TQOPEN (N,N,N',N'-Tetrakis(2-quinolylmethyl)-3-oxa-1,5-pentanediamine) Family as Heptadentate Fluorescent Cd2+ Sensors.

A quinoline-based heptadentate ligand, N,N,N',N'-tetrakis(2-quinolylmethyl)-3-oxa-1,5-pentanediamine (TQOPEN), exhibits a fluorescence increase (ICd/I0 = 25, ϕCd = 0.017) at 428 nm upon addition of 1 equiv of Cd2+. In contrast, 1 equiv of Zn2+ induces a negligible fluorescence change due to weak interaction (IZn/I0 = 2.5, IZn/ICd = 10%). In comparison with TQOPEN, the thia and aza derivatives TQSPEN and TQNPEN exhibit improved Cd2+/Zn2+ selectivity and higher Cd2+-binding affinity, respectively. The solid-state structures of mononuclear Cd2+ and hydroxide-bridged dinuclear Zn2+ complexes of TQOPEN were elucidated by X-ray crystallography. Although the crystal structure of the TQOPEN-Cd2+ complex exhibits a six-coordinate metal center, in which one quinoline weakly interacts with the Cd center (Cd···Nquinoline = 3.303(3) Å), a 1H NMR study at 233 K suggests that all quinolines interact with the Cd center to form a symmetrical seven-coordinate structure in solution. Theoretical calculations (TDDFT) support the flexible coordination environment around the Cd center, leading to intramolecular excimer formation with two quinoline moieties in the excited state. The importance of a heptadentate structure was further demonstrated by the lack of Cd2+ specificity with hexadentate ligands TriQOPEN (N,N,N'-tris(2-quinolylmethyl)-3-oxa-1,5-pentanediamine) and TQCPEN (N,N,N',N'-tetrakis(2-quinolylmethyl)-1,5-pentanediamine).

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+)).

TQPHEN (N,N,N',N'-tetrakis(2-quinolylmethyl)-1,2-phenylenediamine) derivatives as highly selective fluorescent probes for Cd2+.

TQPHEN (N,N,N',N'-tetrakis(2-quinolylmethyl)-1,2-phenylenediamine) and its methoxy-substituted derivatives, 6-MeOTQPHEN (N,N,N',N'-tetrakis(6-methoxy-2-quinolylmethyl)-1,2-phenylenediamine) and TriMeOTQPHEN (N,N,N',N'-tetrakis(5,6,7-trimethoxy-2-quinolylmethyl)-1,2-phenylenediamine), were examined as fluorescent Cd(2+) sensors. Although the TQPHEN exhibits a negligible fluorescence response toward Zn(2+) due to weak binding affinity in DMF-H2O (1:1), a 6-fold fluorescence enhancement at 392 nm was observed in the presence of 1 equiv. of Cd(2+). Comprehensive X-ray crystallographic analyses of TQPHEN-Zn(2+) and TQPHEN-Cd(2+) complexes reveal that significant distortion in the Zn(2+) complex plays a key role in the Cd(2+) specificity of TQPHEN. The TriMeOTQPHEN exhibits excellent sensitivity and selectivity for Cd(2+) detection (ICd/I0 = 44, ICd/IZn = 20 and LODCd = ∼10 nM (LOD = limit of detection)). On the other hand, the trans-1,2-cyclohexanediamine derivative TQDACH (N,N,N',N'-tetrakis(2-quinolylmethyl)-trans-1,2-cyclohexanediamine) exhibits high Zn(2+) specificity in the fluorescence response and extremely high Zn(2+) binding affinity (Dalton Trans., 2013, 42, 9688). Subtle differences in the PHEN and DACH backbone significantly alter the stability with a specific metal and the fluorescence response of tetrakisquinoline-based fluorescent probes.

Quinoline-attached triazacyclononane (TACN) derivatives as fluorescent zinc sensors.

TACN (1,4,7-triazacyclononane) derivatives with three 6-methoxy-2-quinolylmethyl or 1-isoquinolylmethyl moieties were examined as fluorescent zinc sensors. Upon the addition of zinc, 6-MeOTQTACN (5) exhibited a 9-fold fluorescence increase at 420 nm (λex = 341 nm, ϕZn = 0.070). Fluorescence enhancement is specific for zinc and cadmium, although cadmium induces smaller increases (ICd/I0 = 3.6 and ICd/IZn = 40%). The isoquinoline analog 1-isoTQTACN (6) exhibits minimal fluorescence enhancement upon zinc binding. TPEN (N,N,N',N'-tetrakis(2-pyridylmethyl)ethylene-diamine) does not extract zinc from the 6-MeOTQTACN-Zn complex (5-Zn). The quantum yield, metal ion selectivity and metal binding affinity differences between TACN and ethylenediamine (EN) skeletons in quinoline-based ligands are discussed based on the X-ray crystallographic analysis of zinc and cadmium complexes, demonstrating the superiority of quinoline-TACN conjugates.