Cyano Derivatives of 7-Aminoquinoline That Are Highly Emissive in Water: Potential for Sensing Applications.

6-Cyano-7-aminoquinoline (6CN-7AQ) and 3-cyano-7-aminoquinoline (3CN-7AQ) were synthesized and found to exhibit intense emission with quantum yield as high as 63 % and 85 %, respectively, in water. Conversely, their derivatives 6-cyano-7-azidoquinoline (6CN-7N3 Q) and 3-cyano-7-azidoquinoline (3CN-7N3 Q) show virtually no emission, which makes them suitable to be used as recognition agents in azide reactions based on fluorescence recovery. Moreover, conjugation of 6CN-7AQ with a hydrophobic biomembrane-penetration peptide PFVYLI renders a nearly non-emissive 6CN-7AQ-PFVYLI composite, which can be digested by proteinase K, recovering the highly emissive 6CN-7AQ with ∼200-fold enhancement. The result provides an effective early confirmation for RT-qPCR in viral detection.

Catalytic-Type Excited-State N-H Proton-Transfer Reaction in 7-Aminoquinoline and Its Derivatives.

7-Aminoquinoline (7AQ) and various amino derivatives thereof (-NHR) have been strategically designed and synthesized to study their excited-state proton-transfer (ESPT) properties. Due to the large separation between the proton donor -NHR and the acceptor -N- site, ESPT in 7AQ derivatives, if available, should proceed under protic solvent catalysis. ESPT is found to be influenced by the acidity of -NHR and the basicity of the proton-acceptor -N- in the quinoline moiety. The latter is varied by the resonance effect at the quinoline -N- site induced by the -NHR substituent. For those 7AQ derivatives undergoing ESPT, increased quinoline basicity results in a faster rate of ESPT, implying that proton donation from methanol to the quinoline moiety may serve as a key step in the process. Our studies also indicate the existence of an equilibrium between cis and trans arrangements of -NHR in terms of its hydrogen-bond (H-bond) configuration with methanol, whereby only the cis-H-bonded form undergoes methanol-assisted ESPT. With one exception, the interconversion between cis and trans configurations is much faster than the rate of ESPT, yielding amino-type (normal form) and imine-type (proton-transfer tautomer) emissions with distinct relaxation dynamics.

The Quest of Excited-State Intramolecular Proton Transfer via Eight-Membered Ring π-Conjugated Hydrogen Bonding System.

Searching for eight-membered ring π-conjugated hydrogen bonding (8-MR H-bonding) systems with excited-state intramolecular proton transfer (ESIPT) property is seminal and synthetically challenging. In this work, a series of π-conjugated molecules (8-HB-1, 8-HB-L1 and 8-HB-2) potentially possessing 8-MR H-bonding are strategically designed, synthesized and characterized. The configurations of these three potential molecules are checked by their X-ray structures, among which 8-HB-L1 (a structurally locked 8-HB-1 core chromophore) is proved to be an 8-MR H-bonding system, whereas 8-HB-1 and 8-HB-2 are too sterically hindered to form the 8-MR intramolecular H-bond. The ESIPT property of 8-HB-L1 is confirmed by the dual fluorescence consisting of normal and proton-transfer tautomer emissions. The insight into the ESIPT process of 8-HB-L1 is provided by femtosecond fluorescence upconversion measurements together with computational simulation. The results demonstrate for the first time a successful synthetic route to attain the 8-MR H-bonding molecule 8-HB-L1 with ESIPT property.

Insight into the Amino-Type Excited-State Intramolecular Proton Transfer Cycle Using N-Tosyl Derivatives of 2-(2'-Aminophenyl)benzothiazole.

Studies have been carried out to gain insight in to an overall excited-state proton transfer cycle for a series of N-tosyl derivatives of 2-(2'-aminophenyl)benzothiazole. The results indicate that followed by ultrafast (<150 fs) excited-state intramolecular proton transfer (ESIPT), the titled compounds undergo rotational isomerization along the C1-C1' bond. For the model compound 2-(2'-tosylaminophenyl)benzothiazole (PBT-NHTs) the subsequent cis-trans isomerization process in both triplet and ground states are probed by nanosecond transient absorption (TA) and two-step laser-induced fluorescence (TSLIF) spectroscopy. Both TA and TSLIF results indicate the existence of a long-lived trans-tautomer species in the ground state with a lifetime of few microseconds. The experimental results correlate well with the theoretical approach, which suggests that PBT-NHTs proton transfer tautomer generated in the excited state undergoes intramolecular C1-C1' rotation to ∼100° between benzothiazole and phenyl moieties in which the energetics for the S1 and T1 states are nearly identical. As a result, the intersystem crossing between S1 and T1 states serves as a fast deactivation pathway for the excited-state cis-tautomer to channel into both cis- and trans-tautomer in their respective T1 states, followed by the dominant T1-S0 radiationless deactivation to populate the trans-tautomer in the ground state. The trans-tautomer species in the S0 state proceeds with intermolecular double proton transfer to regenerate the cis-normal form. An overall proton-transfer cycle describing the amino-type ESIPT and the subsequent isomerization processes is thus depicted in detail.

Lipase-catalyzed synthesis of palmitanilide: Kinetic model and antimicrobial activity study.

