Complex diseases do not always follow gradual progressions.Instead,they may experience sudden shifts known as critical states or tipping points,where a marked qualitative change occurs.Detecting such a pivotal transit...Complex diseases do not always follow gradual progressions.Instead,they may experience sudden shifts known as critical states or tipping points,where a marked qualitative change occurs.Detecting such a pivotal transition or pre-deterioration state holds paramount importance due to its association with severe disease deterioration.Nevertheless,the task of pinpointing the pre-deterioration state for complex diseases remains an obstacle,especially in scenarios involving high-dimensional data with limited samples,where conventional statistical methods frequently prove inadequate.In this study,we introduce an innovative quantitative approach termed sample-specific causality network entropy(SCNE),which infers a sample-specific causality network for each individual and effectively quantifies the dynamic alterations in causal relations among molecules,thereby capturing critical points or pre-deterioration states of complex diseases.We substantiated the accuracy and efficacy of our approach via numerical simulations and by examining various real-world datasets,including single-cell data of epithelial cell deterioration(EPCD)in colorectal cancer,influenza infection data,and three different tumor cases from The Cancer Genome Atlas(TCGA)repositories.Compared to other existing six single-sample methods,our proposed approach exhibits superior performance in identifying critical signals or pre-deterioration states.Additionally,the efficacy of computational findings is underscored by analyzing the functionality of signaling biomarkers.展开更多
Herein, we reported an efficient and straightforward method to realize desaturated β-C(sp^(3))-H sulfonylation andphosphonylation of cyclic amines driven by electrochemistry using catalytic amounts of CP_(2)Fe as the...Herein, we reported an efficient and straightforward method to realize desaturated β-C(sp^(3))-H sulfonylation andphosphonylation of cyclic amines driven by electrochemistry using catalytic amounts of CP_(2)Fe as the redoxmediator. This protocol which had good functional group compatibility, provided the desired enaminyl sulfoneand enaminyl phosphine oxide products with high chemo- and regio-selectivity under mild conditions. Severalmechanistic studies have suggested that cyclic amines underwent multiple single-electron oxidation and deprotonation processes, followed by a capture step involving either a sulfonyl radical or a phosphonyl radical, ultimately leading to the desired products.展开更多
The study of a Mitsunobu reaction is an important topic.Denton and co-workers first reported a novel(2-hydroxybenzyl)diphenylphosphine oxide for realizing the catalytic Mitsunobu reaction via a five-membered phosphoni...The study of a Mitsunobu reaction is an important topic.Denton and co-workers first reported a novel(2-hydroxybenzyl)diphenylphosphine oxide for realizing the catalytic Mitsunobu reaction via a five-membered phosphonium species.However,it is still worth investigating how to improve catalysts with higher efficiency.Guided by computational and experimental studies,we designed a new type of biphenyl-based phosphine oxide that would form a six-membered phosphonium species as a key intermediate to trigger the catalytic Mitsunobu reaction with a lower barrier of the rate-determining step(30.3 kcal/mol).DFT calculations revealed that only trans dehydration was participated in our catalytic progress and a strongπ-πinteraction and small spatial constraint of TS-V were crucial for high behavior.This readily accessible,highly stable,easily recyclable and efficient catalyst would boost the catalytic Mitsunobu reaction.展开更多
A ruthenium-catalyzed electrochemical dehydrogenative C(sp^(2))H acyloxylation of aniline derivatives with carboxylic acids has been developed.Electric current is used to recycle the active ruthenium-based catalyst an...A ruthenium-catalyzed electrochemical dehydrogenative C(sp^(2))H acyloxylation of aniline derivatives with carboxylic acids has been developed.Electric current is used to recycle the active ruthenium-based catalyst and promote H_(2) evolution.This method significantly expands the scope and enhances the selectivity of metal-electron catalyzed mono-and di-acyloxylations,which remain challenged.Our findings allowed mono-selectivity in broadly effective late-stage diversification of structurally complex drugs and natural product molecules,tolerating drugs,natural products and amino acids.The method and its underlying strategy are expected to have widespread uses in functional aniline synthesis and drug discovery process.展开更多
基金supported by National Natural Science Foundation of China(nos.T2341022,12322119,62172164,and 12271180)Guangdong Provincial Key Laboratory of Human Digital Twin(2022B1212010004)+2 种基金Educational Commission of Guangdong Province of China(2023KQNCX073)the Natural Science Foundation of Guangdong Province of China(2022A-1515110759,and 2023A1515110558)Fundamental Research Funds for the Central Universities(2023ZYGXZR077).
