DFT investigation of the DDQ-catalytic mechanism for constructing C-O bonds.

In this study, we investigated the photo-catalytic mechanisms for the construction of C-O bonds from arenes (benzene, 2',6'-dimethyl-[1,1'-biphenyl]-2-carboxylic acid, or 2,4-dichloro-1-fluorobenzene), catalyzed by 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ). All the structures for the Gibbs free surfaces were calculated at the M06-2X-D3/ma-def2-SVP level in the SMD solvent model. Also, TDDFT calculations of DDQ were performed at the PBE1PBE-D3/ma-def2-SVP level in the SMD solvent model. The computational results indicated that DDQ, serving as a photo-catalyst, would be excited under visible light of 450 nm, aligning well with experimental observations as reflected in the UV-vis spectrum. Gibbs free energy surface analyses of the three reactions suggested that the path involving 3DDQ* activating the reactant (-COOH, H2O, or CH3OH) is favorable. Additionally, the role of O2 was investigated, revealing that it could facilitate the recycling of DDQ by lowering the energy barrier for the conversion of the DDQH˙ radical (not DDQH2) into DDQ. The use of ρhole and ρele can reveal the photo-catalytic reaction and charge transfer processes, while localized orbital locator isosurfaces and electron spin density isosurface graphs were employed to analyze structures and elucidate the single electron distribution. These computational results offer valuable insights into the studied interactions and related processes, shedding light on the mechanisms governing C-O bond formation from arenes catalyzed by DDQ.

Mechanistic Study of 1,4-Benzodiazepine-2,5-diones from Diphenylamine and Diethyl 2-Phenylmalonate by Density Functional Theory.

The mechanisms for the reaction between diphenylamine and diethyl 2-phenylmalonate were investigated using M06-2X-D3/6-31+G(d,p) method and level, and the SMD model was applied to simulate the solvent effect. The computational results suggested that diphenylamine and diethyl 2-phenylmalonate can convert into 4-hydroxy-1,3-diphenylquinolin-2(1H)-one via a series of reactions (addition reaction, dealcoholization reaction, enolization reaction, dealcoholization reaction, ring-closure reaction, and H-shift reaction). And H2O, as the catalyst, can play an important role to promote these reactions. In the following reaction, there are two paths to yield the second product 3-chloro-1,3-diphenylquinoline-2,4(1H,3H)-dione and the computational results indicated that the first path (blue line) with the rate-determining step of 24.9 kcal/mol is favorable. With the participation of methanamine, a SN2 reaction happened and the third product 3-(methylamino)-1,3-diphenylquinoline-2,4(1H,3H)-dione had been yielded in the effect of methanamine or Cl anion. The analysis of Gibbs free energy surfaces shows that methanamine is better than Cl anion to extract the proton via an exothermic reaction. Finally, the third product 3-(methylamino)-1,3-diphenylquinoline-2,4(1H,3H)-dione would go through a ring-enlargement reaction, promoted by base (TMG or Triton B), to yield the final product. The computational results demonstrated that this reaction can release much energy with Triton B than that with TMG. And the energy of the highest point is 10.1 kcal/mol (16.8 kcal/mol), which can readily occur at the room temperature. The results could provide valuable insights into these types of interactions and related ones.

Insights into the Diels-Alder Reaction between 3-Vinylindoles and Methyleneindolinone without and with the Assistance of Hydrogen-Bonding Catalyst Bisthiourea: Mechanism, Origin of Stereoselectivity, and Role of Catalyst.

