Molecular design, synthesis strategies and recent advances of hydrogels for wound dressing applications

With the changes in the modern disease spectrum,pressure ulcers,diabetic feet,and vascular-derived diseases caused refractory wounds is increasing rapidly.The development of wound dressings has partly improved the effect of wound management.However,traditional wound dressings can only cover the wound and block bacteria,but are generally powerless to recurrent wound infection and tissue healing.There is an urgent need to develop a new type of wound dressing with comprehensive performance to achieve multiple effects such as protecting the wound site from the external environment,absorbing wound exudate,anti-inflammatory,antibacterial,and accelerating wound healing process.Hydrogel wound dressings have the aforementioned characteristics,and can keep the wound in a moist environment because of the high water content,which is an ideal choice for wound treatment.This review introduces the wound healing process and the development and performance advantages of hydrogel wound dressings.The choice of different preparation materials gives the particularities of different hydrogel wound dressings.It also systematically explains the main physical and chemical crosslinking methods for hydrogel synthesis.Besides,in-depth discussion of four typical hydrogel wound dressings including double network hydrogels,nanocomposite hydrogels,drug-loaded hydrogels and smart hydrogels fully demonstrates the feasibility of developing hydrogels as wound dressing products and their future development trends.

Molecular design,synthesis and biological activities of amidines as new ketol-acid reductoisomerase inhibitors

Diamidine （A） was identified in our in vitro bio-assay as a possible inhibitor of ketol-acid reductoisomerase （KARI） from the ACD database search based on the known three-dimensional crystal structure of KARI. An investigation on interaction of A on KARI active sites, led to the design and synthesis of 15 novel monoamidines. Some of those showed better biological activity than A on rice KARI （in vitro） and in greenhouse herbicidal tests （in vivo）. The structure-biological activity relationship was investigated, which provides valuable information to further study of potential KARI inhibitors.

INTERFACIAL MOLECULAR DESIGN OF A RIGID- PARTICLE TOUGHENED POLYAMIDE 6 COMPOSITE

The effects of interfacial modifier on the mechanical properties of kaolin-filled polyamide 6 (PA6) have been studied. The interracial interaction between polyamide 6 and kaolin has been character ized by means of infrared spectroscopy (IR) and scanning electron microscopy (SEM). The results show that the role of the interracial modifier lies in forming an elastic interlayer with good adhesion between kaolin and PA 6. A composite with high impact strength, high tensile strength and high elastic modulus can be obtained by inserting the elastic interfacial modifier into the rigid-particle-filled polymer system.

Molecular design towards two-dimensional electron acceptors for efficient non-fullerene solar cells

Non-fullerene polymer solar cells(NF-PSCs) have gained wide attention recently. Molecular design of non-fullerene electron acceptors effectively promotes the photovoltaic performance of NF-PSCs. However,molecular electron acceptors with 2-dimensional(2 D) configuration and conjugation are seldom reported.Herein, we designed and synthesized a series of novel 2 D electron acceptors for efficient NF-PSCs. With rational optimization on the conjugated moieties in both vertical and horizontal direction, these 2 D electron acceptors showed appealing properties, such as good planarity, full-spectrum absorption, high absorption extinction coefficient, and proper blend morphology with donor polymer. A high PCE of 9.76%was achieved for photovoltaic devices with PBDB-T as the donor and these 2 D electron acceptors. It was also found the charge transfer between the conjugated moieties in two directions of these 2 D molecules contributes to the utilization of absorbed photos, resulting in an exceptional EQE of 87% at 730 nm. This work presents rational design guidelines of 2 D electron acceptors, which showed great promise to achieve high-performance non-fullerene polymer solar cells.

