Crystal Structure Of Complex Research Articles

Thermal transport in metal halide perovskites and other third-generation photovoltaic materials

Third-generation photovoltaic materials, including metal halide perovskites (MHPs), colloidal quantum dots (QDs), copper zinc tin sulfide (CZTS), and organic semiconductors, among others, have become attractive in the past two decades. Unlike their first- and second-generation counterparts, these advanced materials boast properties beyond mere photovoltaic performance, such as mechanical flexibility, light weight, and cost-effectiveness. Meanwhile, these materials possess more intricate crystalline structures that aid in understanding and predicting their transport properties. In particular, the distinctive phonon dispersions in MHPs, the layered architecture in quasi-two-dimensional (2D) perovskites, the strong quantum confinement in QDs, and the complex crystal structures interspersed with abundant disorders in quaternary CZTS result in unique and sometimes anomalous thermal transport behaviors. Concurrently, the criticality of thermal management in applications such as photovoltaics, thermoelectrics, light emitting diodes, and photodetection devices has received increased recognition, considering that many of these third-generation photovoltaic materials are not good thermal conductors. Effective thermal management necessitates precise measurement, advanced modeling, and a profound understanding and interpretation of thermal transport properties in these novel materials. In this review, we provide a comprehensive summary of various techniques for measuring thermal transport properties of these materials and discuss the ultralow thermal conductivities of three-dimensional (3D) MHPs, superlattice-like thermal transport in 2D perovskites, and novel thermal transport characteristics inherent in QDs and CZTS. By collecting and comparing the literature-reported results, we offer a thorough discussion on the thermal transport phenomenon in these materials. The collective understanding from the literature in this area, as reviewed in this article, can provide guidance for improving thermal management across a wide spectrum of applications extending beyond photovoltaics.

Structures of a DNA Polymerase Caught while Incorporating Responsive Dual-Functional Nucleotide Probes.

Functionalizing nucleic acids using DNA polymerases is essential in biophysical and biotechnology applications. This study focuses on understanding how DNA polymerases recognize and incorporate nucleotides with diverse chemical modifications, aiming to develop advanced nucleotide probes. We present the crystal structures of ternary complexes of Thermus aquaticus DNA polymerase (KlenTaq) with C5-heterocycle-modified environment-sensitive 2'-deoxyuridine-5'-triphosphate (dUTP) probes. These nucleotides include SedUTP, BFdUTP and FBFdUTP, which bear selenophene, benzofuran and fluorobenzofuran, respectively, at the C5 position of uracil, and exhibit high conformational sensitivity. SedUTP and FBFdUTP serve as dual-app probes, combining a fluorophore with X-ray anomalous scattering Se or 19F NMR labels. Our study reveals that the size of the heterocycle influences how DNA polymerase families A and B incorporate these modified nucleotides during single nucleotide incorporation and primer extension reactions. Remarkably, FBFdUTP's responsiveness enabled real-time monitoring of the binary complex formation and polymerase activity through fluorescence and 19F NMR. Comparative analysis of incorporation profiles, fluorescence, 19F NMR data, and crystal structures of ternary complexes highlights the enzyme's plasticity. Key insights are provided into the role of gatekeeper amino acids (Arg660 and Arg587) in accommodating and processing these modified substrates, offering a structural basis for next-generation nucleotide probe development.

