Photooxidation of Tryptophan: O2(1Δg) versus Electron-Transfer Pathway

Abstract— Tris (2,2'-bipyridyl)ruthenium(II)chloride hexahydrate (Ru[bpy]₃²+) free in solution and adsorbed onto antimony-doped SnO₂ colloidal particles was used as a photosensitizer for a comparison of the O₂(¹Δ_g) and electron-transfer-mediated photooxidation of tryptophan (TRP), respectively. Quenching of excited Ru(bpy)₃²+ by O₂(³σ_g^?) in an aerated aqueous solution leads only to the formation of O₂(¹Δ_g) (φ₄= 0.18) and this compound was used as a type II photosensitizer. Excitation of Ru(bpy)₃²+ adsorbed onto Sb/SnO₂ results in a fast injection of an electron into the conduction band of the semiconductor and accordingly to the formation of Ru(bpy)₃²+ and was used for the sensitization of the electron-transfer-mediated photooxidation. The Ru(bpy)₃³+ is reduced by TRP with a bimolecular rate constant k_Q= 5.9 × 10⁸M^?1 s^?1, while O₂(¹Δ_g) is quenched by TRP with k_t= 7.1 × 10⁷M^?1 s^?1 (chemical + physical quenching). Relative rate constants for the photooxidation of TRP (k_c) via both pathways were determined using fluorescence emission spectroscopy. With N_p, the rate of photons absorbed, being constant for both pathways we obtained k_c= (372/N_p) M^?1 s^?1 for the O₂(¹Δ_g) pathway and k_c≥ (25013/N_p) M^?1 s^?1 for the electron-transfer pathway, respectively. Thus the photooxidation of Trp is more than two orders of magnitude more efficient when it is initiated by electron transfer than when initiated by O₂(¹Δ_g).     

Alkene Isomerization–Hydroarylation Tandem Catalysis: Indole C2‐Alkylation with Aryl‐Substituted Alkenes Leading to 1,1‐Diarylalkanes

A cobalt‐N‐heterocyclic carbene catalyst generated from CoBr₂, imidazolium salt, and cyclohexylmagnesium bromide was found to promote the imine‐directed C2‐alkylation of indoles with nonconjugated arylalkenes through a tandem alkene isomerization–hydroarylation process, affording 1,1‐diarylalkanes with exclusive regioselectivity. The feasibility of the tandem catalysis was demonstrated for allyl‐, homoallyl‐, and bishomoallylbenzene derivatives. The catalytic system is also applicable to a variety of β‐substituted styrene derivatives. Mechanistic experiments using deuterium‐labeled indole substrate and Grignard reagent provided insight into the cobalt‐mediated C? H activation step, which likely involves exchange of the C2‐hydrogen atom of the former and the β‐hydrogen atoms of the latter.     

A Cyanine Photooxidation/β‐Elimination Sequence Enables Near‐infrared Uncaging of Aryl Amine Payloads

Uncaging strategies that use near‐infrared wavelengths can enable the highly targeted delivery of biomolecules in complex settings. Many methods, including an approach we developed using cyanine photooxidation, are limited to phenol‐containing payloads. Given the critical role of amines in diverse biological processes, we sought to use cyanine photooxidation to initiate the release of aryl amines. Heptamethine cyanines substituted with an aryl amine at the C4′ position undergo only inefficient release, likely due electronic factors. We then pursued the hypothesis that the carbonyl products derived from cyanine photooxidation could undergo efficient β‐elimination. After examining both symmetrical and unsymmetrical scaffolds, we identify a merocyanine substituted with indolenine and coumarin heterocycles that undergoes efficient photooxidation and aniline uncaging. In total, these studies provide a new scheme—cyanine photooxidation followed by β‐elimination—through which to design photocages with efficient uncaging properties.     

Using Morita–Baylis–Hillman acetates of 2‐azidobenzaldehydes for the synthesis of 2‐alkoxy‐3‐cyanomethylquinolines and alkyl quinoline‐3‐carboxylates

A simple method for the synthesis of several 2‐alkoxy‐3‐cyanomethylquinolines and alkyl quinoline‐3‐carboxylates using iminophosphorane‐mediated cyclization reactions of 3‐(2‐azidophenyl)‐2‐cyanomethylpropenoates and 3‐(2‐azidophenyl)‐2‐nitromethylpropenoates has been developed. These compounds were readily obtained from the Morita–Baylis–Hillman acetates of 2‐azidobenzaldehydes using potassium cyanide or sodium nitrite, respectively. J. Heterocyclic Chem., (2011)     

Investigation of Diels–Alder Reaction of 7‐Substituted 4‐Styrylcoumarins with Symmetrical Dienophiles Leading to 3,4‐Annulated Coumarins

The thermal [4 + 2] cycloaddition reaction of 7‐substituted 4‐styrylcoumarins with N‐phenylmaleimide and tetracyanoethylene in nitrobenzene under reflux conditions rapidly gives 3,4‐annulated coumarins as the Diels–Alder adducts. The position of the surviving double bond was determined on the basis of NMR and supported by energies of the possible structures. The effects of the 7‐substituent and the solvent on the reaction were studied.     

