Molecular Iodine as a Catalyst for Alkene Difluorination.

The difluorination reaction of alkenes catalyzed by molecular iodine was revealed for the first time. This difluorination reaction affords a simple and practical experimental method and can be applied to many aliphatic and aromatic alkenes bearing synthetically useful functional groups, such as ester, amide, hydroxy, and aryl groups. Preliminary mechanistic studies of this alkene difluorination suggest the existence of two catalytic cycles: the IF-driven cycle and the catalytic cycle by the IF adduct.

The Effect of Torsional Motion on Multiexciton Formation through Intramolecular Singlet Fission in Ferrocene-Bridged Pentacene Dimers.

A series of ferrocene(Fc)-bridged pentacene(Pc)-dimers [Fc-Ph(2,n)-(Pc)2 : n=number of phenylene spacers] were synthesized to examine the tortional motion effect of Fc-terminated phenylene linkers on strongly coupled quintet multiexciton (5 TT) formation through intramolecular singlet fission (ISF). Fc-Ph(2,4)-(Pc)2 has a relatively small electronic coupling and large conformational flexibility according to spectroscopic and theoretical analyses. Fc-Ph(2,4)-(Pc)2 exhibits a high-yield 5 TT together with quantitative singlet TT (1 TT) generation through ISF. This demonstrates a much more efficient ISF than those of other less flexible Pc dimers. The activation entropy in 1 TT spin conversion of Fc-Ph(2,4)-(Pc)2 is larger than those of the other systems due to the larger conformational flexibility associated with the torsional motion of the linkers. The torsional motion of linkers in 1 TT is attributable to weakened metal-ligand bonding in the Fc due to hybridization of the hole level of Pc to Fc in 1 TT unpaired orbitals.

An emissive charge-transfer excited-state at the well-defined hetero-nanostructure interface of an organic conjugated molecule and two-dimensional inorganic nanosheet.

Precise engineering of excited-state interactions between an organic conjugated molecule and a two-dimensional semiconducting inorganic nanosheet, specifically the manipulation of charge-transfer excited (CTE) states, still remains a challenge for state-of-the-art photochemistry. Herein, we report a long-lived, highly emissive CTE state at structurally well-defined hetero-nanostructure interfaces of photoactive pyrene and two-dimensional MoS2 nanosheets via an N-benzylsuccinimide bridge (Py-Bn-MoS2). Spectroscopic measurements reveal that no charge-transfer state is formed in the ground state, but the locally-excited (LE) state of pyrene in Py-Bn-MoS2 efficiently generates an unusual emissive CTE state. Theoretical studies elucidate the interaction of MoS2 vacant orbitals with the pyrene LE state to form a CTE state that shows a distinct solvent dependence of the emission energy. This is the first example of organic-inorganic 2D hetero-nanostructures displaying mixed luminescence properties by an accurate design of the bridge structure, and therefore represents an important step in their applications for energy conversion and optoelectronic devices and sensors.

Biomimetic design of an α-ketoacylphosphonium-based light-activated oxygenation auxiliary.

The biomimetic design of a transition metal complex based on the iron(iv)-oxo porphyrin π-cation radical species in cytochrome P450 enzymes has been studied extensively. Herein, we translate the functions of this iron(iv)-oxo porphyrin π-cation radical species to an α-ketoacyl phosphonium species comprised of non-metal atoms and utilize it as a light-activated oxygenation auxiliary for ortho-selective oxygenation of anilines. Visible light irradiation converts the α-ketoacyl phosphonium species to the excited state, which acts as a transiently generated oxidant. The intramolecular nature of the process ensures high regioselectivity and chemoselectivity. The auxiliary is easily removable. A one-pot protocol is also described.

Probing exciton dynamics with spectral selectivity through the use of quantum entangled photons.