The Diels-Alder reaction between 3-vinylindoles and methyleneindolinone can proceed both under catalyst-free conditions and with bisthiourea as the catalyst. The reaction with bisthiourea is much faster and results in higher stereoselectivity of the product. The reaction mechanism, origin of stereoselectivity, and role of the catalyst were elaborated based on quantum mechanical calculations and theoretical methods of reactivity indices, NCI, QTAIM, and distortion/interaction models. In the uncatalyzed reaction, the two C-C bonds that are formed undergo conversion from noncovalent to covalent bonding via a concerted asynchronous mechanism. The weak intermolecular interactions formed in the transition state play important roles. The difference between the interaction and distortion energies is responsible for the stereoselectivity. In the catalyzed reaction, bisthiourea induces both the diene and dienophile to approach it via weak intermolecular interactions, which greatly lowers the energy barrier of the reaction and leads to the product with excellent stereoselectivity. The possible pathways of this reaction were explored, which suggested that the formation of the two C-C bonds goes through either a stepwise or concerted asynchronous mechanism. These results detail the reaction mechanism and shed light on both the significant role of the bisthiourea catalyst and the origin of stereoselectivity for this type of Diels-Alder reaction and related ones.

tert-Butyl nitrite (TBN) as the N atom source for the synthesis of substituted cinnolines with 2-vinylanilines and a relevant mechanism was studied.

A green method to synthesize cinnolines by 6π electrocyclic reaction with alkenyl amines and TBN has been developed. TBN plays a dual role both as a nitrogen atom source and an oxidant in this procedure. Relevant mechanism experiments reveal that the reaction proceeds through electrocyclic reaction and with diazo hydroxide as a key intermediate.

Approach for 2-(arylthio)imidazoles and imidazo[2,1-b]thiazoles from imidazo[2,1-b][1,3,4]thiadiazoles by ring-opening and -reconstruction.

A highly efficient one-pot synthesis of imidazo[2,1-b]thiazole derivatives has been developed and proceeds via a ring-opening and ring-closing reconstruction of imidazo[2,1-b][1,3,4]thiadiazoles with phenylacetylene in the presence of potassium tert-butoxide (t-BuOK) under very mild reaction conditions. A proposed mechanism is calculated computationally using a DFT method at the B3LYP/6-31+G(d,p) level. The imidazo[2,1-b][1,3,4]thiadiazoles are also successfully converted to a series of 2-(arylthio)-1H-imidazoles using aryl halide as a reactant and copper(ii) acetylacetonate (Cu(acac)2) as a catalyst under microwave irradiation conditions. The key features of these reactions are the use of readily available reagents, simple operation, the convenient utilization of new heterocyclic synthons, and a great variety of substrates with functional group compatibility.

Peptide-based colorimetric and fluorescent dual-functional probe for sequential detection of copper(â ¡) and cyanide ions and its application in real water samples, test strips and living cells.

A novel dual-functional peptide probe FLH based on fluorescent "on-off-on" strategy and colorimetric visualization method was designed and synthesized. This new probe exhibited highly selective and rapid detection of Cu2+ with significant fluorescent "turn-off" response, with a visible colorimetric change from yellow to orange. The combination ratio of FLH to Cu2+ (1:1) was determined using ESI-HRMS spectra and Job's plot. The fluorescent emission showed a good linear response (R2 = 0.9986) with a low detection limit of 1.5 nM. In addition, the FLH-Cu2+ complex displayed colorimetric changes and a fluorescent "off-on" response toward CN- over a wide pH range from 7 to 12. This detection behavior was observed within 20 s, with a limit of detection (LOD) for CN- at 12.7 nM. Based on stability and accuracy, FLH was next developed as dual-functional test strips, and was also successfully applied to detect Cu2+ and CN- in two actual water samples. More importantly, the cytotoxicity studies indicated that FLH had good biocompatibility and low toxicity, and was successfully utilized for monitoring Cu2+ and CN- in living cells through fluorescence imaging.

A novel peptide-based fluorescent probe with a large stokes shift for rapid and sequential detection of Cu2+ and CN- in aqueous systems and live cells.