Molecular Design of Conjugated Small Molecule Nanoparticles for Synergistically Enhanced PTT/PDT

Simultaneous photothermal therapy(PTT)and photodynamic therapy(PDT)is beneficial for enhanced cancer therapy due to the synergistic effect.Conventional materials developed for synergistic PTT/PDT are generally multicomponent agents that need complicated preparation procedures and be activated by multiple laser sources.The emerging monocomponent diketopyrrolopyrrole(DPP)-based conjugated small molecular agents enable dual PTT/PDT under a single laser irradiation,but suffer from low singlet oxygen quantum yield,which severely restricts the therapeutic efficacy.Herein,we report acceptor-oriented molecular design of a donor-acceptor-donor(D-A-D)conjugated small molecule(IID-ThTPA)-based phototheranostic agent,with isoindigo(IID)as selective acceptor and triphenylamine(TPA)as donor.The strong D-A strength and narrow singlet-triplet energy gap endow IID-ThTPA nanoparticles(IID-ThTPA NPs)high mass extinction coefficient(18.2 L g^-1 cm^-1),competitive photothermal conversion efficiency(35.4%),and a dramatically enhanced singlet oxygen quantum yield(84.0%)comparing with previously reported monocomponent PTT/PDT agents.Such a high PTT/PDT performance of IID-ThTPA NPs achieved superior tumor cooperative eradicating capability in vitro and in vivo.

Molecular Design and Electronic Structure of Polynuclear Rare Earth Complexes and Clusters

Studies on the electronic structure,molecular design,syntheses of some novel series of tetranuclear rare earth complexes in our laboratory have been reviewed.Spin-unrestricted localized INDO method was used to calculate the electronic structure and the chemical bonding in the typical rare earth cluster Sc[Sc_6Cl_(12)Co]was discussed.

Receptor-based Molecular Designs of DABO Derivatives as HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors

A series of 46 dihydro-alkoxy-benzyl-oxopyrimidines （DABOs）, a class of highly potent non-nucleoside reverse transcriptase inhibitors （NNRTIs）, was studied by molecular docking followed by comparative molecular field analysis （CoMFA） and comparative molecular similarity index analysis （CoMSIA）. The results showed that the H-bonding interactions between the C=O and NH of the pyrimidine ring and Lys101, hydrophobic interactions between R, R1, X sites of ligands and neighboring amino acid residuals, and the electrostatic interactions between ligands and His235 and Lys101 residues were the dominant factors affecting the binding affinities. Based on an optimal docking conformation, 3D-QSAR models of 46 DABO derivatives were developed. The r^2 and cross-validated r^2 （q^2） of an optimal CoMSIA model were 0.862 and 0.532, respectively. Based on the QSAR studies, 9 new compounds were designed by the method of LeapFrog. The binding energies and docking scores （GScore） of 9 new compounds were better than that of a template molecule with the highest observed activity. The results showed that the molecular designs of DABOs should be focused on the hydrophobic interactions with the bottom of the binding pocket as well as van der Waals interactions with the entrance of binding pocket.

A Property Based Approach for Simultaneous Process and Molecular Design

在这个工作，性质聚类技术和组贡献方法被联合启用过程表演要求和分子性质限制的同时的考虑。用这方法论，过程设计问题被解决识别相应于发达方法论的重要优点是为问题，那能被仅仅三个性质令人满意地描述的需要的过程 performance.A 的性质目标，进程和分子设计问题能同时在一个三元图解，不管多少，分子的碎片在搜索空间被包括上视觉上被解决。在第三的簇图上，如果作为分离的值或作为一个区域给，如果作为间隔给，目标性质作为单个点被代表。候选人部件的结构和身份然后被联合或“混合”分子的碎片直到产生性质匹配目标识别。

Quantum chemical aided molecular design of ionic liquids as green electrolytes for electrodeposition of active metals

Quantum chemical calculation was used to estimate the reduction potentials of 25 organic cations and the oxidation potentials of 11 anions.This information was used to select promising cations and anions for the preparation of ionic liquids as green electrolytes for electrodeposition of active metals.The reasonable linear correlations between the lowest unoccupied molecular orbital(LUMO)energies and the reduction potentials of cations,and the linear relationships between the oxidation potentials and the highest occupied molecular orbital(HOMO)energies of anions were obtained.The orders of electrochemical stability for cations and anions being obtained agree well with the experimental measurements.The suitable ionic liquids with sufficiently wide electrochemical windows for electrodeposition of active metals are suggested to be[Emim]NTf2,[Bmim]NTf2,[Bmim]BF4, [Bmim]PF6,[Bmim]CTf3,[Emim]BF4,[Emim]PF6,[Emim]CTf3..

