Zhuofeng Ke

Dinuclear Zn(II) complex catalyzed phosphodiester cleavage proceeds via a concerted mechanism: A density functional theory study

Density functional theory (DFT) calculations were used to study the mechanism for the cleavage reaction of the RNA analogue HpPNP (HpPNP = 2-hydroxypropyl-4-nitrophenyl phosphate) catalyzed by the dinuclear Zn(II) complex of 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane (Zn(2)(L(2)O)). We present a binding mode in which each terminal phosphoryl oxygen atom binds to one zinc center, respectively, and the nucleophilic 2-hydroxypropyl group coordinates to one of the zinc ions, while the hydroxide from deprotonation of a water molecule coordinates to the other zinc ion. Our calculations found a concerted mechanism for the HpPNP cleavage with a 16.5 kcal/mol reaction barrier. An alternative proposed stepwise mechanism through a pentavalent oxyphosphorane dianion reaction intermediate for the HpPNP cleavage was found to be less feasible with a significantly higher energy barrier. In this stepwise mechanism, the deprotonation of the nucleophilic 2-hydroxypropyl group is accompanied with nucleophilic attack in the rate-determining step. Calculations of the nucleophile (18)O kinetic isotope effect (KIE) and leaving (18)O KIE for the concerted mechanism are in reasonably good agreement with the experimental values. Our results indicate a specific-base catalysis mechanism takes place in which the deprotonation of the nucleophilic 2-hydroxypropyl group occurs in a pre-equilibrium step followed by a nucleophilic attack on the phosphorus center. Detailed comparison of the geometric and electronic structure for the HpPNP cleavage reaction mechanisms in the presence/absence of catalyst revealed that the catalyst significantly altered the determining-step transition state to become far more associative or tight, that is, bond formation to the nucleophile was remarkably more advanced than leaving group bond fission in the catalyzed mechanism. Our results are consistent with and provide a reliable interpretation for the experimental observations that suggest the reaction occurs by a concerted mechanism (see Humphry, T.; Iyer, S.; Iranzo, O.; Morrow, J. R.; Richard, J. P.; Paneth, P.; Hengge, A. C. J. Am. Chem. Soc. 2008, 130, 17858-17866) and has a specific-base catalysis character (see Yang, M.-Y.; Iranzo, O.; Richard, J. P.; Morrow, J. R. J. Am. Chem. Soc. 2005, 127, 1064-1065).

Histone-Deacetylase-Targeted Fluorescent Ruthenium(II) Polypyridyl Complexes as Potent Anticancer Agents

Histone deacetylases inhibitors (HDACis) have gained much attention as a new class of anticancer agents in recent years. Herein, we report a series of fluorescent ruthenium(II) complexes containing N(1)-hydroxy-N(8)-(1,10-phenanthrolin-5-yl)octanediamide (L), a suberoylanilide hydroxamic acid (SAHA) derivative, as a ligand. As expected, these complexes show interesting chemiphysical properties, including relatively high quantum yields, large Stokes shifts, and long emission lifetimes. The in vitro inhibitory effect of the most effective drug, [Ru(DIP)2L](PF6)2 (3; DIP: 4,7-diphenyl-1,10-phenanthroline), on histone deacetylases (HDACs) is approximately equivalent in activity to that of SAHA, and treatment with complex 3 results in increased levels of the acetylated histone H3. Complex 3 is highly active against a panel of human cancer cell lines, whereas it shows relatively much lower toxicity to normal cells. Further mechanism studies show that complex 3 can elicit cell cycle arrest and induce apoptosis through mitochondria-related pathways and the production of reactive oxygen species. These data suggest that these fluorescent ruthenium(II)-HDACi conjugates may represent a promising class of anticancer agents for potential dual imaging and therapeutic applications targeting HDACs.

Mechanism and Enantioselectivity of Dirhodium-Catalyzed Intramolecular C–H Amination of Sulfamate

