Competing Excited‐State Hydrogen and Proton‐Transfer Processes in 6‐Azaindole‐S3,4 and 2,6‐Diazaindole‐S3,4 Clusters (S=H2O, NH3)

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Competing Excited-State Hydrogen and Proton-Transfer Processes in 6-Azaindole-S3,4 and 2,6-Diazaindole-S3,4 Clusters (S=H2O, NH3)

Excited-state hydrogen and proton transfer pathways (ESHT and ESPT, respectively) in 6-azaindole (6AI-S3,4) and 2,6-diazaindole (26DAI-S3,4)(S=H2O, NH3) were explored computationally. Lengthening the solvent chain and replacing the water molecule with ammonia decreased the energy barriers. The ESPT barriers are higher than the barriers in the ESHT process. The effect of N(2) insertion was explored for the first time in isolated solvent clusters for both ESHT and ESPT processes.


Abstract

Excited state hydrogen (ESHT) and proton (ESPT) transfer reaction pathways in the three and four solvent clusters of 6-azaindole (6AI-S3,4) and 2,6-diazaindole (26DAI-S3,4)(S=H2O, NH3) were computationally investigated to understand the fate of photo-excited biomolecules. The ESHT energy barriers in (H2O)3 complexes (39.6–41.3 kJmol−1) were decreased in (H2O)4 complexes (23.1–20.2 kJmol−1). Lengthening the solvent chain lowered the barrier because of the relaxed transition states geometries with reduced angular strains. Replacing the water molecule with ammonia drastically decreased the energy barriers to 21.4–21.3 kJmol−1 in (NH3)3 complexes and 8.1–9.5 kJ mol−1 in (NH3)4 complexes. The transition states were identified as Ha atom attached to the first solvent molecule. The formation of stronger hydrogen bonds in (NH3)3,4 complexes resulted in facile ESHT reaction than that in the (H2O)3,4 complexes. The ESPT energy barriers in 6AI-S3,4 and 26DAI-S3,4 were found to range between 40–73 kJmol−1. The above values were significantly higher than that of the ESHT processes and hence are considered as a minor channel in the process. The effect of N(2) insertion was explored for the very first time in the isolated solvent clusters using local vibrational mode analysis. In DAI-S4, the higher Ka(Ha⋯Sa) values depicted the increased photoacidity of the N(1)-Ha group which may facilitate the hydrogen transfer reaction. However, the increased N(6)⋯Hb bond length elevated the reaction barriers. Therefore, in the ESHT reaction channel, the co-existence of two competing factors led to a marginal/no change in the overall energy barriers due to the N(2) insertion. In the ESPT reaction pathway, the energy barriers showed notable increase upon N(2) insertion because of the increased N(6)⋯Hb bond length.

Electronic Properties of Transition and Alkaline Earth Metal Doped CuS: A DFT Study

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Electronic Properties of Transition and Alkaline Earth Metal Doped CuS: A DFT Study

Doping of CuS is shown through density functional theory calculations to allow control of the band gap and semiconductor behavior by changing the bond ionicity. Doping with Mg, Ca, and Zn may also enhance electron mobility and charge separation.


Abstract

CuS is a unique semiconductor with potential in optoelectronics. Its unusual electronic structure, including a partially occupied valence band, and complex crystal structure with an S−S bond offer unique opportunities and potential applications. In this work, the use of doping to optimize the properties of CuS for various applications is investigated by density functional theory (DFT) calculations. Among the dopants studied, Ni, Zn, and Mg may be the most practical due to their lower formation energies. Doping with Fe, Ni, or Ca induces significant distortion, which may be beneficial for achieving materials with high surface areas and active states. Significantly, doping alters the conductor-like behavior of CuS, opening a band gap by increasing bond ionicity and reducing the S−S bond covalency. Thus, doping CuS can tune the plasmonic properties and transform it from a conductor to an intrinsic fluorescent semiconductor. Ni and Fe doping give the lowest band gaps (0.35 eV and 0.39 eV, respectively), while Mg doping gives the highest (0.86 eV). Doping with Mg, Ca, and Zn may enhance electron mobility and charge separation. Most dopants increase the anisotropy of electron-to-hole mass ratios, enabling device design that exploits directional-dependence for improved performance.