Structures of a DNA Polymerase Caught while Incorporating Responsive Dual‐Functional Nucleotide Probes

Functionalizing nucleic acids using DNA polymerases is essential in biophysical and biotechnology applications. This study focuses on understanding how DNA polymerases recognize and incorporate nucleotides with diverse chemical modifications, aiming to develop advanced nucleotide probes. We present the crystal structures of ternary complexes of Thermus aquaticus DNA polymerase (KlenTaq) with C5‐heterocycle‐modified environment‐sensitive 2′‐deoxyuridine‐5′‐triphosphate (dUTP) probes. These nucleotides include SedUTP, BFdUTP and FBFdUTP, which bear selenophene, benzofuran and fluorobenzofuran, respectively, at the C5 position of uracil, and exhibit high conformational sensitivity. SedUTP and FBFdUTP serve as dual‐app probes, combining a fluorophore with X‐ray anomalous scattering Se or 19F NMR labels. Our study reveals that the size of the heterocycle influences how DNA polymerase families A and B incorporate these modified nucleotides during single nucleotide incorporation and primer extension reactions. Remarkably, FBFdUTP's responsiveness enabled real‐time monitoring of the binary complex formation and polymerase activity through fluorescence and 19F NMR. Comparative analysis of incorporation profiles, fluorescence, 19F NMR data, and crystal structures of ternary complexes highlights the enzyme's plasticity. Key insights are provided into the role of gatekeeper amino acids (Arg660 and Arg587) in accommodating and processing these modified substrates, offering a structural basis for next‐generation nucleotide probe development.

Application of enaminone ruthenium(II) complexes as catalysts in the transfer hydrogenation of ketones

This study reported the synthesis of two new ligands (1,2) and their Ru(II)-enaminone complexes (3,4). The Ru(II) complexes were obtained from the reaction of the [RuCl2(p-cymene)]2 dimers with the new enaminone derivative ligands (1,2). The use of standard spectroscopy techniques entirely characterized the compounds. Single crystal studies investigated the crystal structure of ligand (1) and complexes (3,4). X-ray diffraction data analysis was used to confirm the enaminone form of 1. Also, 3 and 4 exhibited the classical three-legged piano stool structure with Ru(II) coordinated by the nitrogen and oxygen atoms of 1 and a chloride ligand as the legs and the η6-π-bound p-cymene ligand occupies the seat of the piano stool. The Ru(II) complexes have been studied as catalysts in the transfer hydrogenation of acetophenone and other various ketones in the presence of KOtBu. The catalytic conditions were optimized using different substrate/catalyst and base/catalyst ratios. We found that the complexes show good activities and up to 100 % selectivity. The best turnover frequency (1667 h−1) was found for 3 when using acetophenone as the substrate.

Organic-Inorganic Hybrid Silica Film with a TGBA* Structure.

Twisted grain boundary (TGB) phases exhibit highly frustrated and complex liquid crystal structures, and have attracted enormous interest because of their unique internal structure, textures and properties. However, among the few real concerns related to these interesting structures, applying them to prepare polymer-stabilized colored liquid crystal films has been challenging. Herein, the organic-inorganic hybrid silica (OIHS) films with a TGBA* structure were prepared using two organosilanes and one chiral additive under an acidic condition. The structural color of the films can be adjusted by varying the polycondensation temperature and the concentration of the chiral additive. A structurally colored pattern was prepared by the inject printing, which was suitably applied for decoration and anti-counterfeiting.

Synthesis, characterization and computational studies of the triangle shape complex of silver nitrate with 2-amino-1,3,4-thiadiazole

A new mononuclear salt-like silver(I) complex [AgL3]NO3 (Complex 1), which was readily fabricated from 2-amino-1,3,4-thiadiazole (L), is reported. Complex 1 was analyzed by elemental analysis, FT-IR and UV–vis spectroscopy, and single crystal X-ray diffraction. Intermolecular contacts for the cation [AgL3]+ in the crystal structure of Complex 1 were examined using the Hirshfeld surface analysis. The DFT-based calculations were additionally applied to reveal electronic features of Complex 1. The molecular structure of Complex 1 exhibits a mononuclear planar cation [AgL3]+ of the triangle shape with three ligands L being monocoordinated through thiadiazole the nitrogen atom, located at the third position. Two cations [AgL3]+, which, in turn, are stabilized by three NH⋯N hydrogen bonds, are stacked through a rich variety of noncovalent interactions formed by the thiadiazole π-system, yielding a supramolecular dimer {[AgL3]2}2+. These dimers are linked through Ag⋯Ag interactions with the formation of a 1D supramolecular cationic pillar {[AgL3]n}n+. A solution of Complex 1 in EtOH absorbs in the UV region due to intraligand transitions within L. Theoretical calculations revealed a strong electrophilic nature of the optimized structure of Complex 1.