Quantum light is increasingly recognized as a promising resource for developing optical measurement techniques. Particular attention has been paid to enhancing the precision of the measurements beyond classical techniques by using nonclassical correlations between quantum entangled photons. Recent advances in the quantum optics technology have made it possible to manipulate spectral and temporal properties of entangled photons, and photon correlations can facilitate the extraction of matter information with relatively simple optical systems compared to conventional schemes. In these respects, the applications of entangled photons to time-resolved spectroscopy can open new avenues for unambiguously extracting information on dynamical processes in complex molecular and materials systems. Here, we propose time-resolved spectroscopy in which specific signal contributions are selectively enhanced by harnessing nonclassical correlations of entangled photons. The entanglement time characterizes the mutual delay between an entangled twin and determines the spectral distribution of photon correlations. The entanglement time plays a dual role as the knob for controlling the accessible time region of dynamical processes and the degrees of spectral selectivity. In this sense, the role of the entanglement time is substantially equivalent to the temporal width of the classical laser pulse. The results demonstrate that the application of quantum entangled photons to time-resolved spectroscopy leads to monitoring dynamical processes in complex molecular and materials systems by selectively extracting desired signal contributions from congested spectra. We anticipate that more elaborately engineered photon states would broaden the availability of quantum light spectroscopy.

Myocardial fat accumulation is associated with cardiac dysfunction in patients with type 2 diabetes, especially in elderly or female patients: a retrospective observational study.

BACKGROUND: Ectopic fat is fat that accumulates in or around specific organs or compartments of the body including myocardium. The clinical features of type 2 diabetes patients with high fat accumulation in the myocardium remain unknown. Moreover, little is known about the influence of myocardial fat accumulation in type 2 diabetes on coronary artery disease and cardiac dysfunction. We aimed to clarify the clinical features, including cardiac functions, of type 2 diabetes patients with myocardial fat accumulation. METHODS: We retrospectively enrolled type 2 diabetes patients who underwent ECG-gated coronary computed tomography angiography (CCTA) and abdominal computed tomography (CT) scan examinations within 1 year of CCTA from January 2000 to March 2021. High fat accumulation in the myocardium was defined as the low mean myocardial CT value of three regions of interest, and the associations between CT values and clinical characteristics or cardiac functions were assessed. RESULTS: In total, 124 patients were enrolled (72 males and 52 females). The mean age was 66.6 years, the mean BMI was 26.2 kg/m2, the mean ejection fraction (EF) was 67.6%, and the mean myocardial CT value was 47.7 Hounsfield unit. A significant positive correlation was found between myocardial CT value and EF (r = 0.3644, p = 0.0004). The multiple regression analyses also showed that myocardial CT value was independently associated with EF (estimate, 0.304; 95% confidence interval (CI) 0.092 to 0.517; p = 0.0056). Myocardial CT value showed significant negative correlations with BMI, visceral fat area and subcutaneous fat area (r = - 0.1923, - 0.2654, and -0.3569, respectively, p < 0.05). In patients who were ≥ 65 years or female, myocardial CT value showed significant positive correlations with not only EF (r = 0.3542 and 0.4085, respectively, p < 0.01) but also early lateral annular tissue Doppler velocity (Lat e') (r = 0.5148 and 0.5361, respectively, p < 0.05). The multiple regression analyses showed that myocardial CT value was independently associated with EF and Lat e' in these subgroups (p < 0.05). CONCLUSIONS: Patients with type 2 diabetes, especially in elderly or female patients, who had more myocardial fat had more severe left ventricular systolic and diastolic dysfunctions. Reducing myocardial fat accumulation may be a therapeutic target for type 2 diabetes patients.

Raman Spectroscopic and DFT Study of COA-Cl and Its Analogues.

COA-Cl is a newly synthesized adenosine analogue that exhibits various physiological activities. Its angiogenic, neurotropic, and neuroprotective potencies make it promising for the development of medicines. In this study, we show Raman spectroscopic study of COA-Cl to elucidate molecular vibrations and related chemical properties. Density functional theory calculations were combined with the Raman spectroscopic data to understand the details of each vibrational mode. Comparative analysis with adenine, adenosine, and other nucleic acid analogues enabled identification of unique Raman peaks originating from the cyclobutane moiety and chloro group of COA-Cl. This study provides fundamental knowledge and crucial insights for further development of COA-Cl and related chemical species.