Molecular design for enhanced spin transport in molecular semiconductors

Molecular semiconductors(MSCs),characterized by a longer spin lifetime than most of other materials due to their weak spin relaxation mechanisms,especially at room temperature,together with their abundant chemical tailorability and flexibility,are regarded as promising candidates for spintronic applications.Molecular spintronics,as an emerging subject that utilizes the unique properties of MSCs to study spin-dependent phenomena and properties,has attracted wide attention.In molecular spintronic devices,MSCs play the role as medium for information transport,process,and storage,in which the efficient spin inject–transport process is the prerequisite.Herein,we focus mainly on summarizing and discussing the recent advances in theoretical principles towards spin transport of MSCs in terms of the injection of spin-polarized carriers through the ferromagnetic metal/MSC interface and the subsequent transport within the MSC layer.Based on the theoretical progress,we cautiously present targeted design strategies of MSCs that contribute to the optimization of spin-transport efficiency and give favorable approaches to exploring accessional possibilities of spintronic materials.Finally,challenges and prospects regarding current spin transport are also presented,aiming to promote the development and application of the rosy and energetic field of molecular spintronics.

Molecular engineering binuclear copper catalysts for selective CO_(2) reduction to C_(2) products

Molecular copper catalysts serve as exemplary models for correlating the structure-reaction-mechanism relationship in the electrochemical CO_(2) reduction(eCO_(2)R),owing to their adaptable environments surrounding the copper metal centres.This investigation,employing density functional theory calculations,focuses on a novel family of binuclear Cu molecular catalysts.The modulation of their coordination configuration through the introduction of organic groups aims to assess their efficacy in converting CO_(2) to C_(2)products.Our findings highlight the crucial role of chemical valence state in shaping the characteristics of binuclear Cu catalysts,consequently influencing the eCO_(2)R behaviour,Notably,the Cu(Ⅱ)Cu(Ⅱ)macrocycle catalyst exhibits enhanced suppression of the hydrogen evolution reaction(HER),facilitating proton trans fer and the eCO_(2)R process.Fu rthermore,we explo re the impact of diverse electro n-withdrawing and electron-donating groups coordinated to the macrocycle(R=-F,-H,and-OCH_3)on the electron distribution in the molecular catalysts.Strategic placement of-OCH_3 groups in the macrocycles leads to a favourable oxidation state of the Cu centres and subsequent C-C coupling to form C_(2) products.This research provides fundamental insights into the design and optimization of binuclear Cu molecular catalysts for the electrochemical conversion of CO_(2) to value-added C_(2) products.

CoMFA Model of Anti-tumor Activity for Fluoroquinolon-3-yl s-Triazole Sulfide-ketone Derivatives and Implications for Molecular Design

Comparative molecular field analysis(CoMFA)techniques were used to perform three-dimensional quantitative structure-activity relationship(3D-QSAR)studies on the anti-tumor activity(pIH and pIC)of 28 fluoroquinolon-3-yl s-triazole sulfide-ketone derivatives(FQTSDs)against two cancer cell lines,including human hepatoma Hep-3B cells and human pancreatic cancer Capan-1 cells.23 compounds were randomly selected as the training set to establish the prediction models,which were verified by the test set of 6 compounds containing template molecule.The obtained cross-validation(Rcv2)and non-cross-validation correlation coefficients(R2)of the CoMFA models were 0.477 and 0.850 for pIH,and 0.421 and 0.836 for pIC,respectively.The contributions of steric and electrostatic fields to pIH were determined to be 48.1%and 51.9%,and those to pIC were 49.4%and 50.6%,respectively.The CoMFA models were then used to predict the activities of the compounds in the training and testing sets,and the models had a strong stability and good predictability.Based on the 3D contour maps,four novel FQTSDs with a higher anti-tumor activity were designed.However,the effectiveness of these novel FQTSDs is still needed to be verified by experimental results.

