Due to their high-entropy effects,the high-entropy(HE)MAX-phase materials improve the comprehen-sive performance of MAX phases,opening up more possibilities for practical engineering applications.However,it is still c...Due to their high-entropy effects,the high-entropy(HE)MAX-phase materials improve the comprehen-sive performance of MAX phases,opening up more possibilities for practical engineering applications.However,it is still challenging to obtain S-containing high-entropy MAX phases because of the high volatilization behavior of sulfur,suffering from issues such as high reaction temperature and long re-action time of traditional synthesis methods.This paper proposes a novel process named as liquid metal assistant self-propagating high-temperature synthesis(LMA-SHS)for efficient synthesis of high-purity S-containing high-entropy MAX-phase materials.Low-melting-point metal(Sn or In)has been introduced into the raw mixture and melted into a liquid phase during the early stage of the SHS reaction.By serv-ing as a“binder”between transition metal atoms of the M-site due to the negative mixing enthalpy,this liquid phase can accelerate mass and heat transfer during the SHS process,ensuring a uniform solid solution of each element and realizing the synthesis of high-purity(TiNbVZr)_(2)SC in an extremely short time.The synthesis method for high-entropy MAX-phase materials developed in this study,i.e.,LMA-SHS,showing very short reaction time,low energy consumption,high yield,and low cost,has the promise to be a general energy-and resource-efficient route towards high-purity HE materials.展开更多
Cytochrome P450 enzymes(P450s or CYPs)are the primary metabolic contributors to the absorption,distribution,metabolism,and excretion(ADME)properties of small-molecule drugs.These enzymes can catalyze various types of ...Cytochrome P450 enzymes(P450s or CYPs)are the primary metabolic contributors to the absorption,distribution,metabolism,and excretion(ADME)properties of small-molecule drugs.These enzymes can catalyze various types of reactions,including metabolic reactions that occur at nitrogen(N)and sulfur(S)sites of small molecules.In this review,we conducted a comprehensive statistical analysis of 294 P450s-mediated small-molecule substrates,among which more than 47%substrates contained N and S.The purpose of the analysis is to elucidate the broad-spectrum cross-reactivity and specificity between these substrates and various CYP isoforms across five reaction types.Our findings reveal that substrates with molecular weights greater than 500 Da or less than 200 Da are predominantly governed by the dominant effect of the CYP isoform’s active sites.In contrast,small-to medium-sized molecules with molecular weights ranging from 200 to 400 Da exhibit a stronger dependence on the types of heteroatoms they contain,with the size of the enzyme’s catalytic site(cavity)playing a negligible role in determining substrate specificity.This review starts from the metabolic mechanisms of P450s-mediated N-and S-containing compounds,and systematically analyzes the structural characteristics of substrates involved in N-dealkylation,N-oxidation,and S-oxidation,as well as their metabolic interactions with P450s.These analyses provide a new perspective for improving the existing understanding of the relationship between the P450s substrate specificity and substrate structural characteristics,and offer a valuable perspective for enhancing drug design and predicting metabolic stability based on the P450s-catalyzed reaction framework.展开更多
基金supported by the Shanghai Local Capacity Building Program(No.23010500700)the Project of Shanghai Municipal Science and Technology Commission(No.22DZ2291100)the Qinglan Project of Jiangsu Province,and the Open Project of Jiangsu Provincial Key Laboratory of Eco-Environmental Materials.
文摘Due to their high-entropy effects,the high-entropy(HE)MAX-phase materials improve the comprehen-sive performance of MAX phases,opening up more possibilities for practical engineering applications.However,it is still challenging to obtain S-containing high-entropy MAX phases because of the high volatilization behavior of sulfur,suffering from issues such as high reaction temperature and long re-action time of traditional synthesis methods.This paper proposes a novel process named as liquid metal assistant self-propagating high-temperature synthesis(LMA-SHS)for efficient synthesis of high-purity S-containing high-entropy MAX-phase materials.Low-melting-point metal(Sn or In)has been introduced into the raw mixture and melted into a liquid phase during the early stage of the SHS reaction.By serv-ing as a“binder”between transition metal atoms of the M-site due to the negative mixing enthalpy,this liquid phase can accelerate mass and heat transfer during the SHS process,ensuring a uniform solid solution of each element and realizing the synthesis of high-purity(TiNbVZr)_(2)SC in an extremely short time.The synthesis method for high-entropy MAX-phase materials developed in this study,i.e.,LMA-SHS,showing very short reaction time,low energy consumption,high yield,and low cost,has the promise to be a general energy-and resource-efficient route towards high-purity HE materials.
基金support from the National Natural Science Foundation of China(8227131503).
文摘Cytochrome P450 enzymes(P450s or CYPs)are the primary metabolic contributors to the absorption,distribution,metabolism,and excretion(ADME)properties of small-molecule drugs.These enzymes can catalyze various types of reactions,including metabolic reactions that occur at nitrogen(N)and sulfur(S)sites of small molecules.In this review,we conducted a comprehensive statistical analysis of 294 P450s-mediated small-molecule substrates,among which more than 47%substrates contained N and S.The purpose of the analysis is to elucidate the broad-spectrum cross-reactivity and specificity between these substrates and various CYP isoforms across five reaction types.Our findings reveal that substrates with molecular weights greater than 500 Da or less than 200 Da are predominantly governed by the dominant effect of the CYP isoform’s active sites.In contrast,small-to medium-sized molecules with molecular weights ranging from 200 to 400 Da exhibit a stronger dependence on the types of heteroatoms they contain,with the size of the enzyme’s catalytic site(cavity)playing a negligible role in determining substrate specificity.This review starts from the metabolic mechanisms of P450s-mediated N-and S-containing compounds,and systematically analyzes the structural characteristics of substrates involved in N-dealkylation,N-oxidation,and S-oxidation,as well as their metabolic interactions with P450s.These analyses provide a new perspective for improving the existing understanding of the relationship between the P450s substrate specificity and substrate structural characteristics,and offer a valuable perspective for enhancing drug design and predicting metabolic stability based on the P450s-catalyzed reaction framework.