Copper(II) and Zinc(II) complexes of new water-soluble Schiff base ligands and their antiproliferative properties towards mesothelioma cell line

In this work, three Schiff base ligands (HL1-HL3) containing a triphenyl phosphonium cation and their Cu(II) and Zn(II) complexes with the general formulae of [M(L)Cl2] were synthesized and their structures were characterized by spectroscopic and analytical methods. Crystal structure of complex [Zn(L1)Cl2] was determined. In the structure of the complex, each Zn(II) ion is four coordinated binding to phenolate oxygen and imine nitrogen atoms of the ligand L1 and two chloride atoms in approximately tetrahedral geometry. The equilibrium geometry of three Schiff base ligands (HL1-HL3) and their Cu(II) and Zn(II) complexes were calculated using the density functional theory (DFT/B3LYP) method with the 6–31++G(d,p) basis set for the C, H, Cl, N, O, P atoms and LANL2DZ for the I atom. Frontier molecular orbitals (HOMO, LUMO) analyses were conducted for the optimized geometries of the compounds, and chemical reactivity descriptors such as hardness, softness, electrophilicity, and electronegativity were examined. Additionally, the molecular electrostatic potential (MEP) of all compounds was modeled using DFT calculations. These calculations were thoroughly examined, and their implications were discussed. The ligands and their metal complexes were investigated for their DNA binding properties. The compounds showed comparable DNA binding properties to ethidium bromide (EB) and 5-fluorouracyl (5-Fu) with DNA binding constant (Kb) 1.5–6.25 × 105 M−1. The cytotoxic properties of the compounds towards HUVEC and H2452 (mesothelioma cell line) cells were investigated using an MTS assay. The IC50 values determined for HUVEC cells were found to range between 27.28 µg/mL ([Cu(L2)Cl2]) and 273.1 µg/mL ([Zn(L2)Cl2]), while in H2452 cells, they varied from 39.48 µg/mL ([Cu(L2)Cl2]) to 319.3 µg/mL ([Zn(L3)Cl2]). The compounds HL1, HL3, and [Zn(L3)Cl2] exhibited antioxidant activity at the highest concentration (750 µg/mL) only, while [Zn(L1)Cl2], HL2, [Zn(L2)Cl2], [Cu(L2)Cl2], and [Cu(L3)Cl2] showed antioxidant activity at 250 µg/mL.

Crystal structure and supra-molecular features of a host-guest inclusion complex based on A1/A2-hetero-difunctionalized pillar[5]arene.

A host-guest supra-molecular inclusion complex was obtained from the co-crystallization of A1/A2-bromo-but-oxy-hy-droxy difunctionalized pillar[5]arene (PilButBrOH) with adipo-nitrile (ADN), C47H53.18Br0.82O10·C6H8N2. The adipo-nitrile guest is stabilized within the electron-rich cavity of the pillar[5]arene host via multiple C-H⋯O and C-H⋯π inter-actions. Both functional groups on the macrocyclic rim are engaged in supra-molecular inter-actions with an adjacent inclusion complex via hydrogen-bonding (O-H⋯N or C-H⋯Br) inter-actions, resulting in the formation of a supra-molecular dimer in the crystal structure.