Apoptotic activity of genipin in human oral squamous cell carcinoma in vitro by regulating STAT3 signaling

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Abstract

Genipin, a natural compound derived from the fruit of Gardenia jasminoides Ellis, was reported to have activity against various cancer types. In this study, we determined the underlying mechanism for genipin-induced cell death in human oral squamous cell carcinoma (OSCC). The growth-inhibitory effects of genipin in human OSCC cells was examined by the Cell Counting Kit-8 and soft agar assays. The effects of genipin on apoptosis were assessed by nuclear morphological changes by 4′,6-diamidino-2-phenylindole staining, measurement of the sub-G1 population, and Annexin V-fluorescein isothiocyanate/propidium iodide double staining. The underlying mechanism of genipin activity was analyzed by western blot analysis, subcellular fractionation of the nucleus and cytoplasm, immunocytochemistry, and quantitative real-time polymerase chain reaction. Genipin inhibited the growth of OSCC cells and induced apoptosis, which was mediated by a caspase-dependent pathway. Genipin reduced the phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr705 and its nuclear localization. Furthermore, inhibition of p-STAT3Tyr705 levels following genipin treatment was required for the reduction of survivin and myeloid cell leukemia-1 (Mcl-1) expression, leading to apoptotic cell death. The genipin-mediated reduction in survivin and Mcl-1 expression was caused by transcriptional and/or posttranslational regulatory mechanisms. The results provide insight into the regulatory mechanism by which genipin induces apoptotic cell death through the abrogation of nuclear STAT3 phosphorylation and suggest that genipin may represent a potential therapeutic option for the treatment of human OSCC.

Determination of the Handedness of Urea Inclusion Compounds

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Determination of the Handedness of Urea Inclusion Compounds

“We aimed to push the absolute configuration capacity of X-ray diffraction to its limit.” This and more about the story behind the front cover can be found in the article at 10.1002/chem.202302217).


Abstract

Invited for the cover of this issue is the group of Bo Wang at Biogen. The image depicts the sectored chiral domains of urea inclusion compounds. Read the full text of the article at 10.1002/chem.202302217.

HER‐2‐targeted Boron Neutron Capture Therapy with Carborane‐integrated Immunoliposomes Prepared via an Exchanging Reaction

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Boron neutron capture therapy (BNCT) is a promising modality for cancer treatment because of its minimal invasiveness. To maximize the therapeutic benefits of BNCT, the development of efficient platforms for the delivery of boron agents is indispensable. Here, we prepared carborane-integrated immunoliposomes via an exchanging reaction to achieve HER-2-targeted BNCT. The conjugation of an anti-HER-2 antibody to carborane-integrated liposomes successfully endowed these liposome with targeting properties toward HER-2-overexpressing human ovarian cancer cells (SK-OV3); the resulting BNCT activity toward SK-OV3 cells obtained using the current immunoliposomal system was 14-fold that of the l-BPA/fructose complex, which is a clinically available boron agent. Moreover, the growth of spheroids treated with our system followed by thermal neutron irradiation was significantly suppressed compared with treatment with the l-BPA/fructose complex.

Hydrogen bond energy estimation (H‐BEE) in large molecular clusters: A Python program for quantum chemical investigations

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Hydrogen bond energy estimation (H-BEE) in large molecular clusters: A Python program for quantum chemical investigations

This work reports the automated H-BEE code for estimating individual hydrogen bond energies and cooperativity contributions in molecular clusters using MTA-based method employing (i) the actual molecular cluster, (ii) the SS1 model, and (iii) the Frags-in-Frags method. This automated code overcomes the tedious manual fragmentation involved in the respective method.


Abstract

A procedure, derived from the fragmentation-based molecular tailoring approach (MTA), has been proposed and extensively applied by Deshmukh and Gadre for directly estimating the individual hydrogen bond (HB) energies and cooperativity contributions in molecular clusters. However, the manual fragmentation and high computational cost of correlated quantum chemical methods make the application of this method to large molecular clusters quite formidable. In this article, we report an in-house developed software for automated hydrogen bond energy estimation (H-BEE) in large molecular clusters. This user-friendly software is essentially written in Python and executed on a Linux platform with the Gaussian package at the backend. Two approximations to the MTA-based procedure, viz. the first spherical shell (SS1) and the Fragments-in-Fragments (Frags-in-Frags), enabling cost-effective, automated evaluation of HB energies and cooperativity contributions, are also implemented in this software. The software has been extensively tested on a variety of molecular clusters and is expected to be of immense use, especially in conjunction with correlated methods such as MP2, CCSD(T), and so forth.

