Histone deacetylase (HDAC) inhibitor curcumin upregulates mitochondrial uncoupling protein1 (UCP1) and mitochondrial function in brown adipocytes,in-silico study and screening natural drug library

Mitochondrial dysfunction has been associated with diverse pathological conditions globally. Specifically, in adipose tissues, mitochondrial dysfunction is the primary cause of obesity and obesity-related illnesses. An existing drugs such as atorvastatin and other lipid-lowering drugs demonstrated adverse effects and initiated other diseases. Thus, we need to explore new methods to prevent and treat obesity. In this study, we used the cell screening method to identify several natural compounds that increase adipocyte UCP1 gene expression. The identified drug Curcumin was evaluated in cell models and the In-silico model. We found curcumin is an active compound of turmeric belonging to Zingiberaceae (ginger family), which activates the Nrf2 mechanism. Curcumin potentially endorses the expression of UCP1 in the brown adipocyte in vitro cellular model. Curcumin plays an important role that modulating mitochondrial function and improving mitochondrial DNA quantification, ATP production, and cell viability. We have established an efficient in vitro cell experiment system to study the metabolic regulation of UCP1. The in-silico model revealed curcumin-UCP1 interaction. Curcumin, via enhancing mitochondrial activity, could be a helpful therapeutic molecule against metabolic disorders or obesity-related diseases. Curcumin will be the subject of more research in both human and murine models, which will provide novel therapeutic pathways for the treatment of metabolic illnesses by modulating the control of mitochondrial function.     

Photochemical Hydrogen Storage with Hexaazatrinaphthylene

When irradiated with violet light, hexaazatrinaphthylene (HATN) extracts a hydrogen atom from an alcohol forming a long-living hydrogenated species. The apparent kinetic isotope effect for fluorescence decay time in deuterated methanol (1.56) indicates that the lowest singlet excited state of the molecule is a precursor for intermolecular hydrogen transfer. The photochemical hydrogenation occurs in several alcohols (methanol, ethanol, isopropanol) but not in water. Hydrogenated HATN can be detected optically by an absorption band at 1.78 eV as well as with EPR (electron paramagnetic resonance) and NMR techniques. Mass spectrometry of photoproducts reveal di-hydrogenated HATN structures along with methoxylated and methylated HATN molecules which are generated through the reaction with methoxy radicals (remnants from alcohol splitting). Experimental findings are consistent with the theoretical results which predicted that for the excited state of the HATN-solvent molecular complex, there exists a barrierless hydrogen transfer from methanol but a small barrier for the similar oxidation of water.     

A DFT Study on the Binuclear Copper(I)-Catalyzed Synthesis Mechanism of 1,2,3-Triazolo[1,5-c]Pyrimidine via Interrupted Click and Ketenimine Rearrangement

In this paper, the mechanism of the full catalytic cycle for binuclear Cu(I)-catalyzed sulfonyl azide-alkyne cycloaddition reaction for the synthesis of triazolopyrimidines was rationalized by density functional theoretical (DFT) calculations. The computed reaction route consists of: (a) formation of dicopper intermediates, including C−H activation of terminal alkyne, 3+2 ring cycloaddition and ring-reducing reaction and transmetalation, (b) interrupted CuAAC reaction, including di-copper catalyzed ring-opening of 2H-azirines and C−C bond formation to generate the copper-triazoles and -ketenimines, (c) two-step C−N cross-coupling and following (d) multi-step hydrogen transfer by the hydrogen bonding chain of water to promote the C−N formation and another C−N cleavage through the removal of p-tolyl sulfonamides. Our DFT results indicate that the multi-step hydrogen transfer process is the rate-determining step along the potential energy surface profile. The explicit water model was used for systematic determination of barrier for C−C cross-coupling, C−N bond formation and cleavage, and p-tolylsulfonamide removal. A critical insight in the interrupted CuAAC reaction was proposed. Further prediction interprets H₂O hydrogen bond chain plays an important role in C−N bond formation and cleavage, and the removal of p-tolylsulfonamide. This may have fundamental guidance on the design of 1, 5-herterocyclic functionalized triazolopyrimidines via interrupted CuAAC rearrangement reaction, as well as hydrogen bond chain of water.     

Mixed Quantum Classical Reaction Rates based on the Phase Space Formulation of the Hierarchical Equations of Motion

In a previous work [J. Chem. Phys. 140 , 174105 (2014)], we have shown that a mixed quantum classical (MQC) rate theory can be derived to investigate the quantum tunneling effects in the proton transfer reactions. However, the method is based on the high temperature approximation of the hierarchical equation of motion (HEOM) with the Debye-Drude spectral density, and results in a multi-state Zusman type of equation. We now extend this theory to include quantum effects of the bath degrees of freedom. By writing the full HEOM into a multidimensional partial differential equation in phase space, we can define a new reaction coordinate, and the previous method can be generalized to the full quantum regime. The validity of the new method is demonstrated by using numerical examples, including the spin-Boson model, and the double well model for proton transfer reaction. The new method is found to resolve some key problems of the previous theory based on high temperature approximation, including possible numerical instability in long time simulation and wrong rate constant at low temperatures.     

