Electron transfer activation of chromopyrrolic acid by cytochrome p450 en route to the formation of an antitumor indolocarbazole derivative: theory supports experiment

QM/MM calculations support experiment and show that StaP is a P450 that functions like a peroxidase: its active species is the one-electron-reduced Cpd II species with a radical on CPA, by analogy to cytochrome c peroxidase (CcP), and its reaction with the substrate proceeds by overall proton-coupled electron transfer (PCET), in analogy to the corresponding mechanism in horseradish peroxidase (HRP). The electron transfer is enabled by His250, the presence of carboxylate groups in CPA, and by the H-bonding network that tunes the energetic of the process. Theory supports experiment but reveals some novel aspects of this unusual P450.     

Photoinduced tandem three-component coupling of propanedinitrile, 2,5-dimethylhexa-2,4-diene, and cyanoarenes

A tandem three-component coupling photoreaction proceeds upon photoirradiation of MeCN/H2O solutions containing propanedinitrile (1, malononitrile), 2,5-dimethylhexa-2,4-diene (2), and polycyanoarenes in the presence of phenanthrene and carbonate, leading to selective alpha-monoalkylation of 1. The reaction proceeds via photo-NOCAS (Nucleophile-Olefin Combination, Aromatic Substitution) type mechanism: nucleophilic attack of the anion of 1 to photogenerated 2(*+) is followed by ipso-substitution on the radical anion of the polycyanoarene. It advances under mild, safe, and environmentally friendly conditions such as proceeding at ambient temperature without metals and halogens, and in the presence of weak base. The reaction also represents a novel and metal-free cross-coupling reaction that leads to ipso-substitution on polycyanoarene via aryl-cyano bond cleavage. In addition, the reaction is a rare example of introducing carbon nucleophile in the photoinduced electron transfer reaction, except that of cyanide ion.     

Anti-Stokes Luminescence in Multi-Resonance-Type Thermally-Activated Delayed Fluorescence Molecules

Photon-upconversion in organic molecular systems is one of the promising technologies for future energy harvesting systems because these systems can generate excitons that possess higher energy than excitation energy. The photon-upconversion caused by absorbing ambient heat as additional energy is particularly interesting because it could ideally provide a light-driving cooling system. However, only a few organic molecular systems have been reported. Here, we report the anti-Stokes photoluminescence (ASPL) derived from hot-band absorption in a series of multi-resonance-type thermally-activated delayed fluorescence (MR-TADF) molecules. The MR-TADF molecules exhibited an anti-Stokes shift of approximately 0.1 eV with a high PL quantum yield in the solution state. The anti-Stokes shift corresponded well to the 1–0 vibration transition from the ground state to the excited singlet state, and we further evaluated a correlation between the activation energy for the ASPL intensity and the TADF process. Our demonstration underlines that MR-TADF molecules have become a novel class of ASPL materials for various future applications, such as light-driving cooling systems.     

Multidynamic Crystalline Molecular Rotors Comprising an N-Heterocyclic Carbene Binuclear Au(I) Complex Bearing Multiple Rotators

We report multidynamic molecular rotations in crystals using a concave-shape N-heterocyclic carbene (NHC) binuclear Au(I) complex rotor bearing pyrazine and tetrahydrofuran (THF) molecules as multicomponent rotators. Single-crystal X-ray diffraction (XRD) measurements revealed that two THF molecules are located near the central pyrazine encapsulated by two bulky NHC ligands. From ²H solid-state NMR analysis, it was observed that the pyrazine rotated in a 2-fold site exchange with a 180° rotational angle and a 31 kJ mol⁻¹ energy barrier, while the THF molecules showed a 23°-38° libration with a lower energy barrier (14 kJ mol⁻¹). Interestingly, the pyrazine rotation was accelerated when the THF molecules rotated in fast site exchange with a large angle of libration, suggesting that the rotators exhibit multidynamics in a correlated manner.     

Channel-selective independent sorption and collection of hydrophilic and hydrophobic molecules by Cs2[Cr3O(OOCC2H5)6(H2O)3]2[alpha-SiW12O40] ionic crystal

An ionic crystal of Cs2[Cr3O(OOCC2H5)6(H2O)3]2[alpha-SiW12O40].4H2O 1a with hydrophilic and hydrophobic channels has been designed and successfully synthesized. The guest-free phase 1b sorbs dichloromethane and water in the hydrophobic and hydrophilic channels, respectively. The rate and equilibrium amount of the dichloromethane sorption into the hydrophobic channel and those of water into the hydrophilic channel were independent of each other. The sorption properties can be applied to the channel-selective sorption and collection of hydrophobic (dichloromethane) and hydrophilic (water) molecules from the mixture.     