Curcumin promotes apoptosis of human melanoma cells by caspase 3

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Abstract

Cutaneous melanoma (CM) is a malignant neoplasm with a high metastatic rate that shows poor response to systemic treatments in patients with advanced stages. Recently, studies have highlighted the antineoplastic potential of natural compounds, such as polyphenols, in the adjuvant therapy context to treat CM. The objective of the present study was to evaluate the effect of different concentrations of curcumin (0.1–100 µM) on the metastatic CM cell line SK-MEL-28. The cells were treated for 6 and 24 h with different concentrations of curcumin. Cell viability was assessed by 3-(4,5-dimethyl-2thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and fluorescence microscopy. The apoptotic-inducing potential was detected by annexin V flow cytometry. The wound healing assay was used to verify cell migration after the curcumin exposition. The redox profile was evaluated by levels of the pro-oxidant markers reactive oxygen species (ROS) and Nitric oxide (NOx) and antioxidants of total thiols (PSH) and nonprotein thiols. The gene expression and enzymatic activity of caspase 3 were evaluated by reverse transcription-quantitative polymerase chain reaction and a sensitive fluorescence assay, respectively. Curcumin significantly decreased the cell viability of SK-MEL-28 cells at both exposure times. It also induced apoptosis at the highest concentration tested (p < .0001). SK-MEL-28 cell migration was inhibited by curcumin after treatment with 10 µM (p < .0001) and 100 µM (p < .0001) for 6 and 24 h (p = .0006 and p < .0001, respectively). Furthermore, curcumin significantly increased levels of ROS and NOx. Finally, curcumin was capable of increasing the gene expression at 10 µM (p = .0344) and 100 µM (p = .0067) and enzymatic activity at 10 µM (p = .0086) and 100 µM (p < .0001) of caspase 3 after 24 h. For the first time, we elucidated in our study that curcumin increases ROS levels, promoting oxidative stress that activates the caspase pathway and culminates in SK-MEL-28 metastatic CM cell death.

Dual strategies with anion/cation co‐doping and lithium carbonate coating to enhance the electrochemical performance of Li‐rich layered oxides

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Lithium-rich layered oxides (LLOs, Li1.2Mn0.54Ni0.13Co0.13O2) are widely used as cathode materials for lithium-ion batteries due to its high specific capacity, high operating voltage and low cost. However, the LLOs are faced with rapid decay of charge/discharge capacity and voltage, as well as interface side reactions, which limit its electrochemical performance. Herein, the dual strategies of sulfite/sodium ion co-doping and lithium carbonate coating were used to improve it. It founds that modified LLOs achieve 88.74% initial coulomb efficiency, 295.3 mAh g–1 first turn discharge capacity, in addition to 216.9 mAh g–1 at 1 C, and 87.23% capacity retention after 100 cycles. Mechanism research indicated that the excellent electrochemical performance benefits from the doping of both Na+ and SO32-, and it could significantly reduce the migration energy barrier of Li+ and promote Li+ migration. Meanwhile, anion and cation are co-doped greatly reduces the band gap of LLOs and increase its electrical conductivity, and no electron spin barrier leap effect at the Fermi level. In addition, the lithium carbonate coating significantly inhibits the occurrence of interfacial side reactions of LLOs. This work provides a theoretical basis and practical guidance for the further development of LLOs with higher electrochemical performance.

Selection of highly specific DNA aptamer for the development of QCM‐based arsenic sensor

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Heavy metal arsenic is a water pollutant that affects millions of lives worldwide. A novel aptamer candidate for specific and sensitive arsenic detection was identified using Graphene Oxide-SELEX (GO-SELEX). Eleven rounds of GO-SELEX were performed to screen As(III) specific sequences. The selected aptamer sequences were evaluated for their binding affinity. The dissociation constant of the best aptamer candidate, As-06[1], was estimated by fluorescence recovery upon target addition, and it was found to be 8.15 nM. A QCM-based biosensing platform was designed based on the target-triggered release of aptamer from the QCM electrode. An rGO-SWCNT nanocomposite was adsorbed on the gold surface, and the single-stranded probe was stacked on the rGO-CNT layer. Upon addition of the target to the solution, a concentration-dependent release of the ssDNA probe was observed and recorded as the change in the electrode frequency. The developed QCM sensor showed a dynamic linear range from 10 nM to 100 nM and a low detection limit of 8.6 nM. The sensor exhibited excellent selectivity when challenged with common interfering anions and cations.       [1] The Provisional IN Patent Application No.: 202311048776, titled An arsenic-binding aptamer and method of preparing the same, filed on July 20, 2023.

Recent Advances in Chemical Synthesis of Structural Domains of Lipopolysaccharides from the Commensal Gut‐Associated Microbiota

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Recent Advances in Chemical Synthesis of Structural Domains of Lipopolysaccharides from the Commensal Gut-Associated Microbiota

Lipopolysaccharides from the commensal gut-associated microbiota are interesting biomolecules for the treatment of various inflammatory diseases. The recent synthesis of lipopolysaccharides from gut-associated lymphoid-tissue-resident Alcaligenes faecalis and Bacteroides vulgatus are highlighted.


Abstract

Lipopolysaccharides from the commensal gut-associated microbiota are interesting biomolecules for the treatment of various inflammatory diseases. Different from pathogenic lipopolysaccharides, commensal lipopolysaccharides have distinct chemical structures and mediate beneficial homeostasis with the immune system of the host. However, the accessibility issues of homogenous and pure commensal lipopolysaccharides hampered the in-depth studies of their functions. In this concept article, we highlight the recent synthesis of lipopolysaccharides from gut-associated lymphoid-tissue-resident Alcaligenes faecalis and Bacteroides vulgatus, which hopes to inspire the more efforts devoting to these fantastic biomolecules.