A novel fluorescent probe (DSD) was reasonably designed and synthesized with dansyl-labeled dipeptide (Dan-Ser-Asp-NH2). DSD featured remarkably large Stokes shift (230 nm) and perfect water solubility, and exhibited high selectivity and rapid recognition toward Cu2+via fluorescence quenching. The detection limit of DSD for Cu2+ was 2.4 nM, indicated that DSD has excellent sensitivity. In addition, the stoichiometry between DSD and Cu2+ were detected as 1:1 by fluorescence titration, Job's plot and ESI-HRMS data. As designed, DSD-Cu2+ system was able to sequentially detect CN- according to the displacement approach with fluorescence "off-on" response, and the detection limit for CN- was calculated to be 41.9 nM. Specifically, the response time of DSD with Cu2+ and CN- was less than 40 s, which rendered it suitable for real time detection in actual water samples. In addition, with the alternate addition of Cu2+ and CN-, the reversible cycles could be repeated for at least 10 times, indicated that DSD was a promising reversibility probe. DSD showed low toxicity and good biocompatibility, and was successfully applied to detect Cu2+ and CN- in living cells.

A fluorescent dansyl-based peptide probe for highly selective and sensitive detect Cd2+ ions and its application in living cell imaging.

We reported a novel and readily synthesized fluorescent "turn-on" probe L (Dansyl-Glu-Pro-Gly-Cys) based on dansyl group combine tetrapeptide. The probe L exhibited highly sensitive fluorescent recognition to Cd2+ ions in HEPES buffer solutions (10.0 mM, pH 7.4). The 2:1 binding stoichiometry of L with Cd2+ were determined based on fluorescence titration and the Job's plot investigation. The competitive experiments were found to be highly selective for the Cd2+ ions even in the existence of excess competing metal ions including Zn2+, Pb2+, Hg2+ and Cu2+ ions. The binding constant of the complex L-Cd was calculated to be 5.18 × 1010 M-2, and showed great affinity compared to other probes. In addition, the detection limit of the probe L for Cd2+ ions was calculated to be 45 nM, which presented a pronounced sensitivity toward Cd2+ ions. Most importantly, the probe L had wide range of pH and good biocompatibility, and were successfully applied to selectively detected Cd2+ ions within pH range of 7-12 and bioimaging studies in live cells.

CuH-Catalyzed Asymmetric 1,6-Conjugate Reduction of p-Quinone Methides: Enantioselective Synthesis of Triarylmethanes and 1,1,2-Triarylethanes.

The first copper hydride (CuH)-catalyzed asymmetric 1,6-conjugate reduction of p-quinone methides is reported. This protocol provides a new method to access a variety of triarylmethanes and 1,1,2-triarylethanes in good yields with excellent enantioselectivities and broad functional group tolerance.

High selective and sensitive detection of Zn(II) using tetrapeptide-based dansyl fluorescent chemosensor and its application in cell imaging.

The zinc ions (Zn2+) play extremely irreplaceable role in the organism and the environment, the design and synthesis of a biomolecule-based fluorescence chemosensor for the detection of Zn2+ with high sensitivity is very important. Herein, a novel tetrapeptide-based dansyl fluorescent "turn-on" response chemosensor (L) has been designed and synthesized by solid phase peptide synthesis (SPPS). As designed, L can detect Zn2+ ions with specifically and sensitively based on photo-induced electron transfer (PET) mechanism in 100% aqueous solutions, and other metal ions do not interfere with Zn2+ ions recognition. The stoichiometric ratio of L with Zn2+ ions was 2:1, which matches with fluorescence titration and Job-plot assay. In addition, the reversibility and circularly process of the detection of L was confirmed by adding bonding agent Na2EDTA. Moreover, L exhibits excellent biocompatibility and low biotoxicity with the limit of detection (LOD) for Zn2+ about 18 nM, and has been successfully utilized for fluorescence imaging of Zn2+ ions in living HeLa cells under physiological conditions.

DFT investigation on the metabolic mechanisms of theophylline by cytochrome P450 monooxygenase.