Acyclic Branched α‐Fluoro Ketones for the Direct Asymmetric Mannich Reaction Leading to the Synthesis of β‐Tetrasubstituted β‐Fluoro Amines

The preparation of acyclic β‐fluoro amines bearing tetrasubstituted fluorine stereocenters is described via a direct Zn/ProPhenol‐catalyzed Mannich reaction. The reaction utilizes branched vinyl or alkynyl α‐fluoro ketones that can be coupled with a range of aryl, heteroaryl, vinyl, or cyclopropyl aldimines in high yield and with excellent diastereo‐ (up to >20:1) and enantioselectivity (up to 99 %). The use of readily cleaved tert‐butoxycarbonyl (Boc) or carboxybenzyl (Cbz) imine protecting groups adds utility to the reaction by allowing for easy access to the free amine products under mild and chemoselective reaction conditions.     

A New Iodonium Ylide‐Based Three‐Component Reaction Leading to 2‐Spirosubstituted Dihydrofurans under Microwave Irradiation

A new iodonium ylide‐based three‐component reaction for the synthesis of highly functionalized 2‐spirosubstituted dihydrofurans starting from readily available common reactants has been developed under microwave irradiation. The procedure is facile, avoiding time‐consuming and costly syntheses, tedious work‐up and purifications of precursors as well as protection/deprotection of functional groups. This method is very efficient because of short reaction times and easy work‐up and provides an efficient strategy for the construction of the polysubstituted spiro dihydrofuran skeleton.     

Two‐ and Three‐Component Reactions Leading to New Enamines Derived from 2,3‐Dicyanobut‐2‐enoates

The three‐component reactions of 1‐azabicyclo[1.1.0]butanes 1 , dicyanofumarates (E)‐ 5 , and MeOH or morpholine yielded azetidine enamines 8 and 9 with the cis‐orientation of the ester groups at the C?C bond ((E)‐configuration; Schemes 3 and 4). The structures of 8a and 9d were confirmed by X‐ray crystallography. The formation of the products is explained via the nucleophilic addition of 1 onto (E)‐ 5 , leading to a zwitterion of type 7 (Scheme 2), which is subsequently trapped by MeOH or morpholine ( 10a ), followed by elimination of HCN. Similarly, two‐component reactions between secondary amines 10a – 10c and (E)‐ 5 gave products 12 with an (E)‐enamine structure and (Z)‐oriented ester groups. On the other hand, two‐component reactions involving primary amines 10d – 10f or NH₃ led to the formation of the corresponding (Z)‐enamines, in which the (E)‐orientation of ester groups was established.     

MnO2‐TiO2 Nanocomposite and 2‐(3,4‐Dihydroxyphenethyl) Isoindoline‐1,3‐Dione as an Electrochemical Platform for the Concurrent Determination of Cysteine,Tryptophan and Uric Acid

A novel modified carbon paste electrode (CPE) based on an MnO₂‐TiO₂ nanocomposite and 2‐(3,4 dihydroxyphenethyl) isoindoline‐1,3‐dione (DPID) as the modifier for the simultaneous analysis of cysteine (Cys), tryptophan (Trp) and uric acid (UA), as three key biochemicals present in human body. The MnO₂/TiO₂ nanocomposite was synthesized through a chemical co‐precipitation approach and the resulting electrode (MnO₂‐TiO₂/DPID/CPE) was used for studying the electrochemical oxidation of cysteine (Cys), tryptophan (Trp) and uric acid. As opposed to conventional CPEs, the oxidation peak potential of cysteine on MnO₂‐TiO₂/DPID/CPE had a 600.0 mV decrease in overpotential and could be observed at 30.0 mV, and the signals were linear from 0.025 to 200.0 μM, and a lower detection limit of 0.013 μM was reached. The MnO₂‐TiO₂/DPID/CPE was satisfactorily used for the concurrent analysis of Cys, Trp and UA in pharmaceutical and biological samples.     

