Efficient Synthesis and Structural Analysis of Chiral 4,4'-Biazulene.

4,4'-Biazulene is a potentially attractive key component of an axially chiral biaryl compound, however, its structure and properties have not been clarified owing to the lack of its efficient synthesis. We report a breakthrough in the reliable synthesis of 4,4'-biazulene, which is achieved by the access to azulen-4-ylboronic acid pinacol ester and 4-iodoazulene as novel key synthetic intermediates for the Suzuki-Miyaura cross-coupling reaction. The X-ray crystallographic analysis of 4,4'-biazulene confirmed its axial chirality. The enantiomers of 4,4'-biazulene were successfully resolved by HPLC on the chiral stationary phase column. The kinetic experiments and DFT calculations indicate that the racemization energy barrier of 4,4'-biazulene is comparable to that of 1,1'-binaphthyl.

Color Change of Indole Squaraine between Blue and Yellow with Golden Luster.

Color change of materials by external stimulus has attracted much attention for various applications. We synthesized 1,3-bis(3,3-dimethyl-2-methylene indolenine)squaraine (ISQ), which was a yellow powder with golden luster (ISQ(gold)) and whose color changed to blue (ISQ(blue)) by being ground using mortar and pestle. Scanning electron microscopy indicated that ISQ(gold) consisted of laminated plate-like crystals with a large flat surface, which was attributable to (2 0-2) facets of monoclinic crystals. Measurements of the diffuse reflectance spectra revealed that J- and H-type aggregates of ISQ were formed by increasing the weight percent of ISQ(blue) in the mixture with BaSO4. A thin film, which was prepared by a spin-coating of ethanol with dissolved ISQ(blue) on glass substrates, looked blue on a white paper, whereas it looked yellowish on a black paper. By repeating the coating process, the film thickness increased, and the thick film exhibited yellow with golden luster regardless of the background color. These results indicate that the color depends on whether the transmitted light through ISQ or the reflected light on the ISQ surface mainly contributes to color vision. To neglect the effect of the transmitted light and intensify the reflection on the surface, a pellet with a smooth surface was prepared by pressing ISQ(gold) or ISQ(blue) at 20 kg/cm2. The ISQ(blue) pellet consisted of the laminated sheets and was dark blue-green. However, under light irradiation, the ISQ(blue) pellet exhibited a yellow color with golden luster, whose specular reflection spectrum was similar to that of the ISQ(gold) pellet. Our results indicate that the color of ISQ is tunable by controlling the transmission and the reflection of the light, including the specular and diffuse reflections.

Cd2+-Specific Fluorescence Response of Methoxy-Substituted N,N-Bis(2-quinolylmethyl)-2-methoxyaniline Derivatives.

The N3O1 tetradentate ligand, TriMeOBQMOA (N,N-bis(5,6,7-trimethoxy-2-quinolylmethyl)-2-methoxyaniline), was developed as a Cd2+-specific fluorescent sensor. The structure of TriMeOBQMOA is half of TriMeOBAPTQ (N,N,N',N'-tetrakis(5,6,7-trimethoxy-2-quinolylmethyl)-1,2-bis(2-aminophenoxy)ethane), which is a tetrakisquinoline derivative of the well-known calcium chelator BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid). The fluorescent Cd2+ selectivity of TriMeOBAPTQ (IZn/ICd = 5.3% in the presence of 3 equiv of metal ions in MeOH-HEPES buffer (9:1)) comes from the formation of fluorescent dinuclear cadmium (M2L) and nonfluorescent OH-bridged dizinc ((µ-OH)M2L) complexes. TriMeOBQMOA also exhibits excellent Cd2+ specificity in fluorescence enhancement (IZn/ICd = 2.3% in the presence of 5 equiv of metal ions in DMF-HEPES buffer (1:1, HEPES 50 mM, KCl 0.1 M, pH = 7.5)) via substantial formation of a highly fluorescent bis(µ-chloro)dinuclear cadmium complex ([Cd2(µ-Cl)2L2]2+), which is in equilibrium with the mononuclear Cd2+ complex ([CdLCl]+), and extremely poor stability of the TriMeOBQMOA-Zn2+ complex. The all-nitrogen derivatives of BQMOA and BAPTQ, namely, N,N-BQDMPHEN (N,N-bis(2-quinolylmethyl)-N',N'-dimethyl-1,2-phenylenediamine) and BPDTQ (N,N,N',N'-tetrakis(2-quinolylmethyl)-2,2'-(N,N'-dimethylethylenediamino)dianiline), respectively, and their methoxy-substituted derivatives were also prepared, and the fluorescent metal ion sensing properties are discussed.