Toward Rational and Modular Molecular Design in Soft Matter Engineering

This essay discusses some preliminary thoughts on the development of a rational and modular approach for molecular design in soft matter engineering and proposes ideas of structural and functional synthons for advanced functional materials. It echoes the Materials Genome Initiative by practicing a tentative retro-functional analysis （RFA） scheme. The importance of hierarchical structures in transferring and amplifying molecular functions into macroscopic properties is recognized and emphasized. According to the role of molecular segments in final materials, there are two types of building blocks： structural synthon and functional synthon. Guided by a specific structure for a desired function, these synthons can be modularly combined in various ways to construct molecular scaffolds. Detailed molecular structures are then deduced, designed and synthesized precisely and modularly. While the assembled structure and property may deviate from the original design, the study may allow further refinement of the molecular design toward the target function, The strategy has been used in the development of soft fullerene materials and other giant molecules. There are a few aspects that are not yet well addressed： （1） function and structure are not fully decoupled and （2） the assembled hierarchical structures are sensitive to secondary interactions and molecular geometries across different length scales. Nevertheless, the RFA approach provides a starting point and an alternative thinking pathway by provoking creativity with considerations from both chemistry and physics. This is particularly useful for engineering soft matters with supramolecular lattice formation, as in giant molecules, where the synthons are relatively independent of each other.

QSAR Study and Molecular Design of Isoquinolone Derivative JNK1 Inhibitors

JNK1 is a drug target for the treatment of type 2 diabetes,and it plays a key mediator role in metabolic disorders.In this paper,holographic quantitative structure-activity relationship(HQSAR)technology and Topomer comparative molecular field analysis(Topomer CoMFA)technology are used to analyze the quantitative structure-activity relationship(QSAR)of 39 isoquinolone derivatives.The cross validation correlation coefficient(q^(2))is 0.696(Topomer CoMFA)and 0.826(HQSAR),and the non-cross validation correlation coefficient(r^(2))is 0.935(Topomer CoMFA)and 0.987(HQSAR).The results showed that the models have good stability and predictive ability.The Topomer search module was applied to define high contribution fragments in the ZINC database,designing 20 new isoquinolone compounds with theoretically high inhibitory activity.The molecular docking was carried out to explore the interaction between the ligand and target JNK1 protein.This study can provide a theoretical basis for the design of new JNK1 inhibitors.

Design of bio-oil additives via molecular signature descriptors using a multi-stage computer-aided molecular design framework

Direct application of bio-oil from fast pyrolysis as a fuel has remained a challenge due to its undesirable attributes such as low heating value,high viscosity,high corrosiveness and storage instability.Solvent addition is a simple method for circumventing these disadvantages to allow further processing and storage.In this work,computer-aided molecular design tools were developed to design optimal solvents to upgrade bio-oil whilst having low environmental impact.Firstly,target solvent requirements were translated into measurable physical properties.As different property prediction models consist different levels of structural information,molecular signature descriptor was used as a common platform to formulate the design problem.Because of the differences in the required structural information of different property prediction models,signatures of different heights were needed in formulating the design problem.Due to the combinatorial nature of higher-order signatures,the complexity of a computer-aided molecular design problem increases with the height of signatures.Thus,a multi-stage framework was developed by developing consistency rules that restrict the number of higher-order signatures.Finally,phase stability analysis was conducted to evaluate the stability of the solvent-oil blend.As a result,optimal solvents that improve the solvent-oil blend properties while displaying low environmental impact were identified.

