Exploring the Synthetic Application of Allylic Alcohol Isomerization

Allylic alcohol transposition lacks a thermodynamic driving force and usually displays stereo-infidelity and poor regioselectivity. However, regio- and stereoselectivity can be achived by coupling allylic alcohol transposition to a subsequent step that is kinetically and thermodynamically favorable. Based on this rationale, the allylic alcohol transposition and capture sequence was delevoped and applied successfully in heterocycle synthesis. Regio- and stereoselectivity were achieved when a pre-existing stereogenic center in the substrates could induce significant thermodynamic difference between diastereomeric products and when the individual steps toward these diastereomeric products were reversible. Epoxides were later used as ennantioenriched electrophiles in this transposition/trapping sequence for stereoselective synthesis of heterocycles. The mechanism for this transformation was elucidated and a cascade approach using epoxides as trapping agents in the transposition of allylic alcohols was developed and applied in the stereoselective formation of polycyclic ethers. Finally, an improved sequence using “traceless trapping agents” was developed. This new method did not leave any vestige in the resulting product and offered much more freedom for the application of allylic alcohol transposition in heterocycle synthesis. Understanding the relative rates of the steps in this new sequence led to the design of reactions that created multiple stereogenic centers with good to excellent levels of control

Diarylmethane synthesis through Re_2O_7-catalyzed bimolecular dehydrative Friedel–Crafts reactions

This manuscript describes the application of Re_2O_7 to the syntheses of diarylmethanes from benzylic alcohols through solvolysis followed by Friedel–Crafts alkylation. The reactions are characterized by broad substrate scope, low catalyst loadings, high chemical yields, and minimal waste generation. The intermediate perrhenate esters are superior leaving groups to chlorides and bromides in these reactions. The polarity and water sequestering capacity of hexafluoroisopropyl alcohol are critical to the success of these processes. Re_2O_7 is a precatalyst for HOReO_3, which serves as a less costly and easily handled promoter for these reactions. Oxorhenium catalysts selectively activate alcohols in the presence of similarly substituted acetates, indicating a unique chemoselectivity and mechanism in comparison to Brønsted acid catalysis

DrugChat: Towards Enabling ChatGPT-Like Capabilities on Drug Molecule Graphs

A ChatGPT-like system for drug compounds could be a game-changer in pharmaceutical research, accelerating drug discovery, enhancing our understanding of structure-activity relationships, guiding lead optimization, aiding drug repurposing, reducing the failure rate, and streamlining clinical trials. In this work, we make an initial attempt towards enabling ChatGPT-like capabilities on drug molecule graphs, by developing a prototype system DrugChat. DrugChat works in a similar way as ChatGPT. Users upload a compound molecule graph and ask various questions about this compound. DrugChat will answer these questions in a multi-turn, interactive manner. The DrugChat system consists of a graph neural network (GNN), a large language model (LLM), and an adaptor. The GNN takes a compound molecule graph as input and learns a representation for this graph. The adaptor transforms the graph representation produced by the GNN into another representation that is acceptable to the LLM. The LLM takes the compound representation transformed by the adaptor and users' questions about this compound as inputs and generates answers. All these components are trained end-to-end. To train DrugChat, we collected instruction tuning datasets which contain 10,834 drug compounds and 143,517 question-answer pairs. The code and data is available at \url{https://github.com/UCSD-AI4H/drugchat

Isomer-Dependent Adsorption and Release of Cis- and Trans-platin Anticancer Drugs by Mesopomus Silica Nanoparticles

We report on adsorption and release of the anticancer drugs cisplatin and transplatin from mesoporous silica nanomaterials, emphasizing the differences between cisplatin and its much less toxic isomer. Two types of particles, M.CM-41 and SBA-IS, were used, either as just synthesized or after calcination to remove the templates. The particles were characterized by TEM, nitrogen physisorption, and elemental analysis. The UV-vis spectra of cisplatin and transplatin were obtained and the intensities of several bands (205-210 nm, 210-220 nm, 220-235 nm, and 300-330 nm) were found proportional to drug concentrations, allowing their use for measuring drug concentration. To evaluate drug adsorption by nanoparticles, nanoparticles were incubated in drug solutions and removed by centrifugation, after which the supernatants were scanned by spectrometer to determine drug remaining. It was found that calcined MCM adsorbed less cisplatin or transplatin per particle than as-synthesized MCM. SBA nanoparticles adsorbed slightly more cisplatin than MCM, and slightly less transplatin. Measurements of drug adsorption as a function, of time show that drug is rapidly adsorbed by all particles studied. This rapid adsorption is probably associated with adsorption of drug on the external surfaces of the particles as well as the possible physisorption within the surfactant assemblies or by replacing the surfactant molecules or ions in the case of the assynthesized materials. For calcined SBA particles, it is followed by a slow take-up of drug, perhaps due to the internal pores. There is no slow take-up by as-synthesized SBA particles or by either as-synthesized or calcined MCM. particles. Measurement of the release of platinum drugs from, nanoparticles previously soaked in drug solutions showed a substantial quick release for all particles and both drugs. This was followed by a slow release of Pt species in the case of transplatin in calcined SBA