The mechanisms and enantioselectivities of the dirhodium (Rh2L4, L = formate, N-methylformamide, S-nap)-catalyzed intramolecular C-H aminations of 3-phenylpropylsulfamate ester have been investigated in detail with BPW91 density functional theory computations. The reactions catalyzed by the Rh2(II,II) catalysts start from the oxidation of the Rh2(II,II) dimer to a triplet mixed-valent Rh2(II,III)-nitrene radical, which should facilitate radical H-atom abstraction. However, in the Rh2(formate)4-promoted reaction, as a result of a minimum-energy crossing point (MECP) between the singlet and triplet profiles, a direct C-H bond insertion is postulated. The Rh2(N-methylformamide)4 reaction exhibits quite different mechanistic characteristics, taking place via a two-step process involving (i) intramolecular H-abstraction on the triplet profile to generate a diradical intermediate and (ii) C-N formation by intersystem crossing from the triplet state to the open-shell singlet state. The stepwise mechanism was found to hold also in the reaction of 3-phenylpropylsulfamate ester catalyzed by Rh2(S-nap)4. Furthermore, the diradical intermediate also constitutes the starting point for competition steps involving enantioselectivity, which is determined by the C-N formation open-shell singlet transition state. This mechanistic proposal is supported by the calculated enantiomeric excess (94.2% ee) with the absolute stereochemistry of the product as R, in good agreement with the experimental results (92.0% ee).

Nonplanar Organic Sensitizers Featuring a Tetraphenylethene Structure and Double Electron-Withdrawing Anchoring Groups

Two metal-free organic sensitizers containing two N,N-diethylaniline (DEA) moieties and a twisted 1,1,2,2-tetraphenylethene (TPE) structure, dye SD with one anchoring group and dye DD with two anchoring groups, were synthesized and applied in dye-sensitized solar cells (DSSCs). The introduction of a nonplanar TPE structure was used to form a series of propeller-like structures and reduce the tendency of dyes to randomly aggregate on TiO2 surface, but without importing an aggregation-induced emission (AIE) property. The thermal stabilities, UV-vis absorption spectra, electrochemical properties, and photovoltaic parameters of DSSCs with these two dyes were systematically studied and compared with each other. The overall conversion efficiencies (η) of 4.56% for dye SD and 6.08% for dye DD were obtained under AM 1.5 G irradiation.

A Highly Selective and Robust Co(II)-Based Homogeneous Catalyst for Reduction of CO2 to CO in CH3CN/H2O Solution Driven by Visible Light

Visible-light driven reduction of CO2 into chemical fuels has attracted enormous interest in the production of sustainable energy and reversal of the global warming trend. The main challenge in this field is the development of efficient, selective, and economic photocatalysts. Herein, we report a Co(II)-based homogeneous catalyst, [Co(NTB)CH3CN](ClO4)2 (1, NTB = tris(benzimidazolyl-2-methyl)amine), which shows high selectivity and stability for the catalytic reduction of CO2 to CO in a water-containing system driven by visible light, with turnover number (TON) and turnover frequency (TOF) values of 1179 and 0.032 s-1, respectively, and selectivity to CO of 97%. The high catalytic activity of 1 for photochemical CO2-to-CO conversion is supported by the results of electrochemical investigations and DFT calculations.

Removal of NO with silicene: a DFT investigation

Removing or reducing NO is meaningful for environment protection. Herein, the investigation of the probability of NO reduction on silicene is presented utilizing DFT calculations. Two mechanisms for NO reduction on silicene are provided: a direct dissociation mechanism and a dimer mechanism. The direct dissociation mechanism is characterized as the direct breaking of the N–O bond. The calculated potential energy surfaces show that the total energy barrier in the favored direct dissociation pathway is 0.466 eV. On the other hand, the dimer mechanism is identified to undergo a (NO)2 dimer formation on silicene, which then decomposes into N2O + Oad or N2 + 2Oad. The (NO)2 dimer formation on silicene is found to be feasible both in thermodynamics and kinetics. The formation energy barriers for (NO)2 dimer are lower than 0.231 eV. The calculation results indicate that the (NO)2 dimers can be readily reduced into N2O or N2. The energy barriers in the favored decomposition pathways to produce N2O are quite low (<0.032 eV). The energy barrier for the release of N2 is calculated to be 0.156 eV. The further reduction of N2O to N2 on silicene is also investigated. The results indicate it is easy to reduce N2O to N2 with an energy barrier of only 0.445 eV. NO reduction on silicene hence prefers to generate N2 via the dimer mechanism when compared to the direct dissociation. NO reduction on silicene with silicane as substrate is further proved to proceed via the same reduction mechanism as compared with the free-standing model. Hence, our results presented here suggest that silicene can be a potential material in NO removal, which will reduce NO into environmentally-friendly gases.