Synthesis of 2‐Pyridyl Based N(1)‐Substituted Thiosemicarbazonates of Nickel(II) as Bioactive Materials against MRSA, S. aureus, S. typhimurium 2, and K. pneumonia

AbstractIn this investigation, the bio‐activity and biosafe potential of thiosemicarbazonates of nickel(II) as well as that of ligands are described. Reactions of nickel(II) acetate with a series of thiosemicarbazones, {R1(py)C2=N3‐N2(H)‐C1(=S)‐NHR; R1=py, Me, H and Ph; R=H, Me, Et, Ph}, led to the loss of acidic hydrazinic N2(H) protons, and resulted in the formation of six‐coordinated complexes of stoichiometry, [Ni(N,N,S−L)2], where anionic N,N,S−L=py2tsc‐NHR, 1–4; apytsc‐NHR, 5–8; pytsc‐NHR, 9–12 and bpytsc‐NHR, 13–16. All these complexes have been characterized using analytical data, IR and UV‐visible spectroscopy and ESI‐mass spectrometry. The single crystal X‐ray crystal structure of several complexes {2(Me), 7(Et), 11(Et), 12(Ph), 13(H),14(Me) and 15(Et)} were also determined. Thio‐ligands coordinate to nickel(II) through pyridyl nitrogen‐N4, azomethine nitrogen‐N3 and thiolato sulfur atoms, resulting in the formation of homoleptic complexes with octahedral structures. Complexes 1–16 and uncoordinated thiosemicarbzones, were evaluated for their antimicrobial activity, in terms of ZOI, MIC, time kill assay and in vitro percent cell viability MTT assay, against clinical isolate methicillin‐resistant Staphylococcus aureus (MRSA), Staphylococcus aureus (MTCC740), Klebsiella pneumonia (MTCC109), Salmonella typhimurium (MTCC1251), and Candida albicans (MTCC227), a yeast. Both the ligands and their metal complexes exhibited moderate to high bioactivity, and were found to be biosafe with high cell viability, 88–92 %, in several cases.

Microstructures and corrosion behaviors under sodium chloride aqueous conditions of Co-free non-equiatomic Al0.32CrFeTi0.73(Ni1.50-xMox) (x=0, 0.23) high entropy alloys

High entropy alloys (HEAs) were prepared using a vacuum arc melting method. The effect of Mo partially substituting Ni on the crystal structure and corrosion behaviors was studied. The results show that the HEAs exhibited a multiphase complex crystal structure which was composed of a BCC matrix and several intermetallic phases. The HEAs showed good corrosion resistance despite multiphase heterogeneity. But cyclic polarization showed that the HEAs were susceptible to pitting corrosion. Selective corrosion of Cr-depleted phases after polarization tests was attributed to the galvanic corrosion between Cr-depleted and Cr-rich phases. The spontaneous passive films on the HEAs surface were characterized by p-type semiconductor. Existence of Mo element of the HEAs accelerated passivation reaction kinetics, improved the stability of passive film, accordingly, acquired better general and pitting corrosion resistance.

Long-Chain Molecular Crystals Antimony(III) Alkanethiolates Sb(SCnH2n+1)3 (n ≥ 12): Synthesis, Crystal and Electronic Structures, and Supramolecular Self-Assembly via Secondary Interactions.

Currently, there is not much success in solving the molecular and crystal structures of long-chain metal alkanethiolate complexes [M(SCnH2n+1)m] at the atomic level. Taking Sb(SC16H33)3 (1) as an example, we herein disclose the structural characteristics of long-chain trivalent antimony(III) alkanethiolates Sb(SCnH2n+1)3 (n ≥ 12) by single-crystal X-ray crystallography. Specifically, the Sb atom is three-coordinated by alkanethiolate ligands and a slightly distorted triangular pyramid SbS3 core is formed owing to the unique intramolecular stereochemistry of three alkyl chains, namely, two of them almost parallel aligning and the third chain extending alone around the SbS3 core. We further determine the conformation, spatial orientation and packing density of alkyl chains in 1 along with a comparison to those in other long-chain crystalline systems, and reveal the roles of intermolecular van der Waals and Sb···S secondary interactions in molecular self-assembly, which enables 1 to be a layer-structured molecular crystal with a monoclinic P21/c unit cell. The band structures and the atomic orbital contributions to the valence band maximum and conduction band minimum for 1 have also been evaluated by DFT calculations and rationally correlated with its optical absorption property. This study will help understand and discover new structures and structure-property relations of long-chain chemical systems.

