The roles of computer-aided drug synthesis in drug development

With the improvements in computer computing ability,data accumulation and rapid algorithm development,the integration of artificial intelligence(AI)and drug synthesis has been accelerated,significantly improving the design and synthesis of drug molecules.Recently,data-driven computer-aided synthesis tools have been quickly and widely applied in retrosynthetic analysis,reaction prediction and automated synthesis,which can effectively accelerate the process of drug discovery and development and improve the quality of designed and synthesized drug molecules.Here,we review the development and applications of computer-aided synthesis technology and introduce recent advances in computer-aided drug development from three aspects:computer-aided drug design,computer-aided drug synthesis route design and computer-aided intelligent drug synthesis machines.Furthermore,the challenges and opportunities of computer-aided drug synthesis technology are discussed.

Nanozyme-activating prodrug therapies:A review

Enzyme prodrug therapies(EPTs)have been intensively explored as attractive approaches to selective activation of systemically administered benign prodrugs by the exogenous enzymes or enzymes expressed at the desired target site,thus achieving localized,site-specific therapeutic effect.Many effective strategies(e.g.,antibody-,viral-,gene-,as well as polymer-directed EPT)have been developed for enzyme localization to locally activate systemically administered benign prodrugs.Nevertheless,intrinsic limitations(e.g.,complex intracellular environment and catalyst instability)make the practical application of EPT strategies a task that presents itself as highly challenging.As a promising alternative to natural enzyme,nanozyme has attracted substantial attention since its discovery in 2007,mainly due to the advantages of robust catalytic activity,high stability,low cost,and facile synthesis.Recently,nanozyme-activated prodrug strategies bring a new opportunity for targeted therapy,referred to as nanozyme-activating prodrug therapies.This review focuses on recently reported nanozyme-activated prodrug strategies,aiming to provide some new insights into the potential applications in site-specific drug synthesis.

Applications of covalent organic frameworks(COFs)：From gas storage and separation to drug delivery

Covalent organic frameworks（COFs） are an emerging class of porous covalent organic structures whose backbones were composed of light elements（B,C,N,O,Si） and linked by robust covalent bonds to endow such material with desirable properties,i.e.,inherent porosity,well-defined pore aperture,ordered channel structure,large surface area,high stability,and multi-dimension.As expected,the abovementioned properties of COFs broaden the applications of this class of materials in various fields such as gas storage and separation,catalysis,optoelectronics,sensing,small molecules adsorption,and drug delivery.In this review,we outlined the synthesis of COFs and highlighted their applications ranging from the initial gas storage and separation to drug delivery.

Nanostructured hollow spheres of hydroxyapatite： preparation and potential application in drug delivery

A solvothermal method has been successfully used to prepare nanostructured hydroxyapatite （HA） hollow spheres with average diameters of about 500 nm and shell thicknesses of about 100 nm in a glycerin/water mixed solvent. Transmission electron microscopy （TEM） and field-emission scanning electron microscopy （FESEM） images show that the shells of the HA hollow spheres are actually composed of nanosheets with thicknesses of about 10 nm. By tuning the glycerin/water volume ratio, two other kinds of HA solid spheres with average diameters of about 6 or 20 pm were assembled from nanoflakes. The properties of the different kinds of spheres as drug delivery carriers were evaluated. Ibuprofen （IBU） was chosen as the model drug to load into the HA samples. The nanostructured HA samples showed a slow and sustained release of IBU. The HA hollow spheres exhibited a higher drug loading capacity and more favorable release properties than the HA solid spheres and thus are very promising for controlled drug release applications.

Single-atomic-site iron on N-doped carbon for chemoselective reduction of nitroarenes

A facile,gram-scale and sustainable approach has been established for the synthesis of single-atomic-site iron on N-doped carbon(Fe_(SA)@NC-20A)via the pyrolysis of aniline modified FeZn-ZIFs,in which the synthesis of zeolitic imidazolate frameworks(ZIFs)can be accomplished in water at room temperature,and no acid etching is required.The as-synthesized catalyst exhibits better performance on the chemoselective hydrogenation of nitroarenes with a broad substrate scope(turnover frequency(TOF)up to 1,727 h^(-1),23 examples)than most of previously reported works.Based on high-angle annular dark field scanning transmission microscopy(HAADF-STEM)images in combination with X-ray photoelectron spectroscopy(XPS),X-ray absorption spectroscopy(XAS),electron spin resonance(ESR),and Mossbauer spectroscopy,Fe is dispersed as single atoms via forming FeNx(x=4-6).This work not only determines the active sites of FesA@NC-20A for hydrogenation(FeN4),but also proposes tentative pathways for both N-H activation of hydrazine and the reduction of nitroarene on FeN4 site,both of which are the key steps for the hydrogenation of nitroarenes.In addition,this catalyst shows excellent stability,and no significant activity degradation is observed when recycling for 10 times or restoring in air for 2 months.