A Catalytic Alkylation of Ketones via sp3 C-H Bond Activation.

We identified a ternary hybrid catalyst system composed of an acridinium photoredox catalyst, a thiophosphoric imide (TPI) catalyst, and a titanium complex catalyst that promoted an intermolecular addition reaction of organic molecules with various ketones through sp3 C-H bond activation. The thiyl radical generated via single-electron oxidation of TPI by the excited photoredox catalyst abstracted a hydrogen atom from organic molecules such as toluene, benzyl alcohol, alkenes, aldehydes, and THF. The thus-generated carbon-centered radical species underwent addition to ketones and aldehydes. This intrinsically unfavorable step was promoted by single-electron reduction of the intermediate alkoxy radical by catalytically generated titanium(III) species. This reaction provided an efficient and straightforward route to a broad range of tertiary alcohols and was successfully applied to late-stage functionalization of drugs or their derivatives. The proposed mechanism was supported by both experimental and theoretical studies.

Reference interaction site model self-consistent field with constrained spatial electron density approach for nuclear magnetic shielding in solution.

We propose a new hybrid approach combining quantum chemistry and statistical mechanics of liquids for calculating the nuclear magnetic resonance (NMR) chemical shifts of solvated molecules. Based on the reference interaction site model self-consistent field with constrained spatial electron density distribution (RISM-SCF-cSED) method, the electronic structure of molecules in solution is obtained, and the expression for the nuclear magnetic shielding tensor is derived as the second-order derivative of the Helmholtz energy of the solution system. We implemented a method for calculating chemical shifts and applied it to an adenine molecule in water, where hydrogen bonding plays a crucial role in electronic and solvation structures. We also performed the calculations of 17O chemical shifts, which showed remarkable solvent dependence. While converged results could not be sometimes obtained using the conventional method, in the present framework with RISM-SCF-cSED, an adequate representation of electron density is guaranteed, making it possible to obtain an NMR shielding constant stably. This introduction of cSED is key to extending the method's applicability to obtain the chemical shift of various chemical species. The present demonstration illustrates our approach's superiority in terms of numerical robustness and accuracy.

Semi-quantitative evaluation of chest computed tomography for coronavirus disease 2019 in a critical care unit: A case-control study.

The spread of abnormal opacity on chest computed tomography (CT) has been reported as a predictor of coronavirus disease 2019 (COVID-19) severity; however, the relationship between CT findings and prognosis in patients with severe COVID-19 remains unclear. The objective of this study was to evaluate the extent of abnormal opacity on chest CT and its association with prognosis in patients with COVID-19 in a critical care medical center, using a simple semi-quantitative method. This single-center case-control study included patients diagnosed with severe COVID-19 pneumonia who were admitted to a critical care center. The diagnosis of COVID-19 was based on positive results of a reverse transcription polymerase chain reaction test. All patients underwent non-contrast whole-body CT upon admission. Six representative axial chest CT images were selected for each patient to evaluate the extent of lung lesions. The percentage of the area involved in the representative CT images was visually assessed by 2 radiologists and scored on 4-point scale to obtain the bedside CT score, which was compared between patients who survived and those who died using the Mann-Whitney U test. A total of 63 patients were included in this study: 51 survived and 12 died after intensive treatment. The inter-rater reliability of bedside scores between the 2 radiologists was acceptable. The median bedside CT score of the survival group was 12.5 and that of the mortality group was 16.5; the difference between the 2 groups was statistically significant. The degree of opacity can be easily scored using representative CT images in patients with severe COVID-19 pneumonia, without sophisticated software. A greater extent of abnormal opacity is associated with poorer prognosis. Predicting the prognosis of patients with severe COVID-19 could facilitate prompt and appropriate treatment.

Electron in a cube: Synthesis and characterization of perfluorocubane as an electron acceptor.