A second life for the crystallographic structure of Berenil-dodecanucleotide complex: a computational revisitation thirty years after its publication

AbstractThis study revisits the pioneering work of Professor Neidle, and co-workers, on the crystal structure of complexes formed between groove binders and DNA sequences. The original research revealed a DNA-ligand complex consisting of a dodecanucleotide bound with Berenil [1,3-bis(4′-amidinophenyl)-triazene] an anti-trypanocidal drug. This article aims to delve deeper into the structural dynamics of this system, showcasing the role played by water molecules in stabilizing the interaction between the ligand and the DNA. With this work, we reevaluate the findings from the original crystallographic study by employing modern molecular dynamics techniques, including Supervised Molecular Dynamics (SuMD) for generating binding trajectories, Thermal Titration Molecular Dynamics for assessing unbinding events, and AquaMMapS to identify regions occupied by stationary water molecules. The study addresses a minor and a major groove binding mode and assesses their strength and specificity using TTMD simulations, generating unbinding trajectories. This comprehensive approach integrates the understanding of the interaction of this DNA-ligand complex, which originated with the valuable work of Professor Neidle, resulting in an in-depth insight into the pivotal role of water molecules with this DNA, a behavior detected and extendable even to other nucleic acid complexes.

Synchrotron scanning transmission x-ray spectro-microscopy (STXM) characterisation of β-SiC nanowhisker AZ91 magnesium alloy nanocomposites

β-SiC nanoparticles are one of the most common reinforcements in Mg-Al alloy matrix nanocomposites (MgMNCs). The interfacial interactions between β-SiC and the alloy matrix are complex due to the occurrence of new phases and the fine scale of the 3D architecture. This study aims to explore the feasibility of using synchrotron Scanning Transmission X-ray spectro-Microscopy (STXM) to investigate such interfacial interactions and acquire reference X-ray Absorption Spectroscopy (XAS) data for some common interphase crystals present within the composites, which are not readily available. Throughout this study, a reliable procedure for collecting STXM data on samples derived from MgMNCs was developed, and reference XAS spectra for α-Mg, β-Mg17Al12, T2-Al2MgC2, Mg2Si and MgO present in MgMNCs were collected. The accessibility of STXM and spatially resolved XAS spectrum is not only useful for nanocomposite alloy research but applicable widely across the magnesium alloy research community when identifying and quantifying the phases with complex crystal structures and oxide states.

DFT-based investigation of polyetherketoneketone materials for surface modification for dental implants

BackgroundPolyetherketoneketone (PEKK) is a high-performance thermoplastic polymer with unique structural and mechanical properties that make it a promising candidate for surface modification of dental implants. This study was conducted to investigate the feasibility of PEKK for this purpose using the Cambridge Serial Total Energy Package (CASTEP) code based on density functional theory (DFT).MethodsThis study examined the ground state energy, structural properties, thermodynamic behavior, cohesive energy, refractive index, stress analysis, mechanical properties, and anisotropic behavior of PEKK.ResultsThis study found that PEKK has a complex crystal structure with an orthorhombic unit cell shape, triclinic lattice type, and a centered structure. It also has a 2D layered structure owing to the presence of carbonyl groups, which provides a large surface area for interaction with biological tissues. Thermodynamic analysis showed that PEKK exhibited bond elongation and structural changes at 380 °C, indicating thermal degradation. The cohesive energy of PEKK was calculated to be – 440 eV, indicating its stability and structural integrity. PEKK has a complex refractive index, with real and imaginary components that affect its optical properties. Stress analysis showed that PEKK is resistant to shear deformation and has high hydrostatic stress, which contributes to its stability and biocompatibility.ConclusionThe mechanical properties of PEKK, including its high stiffness, resistance to volume change under pressure, and ability to accommodate natural movements, make it suitable for surface modification of dental implants.