Density functional theory study of the mechanism of zinc carbenoid promoted cyclopropanation of allenamides

The mono- and bis-cyclopropanation of allenamides with the zinc carbenoid Zn(CH2Cl)2 have been studied using density functional theory calculations employing the M06 functional. The monomeric and dimeric precursor complexes were both constructed to model the reaction processes. In the monomeric reaction, the formation of the endo-monocyclopropyl species takes place via a methylene transfer pathway rather than a carbometalation pathway. The formation of the exo-monocyclopropyl species does not readily occur via a methylene transfer pathway due to a high activation barrier. The corresponding carbometalation pathway was not able to be found. Following the monocyclopropanation step, the biscyclopropanation of the endo-monocyclopropyl species is facile to form amidospiro[2.2]pentane. In the aggregation model, the allenamides and the zinc carbenoid form a dimer aggregate that is then followed by two pathways. One pathway takes place via transition states inside the aggregate structure (denoted here as a closed-mode process) while the other pathway introduces another zinc carbenoid molecule from outside the aggregation species (denoted here as an open-mode process). The aggregate mechanisms are not favored because the dimeric reactant of the open-mode process is not stable to coexist with the monomer and the activation barriers of the two aggregate pathways are higher than those of the monomeric pathways. The calculation results show that the key factors in the reaction mechanisms are the co-planarity of the allenic moiety with the oxazolidinone ring, the torsional strain in the butterfly-type transition state, the ring strain in the substrate–carbenoid complexes and the coordination between the carbenoid-Zn and O(CO) atoms and other long-distance interactions.

Enantioselective Hydrolysis of Amino Acid Esters Promoted by Bis(β-cyclodextrin) Copper Complexes

It is challenging to create artificial catalysts that approach enzymes with regard to catalytic efficiency and selectivity. The enantioselective catalysis ranks the privileged characteristic of enzymatic transformations. Here, we report two pyridine-linked bis(β-cyclodextrin) (bisCD) copper(II) complexes that enantioselectively hydrolyse chiral esters. Hydrolytic kinetic resolution of three pairs of amino acid ester enantiomers (S1–S3) at neutral pH indicated that the “back-to-back” bisCD complex CuL1 favoured higher catalytic efficiency and more pronounced enantioselectivity than the “face-to-face” complex CuL2. The best enantioselectivity was observed for N-Boc-phenylalanine 4-nitrophenyl ester (S2) enantiomers promoted by CuL1, which exhibited an enantiomer selectivity of 15.7. We observed preferential hydrolysis of L-S2 by CuL1, even in racemic S2, through chiral high-performance liquid chromatography (HPLC). We demonstrated that the enantioselective hydrolysis was related to the cooperative roles of the intramolecular flanking chiral CD cavities with the coordinated copper ion, according to the results of electrospray ionization mass spectrometry (ESI-MS), inhibition experiments, rotating-frame nuclear Overhauser effect spectroscopy (ROESY), and theoretical calculations. Although the catalytic parameters lag behind the level of enzymatic transformation, this study confirms the cooperative effect of the first and second coordination spheres of artificial catalysts in enantioselectivity and provides hints that may guide future explorations of enzyme mimics.

Further insight into the electrocatalytic water oxidation by macrocyclic nickel(II) complexes: the influence of steric effect on catalytic activity

The development of efficient, robust and economical water oxidation catalysts (WOCs) remains a key challenge for water splitting. Herein, three macrocyclic nickel(II) complexes with four, six and eight methyl groups in the ligands have been utilized as homogeneous electrocatalysts for water oxidation in aqueous phosphate buffer at pH 7.0, in which the catalyst with eight methyl groups exhibits the highest catalytic activity, with a large current density of 1.0 mA cm−2 at 1.55 V vs. NHE (750 mV overpotential) in long-term electrolysis. The results of electrochemistry, UV-vis spectroelectrochemistry and DFT calculations suggest that the axially oriented methyl groups in the macrocyclic ligands with eight and six methyl groups can impose a steric effect on the axial position of the NiIII center, which not only results in higher NiIII/II oxidation potentials but also suppresses the axial coordination of phosphate anions with the NiIII center to achieve better catalytic performance. Such a steric effect in homogeneous WOCs has not been reported so far.

Frustrated Lewis Pair Catalyzed C–H Activation of Heteroarenes: A Stepwise Carbene Mechanism Due to Distance Effect

This study presents new mechanistic insights into the frustrated Lewis pairs (FLPs) catalyzed C-H activation of heteroarenes. Besides the generally accepted concerted C-H activation, a novel stepwise carbene type pathway is proposed as an alternative mechanism. The reaction mechanisms can be varied by tuning the distance between Lewis acid and Lewis base due to catalyst-substrate match. These results should expand the understanding of the structure and function of FLPs for catalyzed C-H activation.