Fluorinated analogs of polyhedral hydrocarbons have been predicted to localize an electron within their cages upon reduction. Here, we report the synthesis and characterization of perfluorocubane, a stable polyhedral fluorocarbon. The key to the successful synthesis was the efficient introduction of multiple fluorine atoms to cubane by liquid-phase reaction with fluorine gas. The solid-state structure of perfluorocubane was confirmed using x-ray crystallography, and its electron-accepting character was corroborated electrochemically and spectroscopically. The radical anion of perfluorocubane was examined by matrix-isolation electron spin resonance spectroscopy, which revealed that the unpaired electron accepted by perfluorocubane is located predominantly inside the cage.

Extraction of local spin-coupled states by second quantized operators.

We present a methodology for analyzing chemical bonds embedded in the electronic wave function of molecules, especially in terms of spin correlations or so-called "local spin." In this paper, based on biorthogonal second quantization, the spin correlation functions of molecules are naturally introduced, which enables us to extract local singlet and local triplet elements from the wave function. We also clarify the relationship between these spin correlations and traditional chemical concepts, i.e., resonance structures. Several chemical reactions, including the intramolecular radical cyclization and the formation of preoxetane, are demonstrated to verify the analysis method numerically.

Solvation in nitration of benzene and the valence electronic structure of the Wheland intermediate.

Nitration of benzene is a representative aromatic substitution reaction related to the σ-complex (arenium ion or "Wheland" intermediate) concept. This reaction is typically carried out in a mixed acid solution to generate nitronium ions, and how solvent molecules play roles in the reaction has been of great interest. Here we will shed new light on the reaction, namely the electronic structure and the microscopic insights of the solvation, which have been rarely discussed so far. We studied this process using the reference interaction site model-self consistent field with constrained spatial electron density distribution (RISM-SCF-cSED) method, considering sulfuric acid or water molecules as a solvent. In this method, the electronic structure of the solute and the solvation structure are self-consistently determined based on quantum chemistry and statistical mechanics of molecular liquids. The solvation free energy surfaces in solution and solvation structures were verified. In the bond formation process of benzene and nitronium ions, the solvation structure by sulfuric acid molecules drastically changes and the solvation effect on the free energy is quite large. We revealed largely contributing resonance structures in the π-electron system of the σ-complex in gas and solution phases by analysing the valence electronic structures.

Excited states of chlorophyll a and b in solution by time-dependent density functional theory.

The ground state and excited state electronic properties of chlorophyll (Chl) a and Chl b in diethyl ether, acetone, and ethanol solutions are investigated using quantum mechanical and molecular mechanical calculations with density functional theory (DFT) and time-dependent DFT (TDDFT). Although the DFT/TDDFT methods are widely used, the electronic structures of molecules, especially large molecules, calculated with these methods are known to be strongly dependent on the functionals and the parameters used in the functionals. Here, we optimize the range-separated parameter, µ, of the CAM-B3LYP functional of Chl a and Chl b to reproduce the experimental excitation energy differences of these Chl molecules in solution. The optimal values of µ for Chl a and Chl b are smaller than the default value of µ and that for bacteriochlorophyll a, indicating the change in the electronic distribution, i.e., an increase in electron delocalization, within the molecule. We find that the electronic distribution of Chl b with an extra formyl group is different from that of Chl a. We also find that the polarity of the solution and hydrogen bond cause the decrease in the excitation energies and the increase in the widths of excitation energy distributions of Chl a and Chl b. The present results are expected to be useful for understanding the electronic properties of each pigment molecule in a local heterogeneous environment, which will play an important role in the excitation energy transfer in light-harvesting complex II.

Chemical Shift of Solvated Hydride Ion: Comparative Study with Solvated Fluoride Ion.

The NMR chemical shifts of hydride and fluoride ions in the solution phase are evaluated from the first principle. The cluster structure in the first solvation shell is calculated by density functional theory and MP2 theory, and the solvent effect around the cluster is considered by PCM and RISM-SCF-SEDD methods. The obtained shifts are analyzed in terms of electronic structure and solvent effects and are compared with available experimental data. The fluoride ion is deshielded in the presence of solvent molecules compared to the isolated state due to a larger paramagnetic contribution from the 2p orbital. On the other hand, there is no such change for the hydride ion. The paramagnetic and diamagnetic contributions are slightly changed due to the solvation, but they are canceled out. As a result, the chemical shift of the hydride ion is less affected by the solvent than that of the fluoride ion. The increased diamagnetic contribution of hydride ion dissolved in the solvent is attributed to the change in electron density coupled with microscopic solvation.