Cd2+-Selective Fluorescence Enhancement of Bisquinoline Derivatives with 2-Aminoethanol Skeleton.

The development of fluorescent Cd2+ sensors requires strict selectivity over Zn2+ because of the high availability of Zn2+ in the natural environment. In this paper, bisquinoline-based fluorescent sensors with a 2-aminoethanol backbone were investigated. The weak coordination ability of quinoline compared to well-studied pyridine is suitable for Cd2+ selectivity rather than Zn2+. In the presence of 3 equiv. of metal ions, TriMeO-N,O-BQMAE (N,O-bis(5,6,7-trimethoxy-2-quinolylmethyl)-2-methylaminoethanol (3)), as well as its N,N-isomer TriMeO-N,N-BQMAE (N,N-bis(5,6,7-trimethoxy-2-quinolylmethyl)-2-methoxyethylamine (6)), exhibits Cd2+-selective fluorescence enhancement over Zn2+ in DMF-HEPES buffer (1:1, 50 mM HEPES, 0.1 M KCl, pH = 7.5) (IZn/ICd = 26-34%), which has similar selectivity in comparison to the corresponding ethylenediamine derivative TriMeOBQDMEN (N,N'-bis(5,6,7-trimethoxy-2-quinolylmethyl)-N,N'-dimethylethylenediamine) under the same experimental condition (IZn/ICd = 24%). The fluorescence mechanisms of N,O- and N,N-isomers of BQMAE are quite different, judging from the fluorescence lifetimes of their metal complexes. The Cd2+ complex with TriMeO-N,O-BQMAE (3) exhibits a long fluorescence lifetime similar to that of TriMeOBQDMEN via intramolecular excimer emission, whereas the Cd2+ complex with TriMeO-N,N-BQMAE (6) exhibits a short lifetime from monomer emission.

Intramolecular Diels-Alder Reactions of α-Bromostyrene-Functionalized Unsaturated Carboxamides.

Intramolecular cycloaddition reactions of α-bromostyrene-functionalized amides of monomethyl fumarate were investigated. The reaction of the amides with Et3N in toluene at 110 °C gave 1,4-dihydronaphthalenes. The 1,4-dihydronaphthalenes may be produced via the intramolecular Diels-Alder reaction, proton transfer, and dehydrobromination by a base, along with C═C bond isomerization by proton transfer. The reaction of amide derivatives with halogen on a benzene ring and alkali metal carbonates in toluene at 110 °C gave naphthalene derivatives directly. Dehydrogenation of various 1,4-dihydronaphthalenes with cesium or rubidium carbonate in toluene at 110 °C gave naphthalene derivatives. The retardation by TEMPO, acceleration by air for some substrates, and density functional theory calculations suggest a radical mechanism caused by intervention of molecular oxygen.

A Synthetic Model for the Possible FeIV2(µ-O)2 Core of Methane Monooxygenase Intermediate Q Derived from a Structurally Characterized FeIIIFeIV(µ-O)2 Complex.

A bis(µ-oxo)diiron(IV,IV) complex as a model for intermediate Q in the methane monooxygenase reaction cycle has been prepared. The precursor complex with a [FeIIIFeIV(µ-O)2] core was fully characterized by X-ray crystallography and other spectroscopic analyses and was converted to the [FeIV2(µ-O)2] complex via electrochemical oxidation at 1000 mV (vs Ag/Ag+) in acetone at 193 K. The UV-vis spectral features, Mössbauer parameters (ΔEQ = 2.079 mm/s and δ = -0.027 mm/s), and EXAFS analysis (Fe-O/N = 1.73/1.96 Å and Fe···Fe = 2.76 Å) support the structure of the low-spin (S = 1, for each Fe) [FeIV2(µ-O)2] core. The rate constants of the hydrogen abstraction reaction from 9,10-dihydroanthracene at 243 K suggest the high reactivity of these synthetic bis(µ-oxo)diiron complexes supported by simple N4 tripodal ligand.

Switching of Fluorescent Zn/Cd Selectivity in N,N,N',N'-Tetrakis(6-methoxy-2-quinolylmethyl)-1,2-diphenylethylenediamine by One Asymmetric Carbon Atom Inversion.