Diarylmethane synthesis through Re_2O_7-catalyzed bimolecular dehydrative Friedel–Crafts reactions

This manuscript describes the application of Re_2O_7 to the syntheses of diarylmethanes from benzylic alcohols through solvolysis followed by Friedel–Crafts alkylation. The reactions are characterized by broad substrate scope, low catalyst loadings, high chemical yields, and minimal waste generation. The intermediate perrhenate esters are superior leaving groups to chlorides and bromides in these reactions. The polarity and water sequestering capacity of hexafluoroisopropyl alcohol are critical to the success of these processes. Re_2O_7 is a precatalyst for HOReO_3, which serves as a less costly and easily handled promoter for these reactions. Oxorhenium catalysts selectively activate alcohols in the presence of similarly substituted acetates, indicating a unique chemoselectivity and mechanism in comparison to Brønsted acid catalysis

PLOD1 contributes to proliferation and glycolysis in hepatocellular carcinoma by regulating E2F1

Purpose: To evaluate the effect of procollagen-lysine 1,2-oxoglutarate 5-dioxygenase 1 (PLOD1) in hepatocellular carcinoma (HCC). Methods: HCC cells were subjected to loss of function assays via transfection with siRNA targeting PLOD1. Colony formation and cell counting kit 8 (CCK8) were used to determine cell proliferation. Cell cycle was evaluated by flow cytometry while extracellular acidification rate (ECAR) levels, glucose consumption, and lactate production were determined to investigate aerobic glycolysis. Results: PLOD1 was significantly up-regulated in HCC tissues and cells compared to normal tissues and cells (p < 0.001). Silencing of PLOD1 significantly repressed cell proliferation (p < 0.001) and induced cell cycle arrest in HCC at the G1 phase. ECAR levels, glucose consumption, and lactate production in HCC were reduced by knockdown of PLOD1. Loss of PLOD1 down-regulated the expression of E2F1, while over-expression of E2F1 attenuated PLOD1 knockdown-induced decreases in cell viability, glucose consumption, and lactate production in HCC. Conclusion: Knockdown of PLOD1 inhibits cell proliferation and aerobic glycolysis in HCC via down-regulation of E2F1. Thus, PLOD1 may help in developing an effective strategy for the management of liver cancer

Construction and experimental validation of a signature for predicting prognosis and immune infiltration analysis of glioma based on disulfidptosis-related lncRNAs

BackgroundsDisulfidptosis, a newly discovered mechanism of programmed cell death, is believed to have a unique role in elucidating cancer progression and guiding cancer therapy strategies. However, no studies have yet explored this mechanism in glioma.MethodsWe downloaded data on glioma patients from online databases to address this gap. Subsequently, we identified disulfidptosis-related genes from published literature and verified the associated lncRNAs.ResultsThrough univariate, multivariate, and least absolute shrinkage and selection operator (LASSO) regression algorithms analyses, we identified 10 lncRNAs. These were then utilized to construct prognostic prediction models, culminating in a risk-scoring signature. Reliability and validity tests demonstrated that the model effectively discerns glioma patients’ prognosis outcomes. We also analyzed the relationship between the risk score and immune characteristics, and identified several drugs that may be effective for high-risk patients. In vitro experiments revealed that LINC02525 could enhances glioma cells’ migration and invasion capacities. Additionally, knocking down LINC02525 was observed to promote glioma cell disulfidptosis.ConclusionThis study delves into disulfidptosis-related lncRNAs in glioma, offering novel insights into glioma therapeutic strategies

Применение тестовой технологии для диагностики знаний по химии у иностранных слушателей подготовительного отделения

ВЫСШЕЕ МЕДИЦИНСКОЕ ОБРАЗОВАНИЕОБРАЗОВАНИЕ МЕДИЦИНСКОЕИНОСТРАННЫЕ СЛУШАТЕЛИПОДГОТОВИТЕЛЬНОЕ ОТДЕЛЕНИЕХИМИЯ /ОБУЧХИМИЯ (ДИСЦИПЛИНА)ТЕСТЫТЕСТОВЫЕ МЕТОДЫТЕСТОВЫЕ ФОРМЫ КОНТРОЛЯТЕСТОВЫЙ КОНТРОЛЬ ЗНАНИ

Elastic loading enhanced NH3 sensing for surface acoustic wave sensor with highly porous nitrogen doped diamond like carbon film

We proposed a surface acoustic wave (SAW) NH3 gas sensor based on nitrogen doped diamond like carbon (N-DLC) film. The N-DLC film, prepared using a microwave electron cyclotron resonance plasma chemical vapor deposition (ECR-PECVD) method, is highly porous and physically and chemically stable, and have active polar groups on its surface, which can selectively absorb polar NH3 gas molecules. These features of the film lead to the high sensitivity, low noise and excellent stability of the sensor. The sensor can achieve capabilities of in-situ monitoring NH3 in a concentration range from 100 ppb to 100 ppm with fast response (∼5 s) and recovery (∼29 s) at room temperature. The NH3 sensing mechanism is attributed to the decreased porosity of the N-DLC film caused by adsorbed NH3 molecules on its polar groups, which leads an increase of the elastic modulus of the film