Molecular two-point recognition of fructosyl valine and fructosyl glycyl histidine in water by fluorescent Zn(II)-terpyridine complexes bearing boronic acids.

Selective recognition of fructosyl amino acids in water by arylboronic acid-based receptors is a central field of modern supramolecular chemistry that impacts biological and medicinal chemistry. Fructosyl valine (FV) and fructosyl glycyl histidine (FGH) occur as N-terminal moieties of human glycated hemoglobin; therefore, the molecular design of biomimetic receptors is an attractive, but very challenging goal. Herein, we report three novel cationic Zn-terpyridine complexes bearing a fluorescent N-quinolinium nucleus covalently linked to three different isomers of strongly acidified phenylboronic acids (ortho-, 2Zn; meta-, 3Zn and para-, 4Zn) for the optical recognition of FV, FGH and comparative analytes (D-fructose, Gly, Val and His) in pure water at physiological pH. The complexes were designed to act as fluorescent receptors using a cooperative action of boric acid and a metal chelate. Complex 3Zn was found to display the most acidic -B(OH)2 group (pKa = 6.98) and exceptionally tight affinity for FV (K = 1.43 × 105 M-1) with a strong quenching analytical response in the micromolar concentration range. The addition of fructose and the other amino acids only induced moderate optical changes. On the basis of several spectroscopic tools (1H, 11B NMR, UV-Vis, and fluorescence titrations), ESI mass spectrometry, X-ray crystal structure, and DFT calculations, the interaction mode between 3Zn and FV is proposed in a 1 : 1 model through a cooperative two-point recognition involving a sp3 boronate-diol esterification with simultaneous coordination bonding of the carboxylate group of Val to the Zn atom. Fluorescence quenching is attributed to a static complexation photoinduced electron transfer mechanism as evidenced by lifetime experiments. The addition of FGH to 3Zn notably enhanced its emission intensity with micromolar affinity, but with a lower apparent binding constant than that observed for FV. FGH interacts with 3Zn through boronate-diol complexation and coordination of the imidazole ring of His. DFT-optimized structures of complexes 3Zn-FV and 3Zn-FGH show a picture of binding which shows that the Zn-complex has a suitable (B⋯Zn) distance to the two-point recognition with these analytes. Molecular recognition of fructosyl amino acids by transition-metal-based receptors has not been explored until now.

Selective Luminescent Chemosensing of Chloride Based on a Cyclometalated Platinum(II) Complex in Water: Crystal Structures, Spectroscopic Studies, Extraction, and Bioimaging.

Selective anion sensing by luminescent chemosensors capable of operating in aqueous conditions is a central field of modern supramolecular chemistry that impacts analytical and biological chemistry. A cationic cyclometalated [Pt(N^C^N)NCCH3]OTf complex, 1 [N^C^N = 1,3-bis(1-(p-tolyl)-benzimidazol-2'-yl)benzene, OTf = triflate], was prepared, structurally described by single-crystal X-ray diffraction and studied in-depth as a luminescent chemosensor for anions in aqueous phase and solid state. A series of related neutral [Pt(N^C^N)X] complexes (X = Cl, 2; CN, 3 and I, 4) were formed readily upon treatment of 1 with the respective NaX salt in aqueous media and were described structurally by X-ray diffraction. Complex 1 is hydrostable with phosphorescent green emission originated by intraligand transitions, and [dyz(Pt) → π*(N^C^N)] charge transfer transitions, as evidenced by TD-DFT calculations and lifetime. Additions of halides, pseudohalides, oxyanions, and dicarboxylates to a neutral aqueous solution of 1 modified its green emission intensity with a pronounced affinity (K = 1.5 × 105 M-1) and turn-on signal toward Cl- within the micromolar concentration range. Pt complex 1 is two orders of magnitude more selective for Cl- than the other halides, CN- and basic oxyanions. Such Cl- affinity for a metal-based chemosensor in aqueous media is still rare. On the basis of X-ray crystallographic analysis and multiple spectroscopic tools (NMR, UV-vis, luminescence, MS, lifetimes) the origin of this selectivity hinges on the cooperative three-point recognition involving one coordination bond (Pt-Cl) and two convergent short C-H···Cl- contacts. This strong affinity and efficient optical response can be utilized in quantitative Cl- sensing in real samples and solid-liquid extractions. Additionally, chloro-Pt complex, 2 may be relevant to bioimaging as a marker for cell nuclei, as revealed by its emission within living cells and intracellular distribution by confocal microscopic studies. These results demonstrate the usefulness of the new water-stable luminescent Pt-N^C^N complexes as effective analytical tools in anion sensing and extraction agents.

Facile, Single-Step Synthesis of a Series of D-Ring Ethisterones Substituted with 1,4-1,2,3-Triazoles: Preliminary Evaluation of Cytotoxic Activities.