Generalized Fourth-Order Decompositions of Imaginary Time Path Integral: Implications of the Harmonic Oscillator

The imaginary time path integral formalism offers a powerful numerical tool for simulating thermodynamic properties of realistic systems. We show that, when second-order and fourth-order decompositions are employed, they share a remarkable unified analytic form for the partition function of the harmonic oscillator. We are then able to obtain the expression of the thermodynamic property and the leading error terms as well. In order to obtain reasonably optimal values of the free parameters in the generalized symmetric fourth-order decomposition scheme, we eliminate the leading error terms to achieve the accuracy of desired order for the thermodynamic property of the harmonic system. Such a strategy leads to an efficient fourth-order decomposition that produces third-order accurate thermodynamic properties for general systems.     

Effects of Coverage,Water, and Defects on Catechol/TiO2 Interface

Catechol adsorbed on TiO₂ is one of the simplest models to explore the relevant properties of dye-sensitized solar cells. However, the effects of water and defects on the electronic levels and the excitonic properties of the catechol/TiO₂ interface have been rarely explored. Here, we investigate four catechol/TiO₂ interfaces aiming to study the influence of coverage, water, and defects on the electronic levels and the excitonic properties of the catechol/TiO₂ interface through the first-principles many-body Green's function theory. We find that the adsorption of catechol on the rutile (110) surface increases the energies of both the TiO₂ valence band maximum and conduction band minimum by approximately 0.7 eV. The increasing coverage and the presence of water can reduce the optical absorption of charge-transfer excitons with maximum oscillator strength. Regarding the reduced hydroxylated TiO₂ substrate, the conduction band minimum decreases greatly, resulting in a sub-bandgap of 2.51 eV. The exciton distributions in the four investigated interfaces can spread across several unit cells, especially for the hydroxylated TiO₂ substrate. Although the hydroxylated TiO₂ substrate leads to a lower open-circuit voltage, it may increase the separation between photogenerated electrons and holes and may therefore be beneficial for improving the photovoltaic efficiency by controlling its concentration. Our results may provide guidance for the design of highly efficient solar cells in future.     

Utilization of photocatalysts in decarboxylative coupling of carboxylic N-hydroxyphthalimide (NHPI) esters

Recently, the visible-light photoredox decarboxylative couplings of N-(acyloxy)phthalimides (NHPI esters) and its derivatives have become an efficient chemical transformation. Under visible light, the NHPI esters undergo a single-electron transfer (SET) process to afford the corresponding carbon or nitrogen radicals that participate in many chemical transformations. The photoredox decarboxylative couplings have been applied to achieve construction of an array of carbon–carbon and carbon–heteroatom bonds as well as the synthesis of carbocycles and heterocycles. This review categorises photocatalysts, discusses the application and catalysis mechanisms of NHPI esters, and details recent progress in this field.     

Recent advances in electrochemistry of pyridinium-based electrophores: A structronic approach

The context of molecular structronics (from “molecular structure” and “electronics”) is that of molecular-level electrochemical storage of energy of sustainable origin (wind, solar). Due to its discontinuous availability, storage of this energy is a key issue. The targeted type of storage relies on implementing “electron reservoirs” within the structronic molecules by electrochemically forming dedicated chemical bonds according to non-catalytic processes. Reservoir bonds are therefore integral parts of the molecular backbone of structronic assemblies. When filled, electron reservoirs manifest themselves in the form of elongated covalent bonds that are to be cleaved for electron releasing (discharging) on demand. The scope of this short review is limited to pyridinium electrophores as particularly suited building blocks for the development of structronics.     

The first representative of a new class of charge transfer complexes in o-quinone series for organic semiconductors

The first representative of a new class of charge transfer complexes for organic semiconductors was synthesized. The reaction of p-nitroaniline (PNA) with [1,10]-phenanthroline-5,6-dione (PD) results in the formation of a stable molecular charge transfer (CT) complex PNA₃-PD₂ in a ratio of 3:2. The structure of the molecular CT complex PNA₃-PD₂ was established by X-ray diffraction studies. Using the density functional theory method, it is shown that several types of intermolecular interactions are realized in the complex: between the PNA amino group and the nitro group of another PNA molecule, carbonyl groups, and PD nitrogen atoms. Complex PNA₃-PD₂ is stable only in solid form. The diffuse reflectance UV–vis spectrum of PNA₃-PD₂ crystal powder is characterized by the intense weakly structured long-wavelength absorption band up to 650 nm. Quantum chemical calculations of the electronic structure have shown that the complex PNA₃-PD₂ is a straight-band semiconductor with a band gap of 2.11 eV.     

Functional Group Modification and Bonding Characteristics of Ti3C2 MXene-Organic Composites from First-Principles Calculations

The unique physical structure and abundant surface functional groups of MXene make the grafted organic molecules exhibit specific electrical and optical properties. This work reports the results of first-principles calculations to investigate the composite systems formed by different organic molecular monomers, namely acrylic acid (AA), acrylamide (AM), 1-aziridineethanol (1-AD) and glucose, and Ti₃C₂ MXene saturated with different functional groups, namely −OH, −O and −F. The results show that the interaction between organic molecules and the MXene surface depends on the type of functional groups of the organic molecules, while the strength of the interaction is determined by the type of surface functional groups and the number of hydrogen bonds. The bare Ti₃C₂ and Ti₃C₂(OH)₂ can readily form strong chemical and hydrogen bonds with AA and AM molecules, leading to strong adsorption energy and a large amount of charge transfer, while the interaction between organic molecules and MXene saturated by −F or −O groups mainly exhibits physical interactions, accompanied by low adsorption energy and a small amount of charge transfer. This research provides theoretical guidance for the synthesis of high-performance MXene organic composite systems.