文摘Complex diseases do not always follow gradual progressions.Instead,they may experience sudden shifts known as critical states or tipping points,where a marked qualitative change occurs.Detecting such a pivotal transition or pre-deterioration state holds paramount importance due to its association with severe disease deterioration.Nevertheless,the task of pinpointing the pre-deterioration state for complex diseases remains an obstacle,especially in scenarios involving high-dimensional data with limited samples,where conventional statistical methods frequently prove inadequate.In this study,we introduce an innovative quantitative approach termed sample-specific causality network entropy(SCNE),which infers a sample-specific causality network for each individual and effectively quantifies the dynamic alterations in causal relations among molecules,thereby capturing critical points or pre-deterioration states of complex diseases.We substantiated the accuracy and efficacy of our approach via numerical simulations and by examining various real-world datasets,including single-cell data of epithelial cell deterioration(EPCD)in colorectal cancer,influenza infection data,and three different tumor cases from The Cancer Genome Atlas(TCGA)repositories.Compared to other existing six single-sample methods,our proposed approach exhibits superior performance in identifying critical signals or pre-deterioration states.Additionally,the efficacy of computational findings is underscored by analyzing the functionality of signaling biomarkers.
基金National Natural Science Foundation of China(Nos.22178315,22378363,22078298 and 21978271)the Natural Science Foundation of Zhejiang Province of China(No.LY21B020007)+1 种基金China Postdoctoral Science Foundation(No.2022M712824)Key Research and Development Program of Zhejiang Province(No.2022C03169)for financial support.
文摘Herein, we reported an efficient and straightforward method to realize desaturated β-C(sp^(3))-H sulfonylation andphosphonylation of cyclic amines driven by electrochemistry using catalytic amounts of CP_(2)Fe as the redoxmediator. This protocol which had good functional group compatibility, provided the desired enaminyl sulfoneand enaminyl phosphine oxide products with high chemo- and regio-selectivity under mild conditions. Severalmechanistic studies have suggested that cyclic amines underwent multiple single-electron oxidation and deprotonation processes, followed by a capture step involving either a sulfonyl radical or a phosphonyl radical, ultimately leading to the desired products.
基金financially supported by the National Natural Science Foundation of China(Nos.22078298,21978271 and 22178315)Natural Science Foundation of Zhejiang Province(No.LY21B020007)+1 种基金China Postdoctoral Science Foundation(No.2022M712824)Key Research and Development Program of Zhejiang Province(No.2023C03117).
文摘The study of a Mitsunobu reaction is an important topic.Denton and co-workers first reported a novel(2-hydroxybenzyl)diphenylphosphine oxide for realizing the catalytic Mitsunobu reaction via a five-membered phosphonium species.However,it is still worth investigating how to improve catalysts with higher efficiency.Guided by computational and experimental studies,we designed a new type of biphenyl-based phosphine oxide that would form a six-membered phosphonium species as a key intermediate to trigger the catalytic Mitsunobu reaction with a lower barrier of the rate-determining step(30.3 kcal/mol).DFT calculations revealed that only trans dehydration was participated in our catalytic progress and a strongπ-πinteraction and small spatial constraint of TS-V were crucial for high behavior.This readily accessible,highly stable,easily recyclable and efficient catalyst would boost the catalytic Mitsunobu reaction.
基金We thank the National Natural Science Foundation of China(Nos.22078298,21978271,21706234 and 21676253)the Natural Science Foundation of Zhejiang Province of China(No.LY19B060011)for financial support.
文摘A ruthenium-catalyzed electrochemical dehydrogenative C(sp^(2))H acyloxylation of aniline derivatives with carboxylic acids has been developed.Electric current is used to recycle the active ruthenium-based catalyst and promote H_(2) evolution.This method significantly expands the scope and enhances the selectivity of metal-electron catalyzed mono-and di-acyloxylations,which remain challenged.Our findings allowed mono-selectivity in broadly effective late-stage diversification of structurally complex drugs and natural product molecules,tolerating drugs,natural products and amino acids.The method and its underlying strategy are expected to have widespread uses in functional aniline synthesis and drug discovery process.