A quinoline-based hexadentate ligand, (S,S)-N,N,N',N'-tetrakis(6-methoxy-2-quinolylmethyl)-1,2-diphenylethylenediamine ((S,S)-6-MeOTQPh2EN), exhibits fluorescence enhancement at 498 nm upon addition of 1 equiv of Zn2+ (IZn/I0 = 12, φZn = 0.047) in aqueous DMF solution (DMF/H2O = 2:1). Addition of 1 equiv of Cd2+ affords a much smaller fluorescence increase at the same wavelength (ICd/I0 = 2.5, ICd/IZn = 21%). The trivalent metal ions such as Al3+, Cr3+, and Fe3+ also exhibit fluorescence enhancement at 395 nm (IAl/I0 = 22, ICr/I0 = 6 and IFe3+/I0 = 13). In contrast, meso-6-MeOTQPh2EN exhibits a Cd2+-selective fluorescence increase at 405 nm in the presence of 1 equiv of metal ion (ICd/I0 = 11.5, φCd = 0.022), while Zn2+ induces a smaller fluorescent response under the same experimental conditions (IZn/I0 = 3.3, IZn/ICd = 29%). In this case, the fluorescence intensities of meso-6-MeOTQPh2EN in the presence of a large amount of Zn2+ and Cd2+ become similar. This diastereomer-dependent, fluorescent metal ion specificity is derived from the Zn2+-specific intramolecular excimer formation in (S,S)-6-MeOTQPh2EN-Zn2+ complex and higher binding affinity of meso-6-MeOTQPh2EN with Cd2+ in comparison to Zn2+. The more conformationally restricted diastereomeric pair, namely, cis- and trans-TQDACHs (cis- and trans-N,N,N',N'-tetrakis(2-quinolylmethyl)-1,2-diaminocyclohexanes), both exhibit Zn2+-specific fluorescence enhancement because of the high metal binding affinity and intramolecular excimer forming property derived from the rigid DACH backbone.

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.

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).

Intramolecular [2 + 2] and [4 + 2] Cycloaddition Reactions of Cinnamylamides of Ethenetricarboxylate in Sequential Processes.

Intramolecular [2 + 2] and [4 + 2] cycloaddition reactions of cinnamylamides of ethenetricarboxylate in sequential processes have been studied. Reaction of 1,1-diethyl 2-hydrogen ethenetricarboxylate and trans-cinnamylamines in the presence of EDCI/HOBt/Et3N led to pyrrolidine products in one pot, via intramolecular [2 + 2], [4 + 2], and some other cyclizations. The types of the products depend on the substituents on the benzene ring and the reaction conditions. Reaction of cinnamylamines without substituents on the benzene ring and with halogens and OMe on the para position at room temperature gave cyclobutane-fused pyrrolidines as major products via [2 + 2] cycloaddition. The reaction at 80 °C in 1,2-dichloroethane gave δ-lactone fused pyrrolidines as major products, probably via ring-opening of the cyclobutanes. Interestingly, reaction of 1,1-diethyl 2-hydrogen ethenetricarboxylate and cinnamylamines bearing electron-withdrawing groups such as NO2, CN, CO2Me, CO2Et, and CF3 on ortho and para positions in the presence of EDCI/HOBt/Et3N at room temperature or at 60-80 °C gave tetrahydrobenz[f]isoindolines via [4 + 2] cycloaddition as major products. DFT studies have been performed to explained the observed [2 + 2]/[4 + 2] selectivity.

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.

Characteristic conformation of Mosher's amide elucidated using the cambridge structural database.

Conformations of the crystalline 3,3,3-trifluoro-2-methoxy-2-phenylpropanamide derivatives (MTPA amides) deposited in the Cambridge Structural Database (CSD) were examined statistically as Racid-enantiomers. The majority of dihedral angles (48/58, ca. 83%) of the amide carbonyl groups and the trifluoromethyl groups ranged from -30° to 0° with an average angle θ1 of -13°. The other conformational properties were also clarified: (1) one of the fluorine atoms was antiperiplanar (ap) to the amide carbonyl group, forming a staggered conformation; (2) the MTPA amides prepared from primary amines showed a Z form in amide moieties; (3) in the case of the MTPA amide prepared from a primary amine possessing secondary alkyl groups (i.e., Mosher-type MTPA amide), the dihedral angles between the methine groups and the carbonyl groups were syn and indicative of a moderate conformational flexibility; (4) the phenyl plane was inclined from the O-Cchiral bond of the methoxy moiety with an average dihedral angle θ2 of +21°; (5) the methyl group of the methoxy moiety was ap to the ipso-carbon atom of the phenyl group.

Structural and electrochemical properties of mononuclear copper(II) complexes with pentadentate ethylenediamine-based ligands with pyridine/quinoline/isoquinoline/quinoxaline binding sites.