A series of new D-ring ethisterones substituted with 1,4-1,2,3-triazoles were obtained in a facile manner via click chemistry reactions. The new compounds were characterized by multinuclear NMR spectroscopy, mass spectrometry, IR and unequivocally by single crystal X-ray diffraction studies for compound 1. The cytotoxic activity of these derivatives was tested against a series of human cancer cell lines including human glioblastoma (U-251), human prostatic adenocarcinoma (PC-3), human colorectal adenocarcinoma (HCT-15), human mammary adenocarcinoma (MCF-7), human chronic myelogenous leukemia (K562), and human lung adenocarcinoma (SKLU-1). Derivatives (3, X=Cl) and (5, X=I) showed promising cytotoxicity activities for leukemia adenocarcinoma (K562) and lung adenocarcinoma (SKLU). CI50% of K562: 11.72±0.9 µM (3) and 24.50±1.0 µM (5). CI50% of SKLU: 14.9±0.8 µM (3) and 46.0±2.8 µM (5). In addition, DNA docking simulations showed that all compounds interact with DNA through crosslink instrastrand p-alkyl-like interactions.

Efficient fluorescent recognition of ATP/GTP by a water-soluble bisquinolinium pyridine-2,6-dicarboxamide compound. Crystal structures, spectroscopic studies and interaction mode with DNA.

The new dicationic pyridine-2,6-dicarboxamide-based compound 1 bearing two N-alkylquinolinium units was synthesized, structurally determined by single-crystal X-ray diffraction, and studied in-depth as a fluorescent receptor for nucleotides and inorganic phosphorylated anions in pure water. The addition of nucleotides to 1 at pH = 7.0 quenches its blue emission with a selective affinity towards adenosine 5'-triphosphate (ATP) and guanosine 5'-tripohosphate (GTP) over other nucleotides such CTP, UTP, ADP, AMP, dicarboxylates and inorganic anions. On the basis of the spectroscopic tools (1H, 31P NMR, UV-vis, fluorescence), MS measurements and DFT calculations, receptor 1 binds ATP with high affinity (log K = 5.04) through the simultaneous formation of strong hydrogen bonds and π-π interactions between the adenosine fragment and quinolinium ring with binding energy calculated in 8.7 kcal mol-1. High affinity for ATP/GTP is attributed to the high acidity of amides and preorganized rigid structure of 1. Receptor 1 is an order of magnitude more selective for ATP than GTP. An efficient photoinduced electron transfer quenching mechanism with simultaneous receptor-ATP complexation in both the excited and ground states is proposed. Additionally, multiple spectroscopic studies and molecular dynamics simulations showed that 1 can intercalate into DNA base pairs.

Chemosensing of neurotransmitters with selectivity and naked eye detection of l-DOPA based on fluorescent Zn(ii)-terpyridine bearing boronic acid complexes.

Biological catecholamines such as l-DOPA and dopamine play vital physiological roles in the brain and are chemical indicators of human diseases. A new range of fluorescent Zn(ii)-terpyridine complexes are described and studied in-depth as chemosensors for catecholamine-based neurotransmitters and nucleosides in pure water. The new Zn-terpyridine-based chemosensors contain a cationic N-isoquinolinium nucleus as the optical indicator covalently linked to three different isomers of strongly acidified phenylboronic acids (ortho-, 2.Zn; meta-, 3.Zn and para-, 4.Zn, substituted derivatives) as catechol binding sites. The addition of l-DOPA, dopamine, epinephrine, l-tyrosine and nucleosides to Zn(ii)-boronic acid chemosensors at physiological pH quenches their blue emission with a pronounced selectivity and an unprecedented high affinity towards l-DOPA (log K = 6.01). This efficient response by l-DOPA was also observed in the presence of coexisting species in blood plasma and urine with a detection limit of 3.0 µmol L-1. A photoinduced electron transfer quenching mechanism with simultaneous chemosensor-l-DOPA complexation in both the excited and ground states is proposed. The fluorescence experimental observations show that the 2.Zn·eosin-Y adduct can be used as a selective naked-eye chemosensing ensemble for l-DOPA with a fast turn-on fluorescent response and color change from blue to green under UV light at the micromolar level. On the basis of multiple spectroscopic techniques (1H, 11B NMR, UV-Vis, and fluorescence), MS-ESI experiments, crystal structures, and DFT calculations, the binding mode between Zn(ii)-chemosensors and l-DOPA is proposed in a 1 : 1 model through a cooperative two-point recognition involving the reversible esterification of the boronic acid moiety with the aromatic diol fragment of l-DOPA together with the coordination of the carboxylate anion to the Zn(ii) atom with strong electrostatic contribution.

Regioselective hypervalent iodine-induced Favorskii rearrangement of 3-oxo-5ß-steroids.

Treatment of 3-oxo-5ß-steroids with diacetoxyiodobenzene/KOH triggered a fast and regioselective Favorskii rearrangement that exclusively led to 3ß-methoxycarbonyl-5ß-4-norsteroids in good yields. The outcome of the reaction indicates that although both Cyclopropanone and Semi-benzylic pathways are possible, in the case of 3-oxo-5ß-steroids, only the last participates. Unambiguous characterization of the products was achieved by NMR and X-ray Diffraction studies.