Determination of absolute configuration of secondary alcohols using new chiral auxiliary and chemical shift calculation

A new chiral carboxylic acid 1 was synthesized for determination of absolute configuration of secondary alcohols. Several chiral alcohols were converted to esters with 1. Their experimental esterification shift changes were successfully reproduced by the chemical shift simulation method combined with molecular dynamic simulation.     

Computation of the reduction free energy of coenzyme in aqueous solution by the QM/MM-ER method

In a recent development we proposed a quantum chemical approach to compute free energy change for chemical reactions in condensed phases by combining the QM/MM method with the theory of energy representation (QM/MM-ER). We extend in this Letter the novel approach to compute reduction free energy of isoalloxazine ring of FAD (flavin adenine dinucleotide) immersed in water within the framework of the QM/MM-ER method. The characteristic feature of our approach is that the excess electron to be attached on the FAD is identified as a solute. The reduction free energy has been obtained as −80.1 kcal/mol in the aqueous solution.     

Construction of a pH-responsive artificial membrane fusion system by using designed coiled-coil polypeptides

In many viruses, pH-responsive coiled-coil domains in the specific fusion proteins play important roles in membrane fusion and the infection of viruses into host cells. To investigate the relationship between the conformational change of the coiled coil and the fusion process, we have introduced a de novo designed polypeptide as a model system of the coiled-coil domain. This system enables the systematic study of the dynamics of pH-responsive coiled-coil polypeptide-membrane interactions. First, we designed and synthesized pH-responsive isoleucine-zipper triple-stranded coiled-coil polypeptides. Then the relationship between the pH-induced conformational change of the polypeptide and the membrane's interactive properties was studied by physicochemical methods. Structural changes in the designed polypeptides were examined by means of circular dichroism measurements. And finally, the behavior of the membrane fusion was investigated by leakage of liposomal contents, turbidity analysis, dynamic light scattering, and lipid mixing experiments. Our data show that coiled-coil formation under acidic pH conditions enhances polypeptide-induced membrane fusion. The results in this study demonstrate that an artificial membrane fusion system can be constructed on a molecular level by the use of a pH-responsive isoleucine-zipper triple-stranded coiled-coil polypeptide.     

Photoelectrochemistry of p-type Cu2O semiconductor electrode in ionic liquid

We investigated the photoelectrochemical characteristics and photo-stability of Cu₂O layered on a copper plate using a hydrophobic ionic liquid. Our findings revealed that Cu₂O is stable under white light irradiation, provided water is removed from the electrolyte. Methyl viologen derivative, a well-established electron acceptor, was introduced to the ionic liquid electrolyte, allowing the photo-induced electron transfer reaction at the Cu₂O/electrolyte interface to be characterized. The methyl viologen derivative exhibited two distinct redox reactions at −0.56 V and −0.98 V vs. Ag/AgCl, clearly indicating that no dimer formation or co-proportionation reaction occurred. The excessive photocurrents being continuously generated resulted from a viable photo-induced electron transfer reaction from the Cu₂O to the acceptor. However, in contrast, the reduction of the Cu₂O by water in the aqueous solution causes this electron transfer to be inhibited. We further demonstrate that these findings are vital to understanding the role of the Cu₂O and its photoelectrochemical applications.     

Activating an enzyme by an engineered coiled coil switch

We designed a de novo protein based on a circular permutant of RNaseT1, in which the enzymatic activity can be manipulated by engineered peptide binding. The circular permutant of RNaseT1 was obtained by tethering the original C- and N-termini with a GPAG linker and cleaving the molecule between Glu82 and Asn83. This mutant lacked enzymatic activity, due to the destabilization of entire protein structure. We previously reported the construction of ABC-type heterotrimeric coiled coil peptides, in which the A- and B-type peptides cannot form the folded trimeric structure without the C-type peptide. The introduction of the A- and B-type coiled coil peptides to the C- and N-termini of the circular permutant of RNaseT1, respectively, and the subsequent addition of the C-type coiled coil peptide enabled the RNaseT1 domain to refold properly, thus, restoring the enzymatic activity. The formation of the trimeric coiled coil structure should bring the cleaved sites of RNaseT1 close enough to refold the RNaseT1 domain spontaneously.