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 (<i>N,N,N</i>′<i>,N</i>′-tetrakis­(6-methoxy-8-quinolylmethyl)-2-hydroxy-1,3-propanediamine) exhibited Zn²⁺-induced fluorescence enhancement with high specificity and sensitivity (<i>I</i>_Zn/<i>I</i>₀ = 57 and <i>I</i>_Cd/<i>I</i>_Zn = 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 (PO₄^3–) 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

Zinc-Specific Fluorescent Response of Tris(isoquinolylmethyl)amines (isoTQAs)

Isoquinoline-based tetradentate ligands with <i>C</i>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/H₂O (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 (<i>N,N,N′,N′</i>-tetrakis­(isoquinolylmethyl)­ethylenediamines) leads to a higher fluorescent response toward zinc relative to cadmium

Zinc-Specific Fluorescent Response of Tris(isoquinolylmethyl)amines (isoTQAs)

Isoquinoline-based tetradentate ligands with <i>C</i>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/H₂O (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 (<i>N,N,N′,N′</i>-tetrakis­(isoquinolylmethyl)­ethylenediamines) leads to a higher fluorescent response toward zinc relative to cadmium

Quantitative Fluorescent Detection of Pyrophosphate with Quinoline-Ligated Dinuclear Zinc Complexes

Dinuclear zinc complex [Zn₂(TQHPN)­(AcO)]²⁺ exhibits characteristic fluorescence response (λ_ex = 317 nm and λ_em = 455 nm) toward pyrophosphate (PPi) with maximum fluorescence upon 1:1 Zn₂(TQHPN)–PPi complex formation. The crystallographic investigation utilizing P¹P²–Ph₂PPi revealed that the fluorescent response mechanism is due to intramolecular excimer formation of two quinoline rings

Quantitative Fluorescent Detection of Pyrophosphate with Quinoline-Ligated Dinuclear Zinc Complexes

Dinuclear zinc complex [Zn₂(TQHPN)­(AcO)]²⁺ exhibits characteristic fluorescence response (λ_ex = 317 nm and λ_em = 455 nm) toward pyrophosphate (PPi) with maximum fluorescence upon 1:1 Zn₂(TQHPN)–PPi complex formation. The crystallographic investigation utilizing P¹P²–Ph₂PPi revealed that the fluorescent response mechanism is due to intramolecular excimer formation of two quinoline rings

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

Dinuclear Zn²⁺ complexes with HTQHPN (<i>N,N,N</i>′<i>,N</i>′-tetrakis­(2-quinolylmethyl)-2-hydroxy-1,3-propanediamine) derivatives have been prepared, and their pyrophosphate (PPi, P₂O₇^4–) 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 (<i>N,N,N</i>′<i>,N</i>′-tetrakis­(6-fluoro-2-quinolylmethyl)-2-hydroxy-1,3-propanediamine), and HT­(8Q)­HPN (<i>N,N,N</i>′<i>,N</i>′-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 (<i>I</i>_PPi/<i>I</i>₀ = 12.5) and selectivity toward PPi sensing (<i>I</i>_ATP/<i>I</i>_PPi = 20% and <i>I</i>_ADP/<i>I</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

Cd²⁺-Specific Fluorescence Response of Methoxy-Substituted <i>N</i>,<i>N</i>‑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

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 <i>trans</i>-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 <i>para</i> 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 <i>ortho</i> and <i>para</i> positions in the presence of EDCI/HOBt/Et₃N at room temperature or at 60–80 °C gave tetrahydrobenz­[<i>f</i>]­isoindolines via [4 + 2] cycloaddition as major products. DFT studies have been performed to explained the observed [2 + 2]/[4 + 2] selectivity