Exploring the Impact of Protein Chain Selection in Binding Energy Calculations with DFT.

Calculation of binding free energies between a protein and a ligand are highly desired for computer-aided drug design. Here we approximate the binding energies of ABL1, an enzyme which is the target for drugs used in the treatment of chronic myeloid leukaemia, with minimal models and density functional theory (DFT). Starting from the crystal structures of protein-drug complexes, we estimated the binding free energies having used all available individual molecules (protein chains) within each structure, not only a single one as commonly used, in order to see if the choice of the protein chain is important in such calculations. Differences were observed between chains in the same file. Energy decomposition analysis (EDA) revealed that the most important factors for binding were exchange, repulsion and electrostatics. The desolvation term varied dramatically between the inhibitors (between 4.2 and 92.3 kcal/mol). All functionals showed similar patterns in the EDA and in discriminating between the ligands. Non-covalent interactions (NCI) analysis was used to further explain the differences between protein chains and functionals. Overall, it is shown that small minimal models of a drug binding site can be useful to infer on the suitability of an initial crystal structure for further analysis such as EDA.

The First Crystal Structure of an Anti-Geometric Homoleptic Zinc Complex from an Unsymmetric Curcuminoid Ligand

Curcuminoids are widely studied due to their well-recognized therapeutic properties. These molecules are often derivatized with metals, producing their corresponding homoleptic metal complexes. Numerous crystal structures of homoleptic symmetric curcuminoids with physiologically essential metals are known, although the literature lacks reports of homoleptic metal complexes of unsymmetric curcuminoids (or hemi-curcuminoids) as ligands. Three unknowns must be solved when an unsymmetric curcuminoid ligand is reacted with a metal ion: (a) the degree of coordination (MLn); (b) the spatial geometry; and (c) the conformational nature (syn or anti) of the complex. Herein, we report the structure of the anti-isomer of the Zn complex of the hemi-curcuminoid 5-hydroxy-1-(4-methoxyphenyl)hexa-1,4-dien-3-one. While the NMR shows only one set of signals for this homoleptic complex, the unambiguous stereochemistry was established through single-crystal X-ray diffractometry, revealing an anti-hexacoordinated octahedral ML2 structure.

(Ba0.5Sr0.5)(Ti0.25Zr0.25Hf0.25Sn0.25)O3: A novel thermal barrier material with low thermal conductivity and excellent resistance to CMAS corrosion

High entropy ceramics are considered as promising materials for thermal barrier coatings due to phonon scattering caused by lattice distortion. In this study, perovskite high-entropy ceramics (Ba0.5Sr0.5)(Ti0.25Zr0.25Hf0.25Sn0.25)O3 (BSTZHS) were successfully prepared by dramatically increasing the conformational entropy of ceramics with complex crystal structures. The results showed that the sample exhibits a single-phase perovskite crystal structure with a dense surface, each element of the sample was uniformly distributed. Moreover, the thermal conductivity of (Ba0.5Sr0.5)(Ti0.25Zr0.25Hf0.25Sn0.25)O3 decreased significantly compared to SrZrO3 and BaZrO3 (the minimum thermal conductivity is 1.37 W/(m·K) at 273–1273 K). This study also identified descriptors for predicting the decrease in thermal conductivity of perovskite high-entropy ceramics. As well, the samples not only exhibit outstanding mechanical properties (Young’s modulus E = 255.7 ± 8.6 GPa、flexural strength Fb = 142.1 ± 4.8 MPa), but also good resistance to CMAS corrosion. Various results support that (Ba0.5Sr0.5)(Ti0.25Zr0.25Hf0.25Sn0.25)O3 is potential to be used for thermal barrier coatings.