Theophylline, one of the most commonly used bronchodilators and respiratory stimulators for the treatment of acute and chronic asthmatic conditions, can cause permanent neurological damage through chronic or excessive ingestion. In this work, DFT calculation was performed to identify the metabolic mechanisms of theophylline by cytochrome P450 (CYP450) monooxygenase. Two main metabolic pathways were investigated, namely, N1- (path A) and N3- (path B) demethylations, which proceeded through N-methyl hydroxylation followed by the decomposition of the generated carbinolamine species. N-methyl hydroxylation involved a hydrogen atom transfer (HAT) mechanism, which can be generalized as the N-demethylation mechanism of xanthine derivatives. The energy gap between the low-spin double state (LS) and the high-spin quartet state (HS) was low (<1 kcal mol-1), indicating a two-state reactivity (TSR) mechanism. The generated carbinolamine species preferred to decompose through the adjacent heteroatom (O6 for path A and O2 for path B) mediated mechanism. Path B was kinetically more feasible than path A attributed to its relatively lower activation energy. 1-Methylxanthine therefore was the energetically favorable metabolite of theophylline. The observations obtained in the work were in agreement with the experimental observation, which can offer important implications for further pharmacological and clinic studies.

Regioregular and Regioirregular Poly(selenophene-perylene diimide) Acceptors for Polymer-Polymer Solar Cells.

We report two new regioregular and regioirregular model copolymer acceptors based on selenophene and perylenetetracarboxylic diimide moieties, respectively, named RR-P(SePDI) and RI-P(SePDI), which were synthesized to study how regioregularity impacts the properties of resulting polymers. The structural regioregularity impact on the performance of polymer-polymer solar cells (PPSCs) was highlighted. Both the copolymer acceptors displayed similar optoelectronic properties. The regioregular RR-P(SePDI) exhibited better and balance bulk charge-transport capability than regioirregular RI-P(SePDI) in active layer films. The typical PPSCs based on the regioirregular RI-P(SePDI) copolymer acceptor and the PTB7-Th polymer donor afforded average power conversion efficiencies (PCEs) of about 5.3%. Importantly, reasonably improved average PCEs of about 6.2% were provided by the blend active layer of new regioregular RR-P(SePDI) and PTB7-Th. These results highlight the significant and efficient strategy of rational control regioregularity of the polymer backbone to gain high PCE values in perylene diimide-based PPSCs.

Linear σ-hole⋯CO⋯σ-hole intermolecular interactions between carbon monoxide and dihalogen molecules XY (X, Y=Cl, Br).

Carbon monoxide can interact with two dihalogen molecules XY (X, Y=Cl, Br) in the form of X(Y)⋯COX(Y)⋯CO⋯X(Y)X(Y) trimeric complex, and their nature and characteristics were investigated at MP2/aug-cc-pVDZ level without and with counterpoise method, together with single point calculations at CCSD(T)/aug-cc-pVDZ level. The optimized geometries, stretching modes and interaction energies of a series of X(Y)⋯COX(Y)⋯CO⋯X(Y)X(Y) trimeric complexes were obtained and discussed. The cooperativity in these complexes was evaluated. EDA analyses reveal that the electrostatic interaction is the dominant net driving force in each trimer, but the contributions of other interactions like exchange, dispersion and polarization interactions are also important. QTAIM and NCI analyses confirm the existence of attractive halogen-bonding interactions. Additionally, EDDMF analysis was employed for the component dimers of these trimers, which indicates that the formation of halogen-bonding interactions is closely related to the charge shift and the rearrangement of electronic density in the formation of these complexes. The results would provide valuable insight into for these linear halogen bonds.

Preparation of α-Acyloxy Ketones via Visible-Light-Driven Aerobic Oxo-Acyloxylation of Olefins with Carboxylic Acids.

We developed a visible-light driven oxo-acyloxylation of aryl alkenes with carboxylic acids and molecular oxygen. A metal-free photoredox system, consisting of an acridinium photocatalyst, an organic base, and molecular sieve (MS) 4 Å, promotes chemoselective aerobic photooxidation of aryl alkenes. This approach may provide a green, practical, and metal-free protocol for a wide range of α-acyloxy ketones.