N-Monosubstituted ethylenediamine derivatives with three methylene-tethered aromatic groups ((ArCH2)2NCH2CH2N(R)CH2Ar (R-ArArAr), where Ar = 2-pyridyl, 2-quinolyl, 1- and 3-isoquinolyl and 2-quinoxalyl; R = methyl, benzyl and phenyl) were utilized as pentadentate ligands for copper(II) complexation. Fifteen mononuclear copper(II) complexes were synthesized and exhibit differences in cyclic voltammetry, absorption spectroscopy and solid state geometries, depending on the aromatic group (Ar) and the substituent on the aliphatic nitrogen atom (R) of the ligand. Compared with the pyridine and isoquinoline complexes, the quinoline and quinoxaline derivatives exhibit distinct Cu(II)/Cu(I) redox potentials and d-d transition absorption wavelengths. Similarly, the phenyl derivatives are different from their methyl and benzyl counterparts. These characteristic trends are discussed in relation to the square-pyramidal/trigonal-bipyramidal structure of the complexes which is perturbed by the location of quinoline moieties in the penta- or hexacoordinate complexes with Jahn-Teller distortion. In addition, the results are compared to the copper(II) complexes with pyridine/quinoline mixed ligands, Ph-Ar1Ar2Ar3 ((Ar1CH2)(Ar2CH2)NCH2CH2N(Ph)CH2Ar3).

Synthesis, characterization, and biological studies of emissive rhenium-glutamine conjugates.

Two new rhenium complexes containing pyridine-triazole (pyta) and quinoline-triazole (quinta) ligands with attached glutamine-targeting agents have been characterized and tested for uptake in the HT-29 human colon adenocarcinoma cell line. The glutamine moiety in Re(CO)3Br(pyta) (1) and Re(CO)3Br(quinta) (2) remains pendant in solution. Both complexes exhibit absorptions in the 300-400-nm range with metal-to-ligand charge transfer (MLCT) character, as predicted by time-dependent density functional theory calculations. Geometrical analysis by theoretical calculations provides information on the cationic complexes 1 (+) and 2 (+) resulting from aquo for halide ligand exchange under aqueous conditions. The emissive properties of both complexes were studied under aqueous conditions, and the measured quantum yields were 0.46 % for 1 (+) and 0.18 % for 2 (+). The large Stokes shifts and oxygen sensitivity of the emission suggest a (3)MLCT process for both complexes. Cell studies in the HT-29 cell line demonstrate that both complexes are nontoxic over a large concentration range (0-1.4 mM). Preliminary uptake studies show that 2 (+), but not 1 (+), displays significant concentration-dependent uptake at 3 and 24 h.

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.

Effect of methoxy substituents on fluorescent Zn2+/Cd2+ selectivity of bisquinoline derivatives with a N,N'-dimethylalkanediamine skeleton.

BQDMEN (N,N'-bis(2-quinolylmethyl)-N,N'-dimethylethylenediamine) and its 6-methoxyquinoline derivative (6-MeOBQDMEN) are fluorescent Zn2+ sensors with minor response to Cd2+ (IZn/ICd = 3.9 for BQDMEN and IZn/ICd = 2.2 for 6-MeOBQDMEN in the presence of 1 equiv. of metal ion). Nevertheless, the introduction of three methoxy substituents at the 5,6,7-position of both quinoline rings of BQDMEN reversed the fluorescent metal ion selectivity to favor Cd2+ (IZn/ICd = 0.22 for TriMeOBQDMEN in the presence of 1 equiv. of metal ion). This reversal of Zn2+/Cd2+ preference in fluorescence enhancement by trimethoxy substitution was also valid for 1,3-propanediamine derivatives. The X-ray crystallography, ESI-MS, fluorescence lifetime and pH profile of the fluorescence intensity suggest that the dinuclear cadmium complex is a key component of the fluorescent Cd2+ selectivity in TriMeOBQDMEN.

Evaluation of oxygen-containing pentadentate ligands with pyridine/quinoline/isoquinoline binding sites via the structural and electrochemical properties of mononuclear copper(II) complexes.

