A new fluorescent sensor for zinc that binds 1 equivalent of zinc ion, N,N,N′,N′-tetrakis(2-quinolylmethyl)ethylenediamine (TQEN), has been prepared and characterized. Zinc-bound TQEN exhibits fluorescence around 383 nm upon excitation at 317 nm, while free TQEN emits very weak fluorescence. UV-Vis and ¹H NMR spectral changes also detected the binding of TQEN with zinc ion. The crystal structure of zinc complex with TQEN was determined by X-ray crystallography and compared with that of the TPEN–Zn complex (TPEN = N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine). The binding affinity of TQEN with zinc ion is very high (K_d < 1 µM in aqueous dmf solution). Competition experiments reveal that the zinc-binding affinity of TQEN is lower than the parent, strong metal ion chelator TPEN, and comparable to EGTA (EGTA = ethylene glycol-bis(2-aminomethyl)-N,N,N′,N′-tetraacetic acid).

Several bisquinoline derivatives, N,N′-bis(2-quinolylmethyl)-N,N′-dialkylethylnediamines (alkyl = methyl, ethyl, isopropyl and t-butyl), have been synthesized and their fluorescent responses toward zinc ion were investigated. These compounds exhibit zinc ion-induced fluorescence and their intensities decrease as the alkyl groups become larger. The t-butyl derivative (BQDtBEN) exhibited negligible fluorescence even in the presence of zinc ion. The fluorescence intensity of the zinc complex of the bisquinoline derivative (BQDMEN) is higher than that of TQEN (N,N,N′,N′-tetrakis(2-quinolylmethyl)ethylenediamine), indicating that the TQEN-Zn complex has an intramolecular quenching mechanism due to the energy transfer among four quinoline rings and the remaining photoinduced electron transfer (PET) mechanism. Introduction of methoxy substituents into the quinoline ring shifted the excitation and emission wavelengths towards a lower-energy direction and increased the fluorescence intensity, which allows N,N′-bis(6-methoxy-2-quinolylmethyl)-N,N′-dimethylethylenediamine (6-MeOBQDMEN) to be used for cellular fluorescent microscopic analysis (λ_ex = 331 nm, λ_em = 406 nm and ϕ = 0.28 for 6-MeOBQDMEN-Zn complex)

Two cyclohexanediamine-based tetrakisquinoline derivatives, N,N,N′,N′-tetrakis(2-quinolylmethyl)-trans-1,2-cyclohexanediamine (TQDACH) and N,N,N′,N′-tetrakis(1-isoquinolylmethyl)-trans-1,2-cyclohexanediamine (1-isoTQDACH), have been prepared and their zinc-induced fluorescent response was investigated. In DMF–H₂O (1 : 1) solution, TQDACH exhibits increase of fluorescence at 455 nm in the presence of 1 eq. of zinc ion (λ_ex = 317 nm, ϕ = 0.010). Similarly, 1-isoTQDACH exhibited fluorescence enhancement upon binding with zinc (λ_ex = 325 nm, λ_em = 352 and 475 nm, ϕ = 0.032). The fluorescence intensity ratio induced by cadmium relative to zinc (I_Cd/I_Zn) for these 1,2-cyclohexanediamine probes is lower than those for the corresponding ethylenediamine derivatives, TQEN and 1-isoTQEN. Crystal structures of the zinc and cadmium complexes of TQDACH and 1-isoTQDACH reveal the superior metal binding ability of the 1,2-cyclohexanediamine and isoquinoline moieties in comparison to ethylenediamine and quinoline. The conformational restriction afforded by the 1,2-cyclohexanediamine skeleton upon zinc binding leads to enhanced fluorescence intensity and strong metal binding affinity.