Enhancing the thermoelectric performance of Sr0.6La0.4Nb2O6-δ-based ceramics through composite effects

Donor-doped SrNb2O6-based materials are regarded as highly promising candidates for high-temperature thermoelectric applications. The Sr0.6La0.4Nb2O6-δ/x wt% Ti (x = 1, 5, 10, 15) composite ceramics thermoelectric materials were prepared and the mechanism for enhancing their thermoelectric properties was investigated. The experimental results demonstrate that during sintering, nano-additive titanium powder undergoes oxidation to form TiO2. The inclusion of a secondary phase ultimately leads to successful reduction in electrical resistivity within the composite oxides. Due to crystal defects, complex structure and phonon scattering at grain boundaries, the samples consistently exhibit low thermal conductivity values below 3.0 W m−1K−1. Among them, the sample doped with 10 wt% Ti shows the highest PF value (470.0 μW/mK2 at 1073 K), demonstrating a significant increase in power factor of 280 % compared to Sr0.6La0.4Nb2O6 without the Ti composite. Consequently, the Sr0.6La0.4Nb2O6-δ/10 wt% Ti composite material achieved a maximum ZT value of 0.20, representing a fifty-three percent enhancement compared to the undoped sample.

Pillar[5]arene-Based Ion-Pair Recognition for Encapsulation of a Stilbazolium-Type Dye with Enhanced Photophysical Properties and Nonlinear Optical Activity.

Constructing organic composite materials through molecular recognition has emerged as an important theme in materials science. Here we report an ion-pair recognition system involving the use of a propoxylated pillar[5]arene (PrP5) to modulate the solid-state photophysical properties of dye trans-4'-(dimethylamino)-N-methyl-4-stilbazolium hexafluorophosphate (DMASP). Single crystal X-ray diffraction analysis reveals that the dye guest DMASP is encapsulated by PrP5 to form a 2 : 1 host-guest complex 2PrP5⸧DMASP in the crystalline state. The macrocyclic skeleton of PrP5 imposes restrictions on the intramolecular motions of the dye guest, leading to a significant enhancement of its fluorescence emission. Additionally, within the 2PrP5⸧DMASP complex crystal structure, DMASP molecules are found to display two possible opposite orientations in the one-dimensional channels formed by PrP5 molecules. This arrangement is believed to alter the overall solid-state packing structure of DMASP, thereby activating its nonlinear optical activity. This work not only reports a novel ion-pair molecular recognition system based on pillararenes but also provides valuable insights into the modulation of the crystalline state photophysical properties of organic dyes via cocrystal engineering.

The Implication of Fragment-centric Mapping Strategy to Explore the First Selective Inhibitor Against Target Protein

Introduction: Identification of the first selective inhibitor, also called “hit molecules, " is crucial for developing drugs against a protein target. However, the crystal structures of protein-ligand complexes are usually not resolved in time due to the process's time-consuming and costly nature. However, it does not prevent scientists from understanding the binding modes’ urgent advantages and drawbacks of protein-ligand interaction to guide the optimization of hit molecules. Methods: Here, we have developed a pocket-centric computational strategy to facilitate a comprehensive understanding of the hit molecules against the protein target. Results: The results show that the pocket-centered mapping method not only allows for accurate prediction of the native docking pose and in-depth analysis of the binding mode but also has the potential of rapidly identifying partially unoccupied, unutilized, but targetable pockets to afford optimized hit molecules. We tested the strategy on the first selective inhibitor, epigallocatechin gallate (EGCG), against human arylacetamide deacetylase (AADAC). Molecular dynamics simulation and MM/PBSA binding energy calculation are used to verify the efficacy of the strategy. Conclusion: The results show that the pocket-centered mapping method not only allows for accurate prediction of the native docking pose and in-depth analysis of the binding mode but also has the potential of rapidly identifying partially unoccupied, unutilized, but targetable pockets to afford optimized hit molecules.