Eighteen mononuclear copper(II) complexes with oxygen-containing N4O1 pentadentate ligands were prepared. The ligand library consists of 2-aminoethanol derivatives ((Ar1CH2)(Ar2CH2)NCH2CH2OCH2Ar3) bearing three nitrogen-containing heteroaromatics (Ars) including pyridine, quinoline and isoquinoline via a methylene linker. Systematic replacements of pyridine binding sites with quinolines and isoquinolines reveal the general trends in the perturbation of bond distances and angles, the redox potential and the absorption maximum wavelength of the copper(II) complexes, depending on the position and number of (iso)quinoline heteroaromatics. The small effect on the redox potentials resulting from quinoline substitution at the Ar3 position (near oxygen) of the ligand comes from the steric hindrance of the peri hydrogen atom in the quinoline moiety at this position, which removes the counter anion to enhance the coordination of quinoline nitrogen and ether oxygen atoms to the metal centre. In the absorption spectra of copper(II) complexes in the d-d transition region, the quinoline substitution at this site (Ar3) exhibits an opposite effect to those at the Ar1 and Ar2 sites. The electronic and steric contributions of the heteroaromatic binding sites to the ligand properties are comprehensively discussed.

Photooxidative cleavage of zinc 20-substituted chlorophyll derivatives: conformationally P-helix-favored formation of regioselectively 19-20 opened linear tetrapyrroles.

Photoreaction of zinc methyl 20-substituted meso(pyro)pheophorbide-a prepared by modifying naturally occurring chlorophyll-a in the presence of oxygen molecules gave its C19-C20 oxidative cleavage (1-carbonyl-19-oxo-bilatrienes) as the major products and the regioisomeric C1-C20 cleavage (19-carbonyl-1-oxo-bilatrienes) as the minor products. The resulting zinc complexes of linear tetrapyrroles took a helical conformation and the P-conformers were preferential over the M-stereoisomers due to the presence of their 17S,18S-chiral centers. The helical conformers (diastereomers) of the corresponding nickel complexes were separated by reverse-phase or chiral HPLC and their conformational changes were observed in solution.

Zinc-specific fluorescent response of tris(isoquinolylmethyl)amines (isoTQAs).

Isoquinoline-based tetradentate ligands with C(3)-symmetry, tris(1- or 3-isoquinolylmethyl)amine (1- or 3-isoTQA), have been prepared and their zinc-induced fluorescence enhancement was investigated. Upon excitation at 324 nm, 1-isoTQA shows very weak fluorescence (ϕ = ∼0.003) in DMF/H(2)O (1/1) solution. In the presence of zinc ion, 1-isoTQA exhibits fluorescence increase (ϕ = 0.041) at 359 and 470 nm. This fluorescence enhancement at 470 nm is specific for zinc. However, 3-isoTQA exhibited a smaller fluorescence enhancement upon zinc complexation (ϕ = 0.017, λ(em) = 360 and 464 nm) compared with 1-isoTQA. Crystal structures of zinc complexes of isoTQAs demonstrate the diminished steric crowding and shorter Zn-N(aromatic) distances compared with isoTQENs (N,N,N',N'-tetrakis(isoquinolylmethyl)ethylenediamines) leads to a higher fluorescent response toward zinc relative to cadmium.

Quinoline-based, glucose-pendant fluorescent zinc probes.

Quinoline-based tetradentate ligands with glucose pendants, N,N'-bis[2-(ß-d-glucopyranosyloxy)ethyl]-N,N'-bis[(6-methoxyquinolin-2-yl)methyl]ethylenediamine (N,N'-6-MeOBQBGEN) and its N,N-counterpart, N,N-6-MeOBQBGEN, have been prepared, and their fluorescence-spectral changes upon Zn binding were investigated. Upon excitation at 336 nm, N,N'-6-MeOBQBGEN showed weak fluorescence (ϕ ≈ 0.016) in HEPES buffer (HEPES 50 mM, KCl 100 mM, pH 7.5). In the presence of Zn, N,N'-6-MeOBQBGEN exhibited a significant increase in fluorescence (ϕ = 0.096) at 414 nm. The fluorescence enhancement is specific for Zn and Cd (I(Cd) /I(Zn) of 50% at 414 nm). On the other hand, N,N-6-MeOBQBGEN exhibited a smaller fluorescence enhancement upon Zn complexation (ϕ = 0.043, λ(ex) = 334 nm, λ(em) = 407 nm) compared with N,N'-6-MeOBQBGEN. Fluorescence microscopic analysis using PC-12 rat adrenal cells revealed that N,N'-6-MeOBQBGEN exhibits a 1.8-fold higher fluorescence-signal response to Zn ion concentration compared with sugar-depleted compound 2 (N,N'-bis[(6-methoxyquinolin-2-yl)methyl]ethylenediamine), due to its enhanced uptake into cells due to the targeting ability of the attached carbohydrates.