Identification of a Self-Photosensitizing Hydrogen Atom Transfer Organocatalyst System.

We developed organocatalyst systems to promote the cleavage of stable C-H bonds, such as formyl, α-hydroxy, and benzylic C-H bonds, through a hydrogen atom transfer (HAT) process without the use of exogenous photosensitizers. An electronically tuned thiophosphoric acid, 7,7'-OMe-TPA, was assembled with substrate or co-catalyst N-heteroaromatics through hydrogen bonding and π-π interactions to form electron donor-acceptor (EDA) complexes. Photoirradiation of the EDA complex induced stepwise, sequential single-electron transfer (SET) processes to generate a HAT-active thiyl radical. The first SET was from the electron-rich naphthyl group of 7,7'-OMe-TPA to the protonated N-heteroaromatics and the second proton-coupled SET (PCET) from the thiophosphoric acid moiety of 7,7'-OMe-TPA to the resulting naphthyl radical cation. Spectroscopic studies and theoretical calculations characterized the stepwise SET process mediated by short-lived intermediates. This organocatalytic HAT system was applied to four different carbon-hydrogen (C-H) functionalization reactions, hydroxyalkylation and alkylation of N-heteroaromatics, acceptorless dehydrogenation of alcohols, and benzylation of imines, with high functional group tolerance.

Iodine-Mediated Fluorination of Alkenes with an HF Reagent: Regioselective Synthesis of 2-Fluoroalkyl Iodides.

Fluorination reaction of alkenes with iodine and HF·pyridine complex (pyr·9HF) was performed under mild conditions in the presence of K2S2O8 or Na2S2O8 as an oxidant. Aliphatic and aromatic alkenes underwent iodofluorination to give the iodofluorinated products with high regioselectivity. The substitution reactions of the iodofluorinated product by nitrogen, sulfur, and oxygen nucleophiles indicated further applications as a building block for synthesis of 2-fluoroalkyl-substituted compounds.

Theoretical study of the mechanism of the solvent dependency of ESIPT in HBT.

2-(2'-Hydroxyphenyl)-benzothiazole (HBT) has been widely studied for use as a system for excited-state intramolecular proton transfer. However, the mechanism underlying the solvent dependency of HBT fluorescence spectra remains unclear. In this study, the HBT photochemical process in the S1 state was analysed using density functional theory (DFT) and time-dependent density functional theory (TDDFT). The excited-state intramolecular proton transfer in the enol form of HBT was found to depend on the hydrogen-bond acceptability of the solvent. The twisting of the keto form of HBT is determined by whether HBT acts as a hydrogen-bond acceptor or donor. A specific stacking structure of the enol form of HBT was found to decrease the S1 → S0 transition energy, which corresponds to the experimental fluorescence spectra in a DMSO/H2O solution mixture.

Theoretical study on isomerization of α-acids: A DFT calculation.

The α-acids contained in hops are one of the ingredients of beer. The isomerization of α-acids produces iso-α-acids, the main source of bitterness in beer. In this study, the isomerization mechanism of the α-acid, cohumulone, was elucidated by using density functional theory in conjunction with the polarizable continuum model or 3D-RISM integral equation theory of liquids. The calculated reaction diagram is consistent with experimental results; the activation free energy difference between the cis and trans isomers is in good agreement with the experimental estimate. The activation energy difference results from solvation energy. Additionally, a calculation of NMR chemical shifts showed that the proton position of isocohumulone is different from that proposed previously. The effect of Mg2+ cation on the isomerization was also investigated. Both the activation and reaction free energy are stabilized by the presence of Mg2+, which is consistent with experimental results. Water solvation reduces the activation free energy.