Enzymatic syntheses of fatty acid anilides are important owing to their wide range of industrial applications in detergents, shampoo, cosmetics, and surfactant formulations. The amidation reaction of Mucor miehei lipase Lipozyme IM20 was investigated for direct amidation of triacylglycerol in organic solvents. The process parameters (reaction temperature, substrate molar ratio, enzyme amount) were optimized to achieve the highest yield of anilide. The maximum yield of palmitanilide (88.9%) was achieved after 24 h of reaction at 40 °C at an enzyme concentration of 1.4% (70 mg). Kinetics of lipase-catalyzed amidation of aniline with tripalmitin has been investigated. The reaction rate could be described in terms of the Michaelis-Menten equation with a Ping-Pong Bi-Bi mechanism and competitive inhibition by both the substrates. The kinetic constants were estimated by using non-linear regression method using enzyme kinetic modules. The enzyme operational stability study showed that Lipozyme IM20 retained 38.1% of the initial activity for the synthesis of palmitanilide (even after repeated use for 48 h). Palmitanilide, a fatty acid amide, exhibited potent antimicrobial activity toward Bacillus cereus.

A new class of N-H proton transfer molecules: wide tautomer emission tuning from 590 nm to 770 nm via a facile, single site amino derivatization in 10-aminobenzo[h]quinoline.

Facile derivation of 10-aminobenzo[h]quinoline via replacing one of the N-H hydrogen atoms by various substituents generates a new series of excited-state intramolecular N-H proton-transfer molecules, for which the proton-transfer emission can be widely tuned from 590 nm to 770 nm simply by harnessing the electron-donating/withdrawing strength of the substituents.

Toward live-cell imaging of dopamine neurotransmission with fluorescent neurotransmitter analogues.

We report a novel 'fluorescent dopamine' that possesses essential features of natural dopamine. Our method is simple and is readily extended to monoamine neurotransmitters such as L-norepinephrine, serotonin and GABA, providing a more practical approach. Because of its compatibility with sensitive fluorescent measurements, we envisage that our approach will have a broad range of applications in neural research.

Harnessing Excited-State Intramolecular Proton-Transfer Reaction via a Series of Amino-Type Hydrogen-Bonding Molecules.

A series of new amino (NH)-type hydrogen-bonding (H-bonding) compounds comprising 2-(2'-aminophenyl)benzothiazole and its extensive derivatives were designed and synthesized. Unlike in the hydroxyl (OH)-type H-bonding systems, one of the amino hydrogens can be replaced with electron-donating/withdrawing groups. This, together with a versatile capability for modifying the parent moiety, makes feasible the comprehensive spectroscopy and dynamics studies of amino-type excited-state intramolecular proton transfer (ESIPT), which was previously inaccessible in the hydroxyl-type ESIPT systems. Empirical correlations were observed among the hydrogen-bonding strength (the N-H bond distances and proton acidity), ESIPT kinetics, and thermodynamics, demonstrating a trend that the stronger N-H···N hydrogen bond leads to a faster ESIPT, as experimentally observed, and a more exergonic reaction thermodynamics. Accordingly, ESIPT reaction can be harnessed for the first time from a highly endergonic type (i.e., prohibition) toward equilibrium with a measurable ESIPT rate and then to the highly exergonic, ultrafast ESIPT reaction within the same series of amino-type intramolecular H-bond system.

Diels-Alder reactions of three fused nitrogen-containing bicyclic enones: an efficient method toward novel nitrogen-containing angular tricyclic skeletons.

The syntheses of three fused bicyclic enones, including 1,2,6,6a-tetrahydro-1-tosyl-cyclopenta[b]pyrrol-3(5H)-one, 1,2,3,6,7,7a-hexahydro-4H-1-tosyl-cyclopenta[b]pyridin-4-one and 1,2,5,6,7,7a-hexahydro-3H-1-tosyl-indol-3-one, via anionic cyclization and Diels-Alder reactions with various dienes to construct novel nitrogen-containing angular tricyclic skeletons are described.

Intermolecular radical addition reactions of alpha-iodo cycloalkenones and a synthetic study of the formal synthesis of enantiopure fawcettimine.

The generation of alpha-carbonyl vinyl radicals from alpha-iodo cycloalkenones, the scope of their participation in intermolecular addition reactions with electron-withdrawing olefins are studied and a synthetic study of the formal synthesis of enantiopure fawcettimine using this reaction is described.

Promoting neoplastic transformation of humic acid in mouse epidermal JB6 Cl41 cells.

Humic acid (HA), a group of high-molecular weight polymer, resulting from the decomposition of organic matter has been implicated as a possible etiological factor for Blackfoot disease and cancer. In this study, we evaluate the promotion effect of HA on the transformation in mouse epidermal JB6 clone 41 (JB6 Cl41) cells that have been used to identify the tumor promoting activity of various compounds. Our preliminary assay demonstrated that JB6 Cl41 cells with the treatment of HA at the concentration of 100 microg/ml for 72 and 96 h significantly increased reactive oxygen species (ROS) as compared to the untreated control. In addition, the 48 h cultured cells with HA pretreatment for 48 h also increased ROS as compared to the untreated control. HA-pretreated cells develop highly scattered and spindle-shaped cells with few observable cell-cell contacts, and contain more filopodia. In vitro wound-healing assay showed that JB6 Cl41 cells with HA pretreatment increased the migrating growth. Furthermore, transformed foci of JB6 Cl41 cells following the HA pretreatment were observed after 6 weeks culture. In anchorage-independent growth assay, we found that HA promoted the colony formation and that colonies were inhibited by antioxidant N-acetyl cysteine (NAC). Our results suggest that HA may promote the transformation of epidermal cells and that this process is mediated by the generation of ROS.