Molecular Design and Performance Studies of 4-(1,2,4-Triazole-5-yl)Furazan Derivatives as Promising Energetic Materials

In this paper,eight 4-(1,2,4-triazole-5-yl)furazan(TZFZ)derivatives were designed,and the molecular configurations of TZFZ compounds were optimized by using the B3LYP/6-311+G*level.Meanwhile,the detonation performance,density,impact sensitivity,heat of formation and oxygen balance have been investigated.The results clearly and intuitively illustrate that the introduction of-NO2 and coordination oxygen plays a pivotal role in increasing the density and heat of formation.In summary,the properties of these compounds are better than the traditional explosives RDX and TNT,especially the density and detonation pressure.Energetic evaluations showed that compounds B1(P=36.73 GPa;D=8.98 km·s^(-1),ρ=1.88 g·cm^(-3))and B7(P=38.51 GPa;D=9.17 km·s-1,ρ=1.90 g·cm^(-3))could be seen as promising candidates of energetic insensitive compounds with remarkable performance.

Deep-red and near-infrared organic lasers based on centrosymmetric molecules with excited-state intramolecular double proton transfer activity

Organic lasers that emit light in the deep-red and near-infrared(NIR)region are of essential importance in laser communication,night vision,bioimaging,and information-secured displays but are still challenging because of the lack of proper gain materials.Herein,a new molecular design strategy that operates by merging two excited-state intramolecular proton transfer-active molecules into one excited-state double proton transfer(ESDPT)-active molecule was demonstrated.Based on this new strategy,three new materials were designed and synthesized with two groups of intramolecular resonance-assisted hydrogen bonds,in which the ESDPT process was proven to proceed smoothly based on theoretical calculations and experimental results of steady-state and transient spectra.Benefiting from the effective six-level system constructed by the ESDPT process,all newly designed materials showed low threshold laser emissions at approximately 720 nm when doped in PS microspheres,which in turn proved the existence of the second proton transfer process.More importantly,our well-developed NIR organic lasers showed high laser stability,which can maintain high laser intensity after 12000 pulse lasing,which is essential in practical applications.This work provides a simple and effective method for the development of NIR organic gain materials and demonstrates the ESDPT mechanism for NIR lasing.

Emergent strategies for inverse molecular design

Molecular design is essential and ubiquitous in chemistry,physics,biology,and material science.The immense space of available candidate molecules requires novel optimization strategies and algorithms for exploring the space and achieving efficient and effective molecular design.This paper summarizes the current progress toward developing practical theoretical optimization schemes for molecular design.In particular,we emphasize emergent strategies for inverse molecular design.Several representative design examples,based on recently developed strategies,are described to demonstrate the principles of inverse molecular design.

Prediction of mutant activity and its application in molecular design of tumor necrosis factor-a

Two models for prediction of the activity and stability of site-directed mutagenesis on tumor necrosis factor-α are established. The models are based on straightforward structural considerations, which do not require the elaboration of site-directed mutagenesis on the protein core and the hydrophobic surface area by analyzing the properties of the mutated amino acid residues. The reliabilities of the models have been tested by analyzing the mutants of tumor necrosis factor-α (TNF-α) whose two leucine residues (L29, L157) were mutated. Based on these models, a TNF-α mutant with high activity was created by molecular design.

Bio-rational design of photosystem Ⅱ inhibitors (Ⅷ)——Molecular design, synthesis and inhibitory activity of acrylates (acrylamides)

Molecular modeling of acrylates (acrylamides) with D1 protein of Pisum sativum is presented. Studies show that the binding force mainly includes H-bond interaction, Van der Waals and π-ring stacking interaction. It was found that SER 268 in D1 protein might be an important binding site. It is important for high inhibitory activity of compounds whether an electronegative atom in alkyl of ester linkage could make H-bond interaction with SER 268 in D1 protein. Thus some new acrylates (acrylamides) were designed and synthesized, Bioassay indicated that these new compounds showed expected Hill reaction inhibitory activity.