn(8-MeOTQA)](2+) revealed that the steric and electronic effect of 8-methoxy substituents kicks out the solvent and counterion molecules from the metal coordination sphere, resulting in short Zn-Nquinoline coordination distances (2.04-2.07 Å). The pseudo hexacoordinate complex of 6-methoxy derivative, [Zn(6-MeOTQA)(DMF)(ClO4)](+), exhibited longer Zn-Nquinoline distances (2.07-2.19 Å) and much smaller fluorescence intensity (ϕZn = 0.027). The replacement of one of the three 8-methoxyquinolines with pyridine also afforded much less fluorescent zinc complex (ϕZn = 0.095) due to the solvent coordination (Zn-Nquinoline = 2.05-2.18 Å for [Zn(8-MeOBQPA)(CH3OH)](2+)).

Quantitative fluorescent detection of pyrophosphate with quinoline-ligated dinuclear zinc complexes.

Dinuclear zinc complex [Zn2(TQHPN)(AcO)](2+) exhibits characteristic fluorescence response (λex = 317 nm and λem = 455 nm) toward pyrophosphate (PPi) with maximum fluorescence upon 1:1 Zn2(TQHPN)-PPi complex formation. The crystallographic investigation utilizing P(1)P(2)-Ph2PPi revealed that the fluorescent response mechanism is due to intramolecular excimer formation of two quinoline rings.