Off‐line 2‐D RPLC/RPLC method for separation of components in Dalbergia odorifera T. Chen

An off‐line 2‐D RPLC/RPLC system incorporating a β‐CD based column and a BEH C18 column was developed in the separation of components in Dalbergia odorifera T. Chen. (Jiang Xiang). Both orthogonality and van Deemter curves of the two columns were investigated. The orthogonality was about 57%, which was evaluated with 40 standard solutes. Optimized column efficiency could be achieved under optimal linear velocity (0.04 cm/s) on the CD column or under high linear velocity (0.32 cm/s) on the BEH C18 column. With the 2‐D LC system, totally 637 peaks were separated in 114 fractions from the extraction of Jiang Xiang. Meanwhile, 19 flavanoids were tentatively identified from 114 fractions with Q‐TOF MS. The results demonstrated the separation power of this 2‐D LC system and further proved the high orthogonality between CD and C18 columns.     

A zinc–lithium complex of 4,7‐bis(2‐aminoethyl)‐1,4,7‐triazacyclononane‐1‐acetate

The asymmetric unit of {[4,7‐bis(2‐amino­ethyl)‐1,4,7‐tri­aza­cyclo­nonan‐1‐yl]acetato}zinc(II) triaqua{μ‐[4,7‐bis(2‐amino­ethyl)‐1,4,7‐tri­aza­cyclo­nonan‐1‐yl]acetato}lithium(I)zinc(II) chloride diperchlorate, [Zn(C₁₂H₂₆N₅O₂)][LiZn(C₁₂H₂₆N₅O₂)(H₂O)₃]Cl(ClO₄)₂, obtained from the reaction between the lithium salt of 4,7‐bis(2‐amino­ethyl)‐1,4,7‐tri­aza­cyclo­nonane‐1‐acetate and Zn(ClO₄)₂, contains two Zn^II complexes in which each Zn^II ion is six‐coordinated by five N‐atom donors and one O‐­atom donor from the ligand. One carboxyl­ate O‐atom donor is not involved in coordination to a Zn^II atom, but coordinates to an Li⁺ ion, the tetrahedral geometry of Li⁺ being completed by three water mol­ecules. The two complexes are linked via a hydrogen bond between a primary amine N—H group and the carboxyl­ate‐O atom not involved in coordination to a metal.     

Possible neighbouring group participation of a nitro‐group in the conversion of 3‐hydroxymethyl‐2‐(2‐nitrophenyl)‐1,2,3,4‐tetrahydroisoquinoline into its 3‐chloromethyl derivative

The alcohol 12 reacted with 4‐toluenesulfonyl chloride in boiling dichloromethane solution to give the chlorinated product 13 rather than the expected tosylate 3 by a mechanism that could involve neighbouring group participation of the nitro‐substituent. In contrast, the isomeric alcohol 15 reacted normally with 4‐toluenesulfonyl chloride giving the tosylate 16 under similar conditions.     

Coupling of the Decarboxylation of 2‐Cyano‐2‐phenylpropanoic Acid to Large‐Amplitude Motions: A Convenient Fuel for an Acid–Base‐Operated Molecular Switch

The decarboxylation of 2‐cyano‐2‐phenylpropanoic acid is fast and quantitative when carried out in the presence of 1 molar equivalent of a [2]catenane composed of two identical macrocycles incorporating a 1,10‐phenanthroline unit in their backbone. When decarboxylation is over, all of the catenane molecules have experienced large‐amplitude motions from neutral to protonated catenane, and back again to the neutral form, so that they are ready to perform another cycle. This study provides the first example of the cyclic operation of a molecular switch at the sole expenses of the energy supplied by the substrate undergoing chemical transformation, without recourse to additional stimuli.     

A Method for Evaluating the Level of Soluble β‐Amyloid(1–40/1–42) in Alzheimer’s Disease Based on the Binding of Gelsolin to β‐Amyloid Peptides

In the present work, a new electrochemical strategy for the sensitive and specific detection of soluble β‐amyloid Aβ_{(1–40/1–42)} peptides in a rat model of Alzheimer’s disease (AD) is described. In contrast to previous antibody‐based methods, β‐amyloid_{(1–40/1–42)} was quantified based on its binding to gelsolin, a secretory protein present in the cerebrospinal fluid (CSF) and plasma. The level of soluble β‐amyloid peptides in the CSF and various brain regions were found with this method to be lower in rats with AD than in normal rats.