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Yunxiang Lu

Bio: Yunxiang Lu is an academic researcher from East China University of Science and Technology. The author has contributed to research in topics: Halogen bond & Hydrogen bond. The author has an hindex of 18, co-authored 64 publications receiving 1440 citations.


Papers
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Journal ArticleDOI
TL;DR: It is suggested that albeit halogenation is a valuable approach for improving ligand bioactivity, more attention should be paid in the future to the application of the halogen bond for ligand ADME/T property optimization.
Abstract: Halogen bond has attracted a great deal of attention in the past years for hit-to-lead-to-candidate optimization aiming at improving drug-target binding affinity. In general, heavy organohalogens (i.e., organochlorines, organobromines, and organoiodines) are capable of forming halogen bonds while organofluorines are not. In order to explore the possible roles that halogen bonds could play beyond improving binding affinity, we performed a detailed database survey and quantum chemistry calculation with close attention paid to (1) the change of the ratio of heavy organohalogens to organofluorines along the drug discovery and development process and (2) the halogen bonds between organohalogens and nonbiopolymers or nontarget biopolymers. Our database survey revealed that (1) an obviously increasing trend of the ratio of heavy organohalogens to organofluorines was observed along the drug discovery and development process, illustrating that more organofluorines are worn and eliminated than heavy organohalogens ...

261 citations

Journal ArticleDOI
TL;DR: This review article covers the recent advances relevant to halogen bonding in drug discovery and biological design over the past decade, including database survey of this interaction in protein–ligand complexes, molecular mechanical investigations of halogen bonded ligands in drugiscovery and applications ofThis interaction in the development of Halogenated ligands as inhibitors and drugs for protein kinases, serine protease factor Xa, HIV reverse transcriptase and so on.
Abstract: Introduction: A large number of drugs and drug candidates in clinical development contain halogen substituents. For a long time, only the steric and lipophilic contributions of halogens were considered when trying to exploit their effects on ligand binding. However, the ability of halogens to form stabilizing interactions, such as halogen bonding, hydrogen bonding and multipolar interactions, in biomolecular systems was revealed recently. Halogen bonding, the non-covalent interaction in which covalently bound halogens interact with Lewis bases, has now been utilized in the context of rational drug design. Areas covered: The purpose of this review is to show how halogen bonding could be used in drug design, and in particular, to stimulate researchers to apply halogen bonding in lead optimization. This review article covers the recent advances relevant to halogen bonding in drug discovery and biological design over the past decade, including database survey of this interaction in protein–ligand complexes, m...

237 citations

Journal ArticleDOI
TL;DR: X-ray crystal structures verified the existence of the predicted halogen bonds, demonstrating that the halogen bond is an applicable tool in drug design and should be routinely considered in lead optimization.
Abstract: For proof-of-concept of halogen bonding in drug design, a series of halogenated compounds were designed based on a lead structure as new inhibitors of phosphodiesterase type 5. Bioassay results revealed a good correlation between the measured bioactivity and the calculated halogen bond energy. Our X-ray crystal structures verified the existence of the predicted halogen bonds, demonstrating that the halogen bond is an applicable tool in drug design and should be routinely considered in lead optimization.

105 citations

Journal ArticleDOI
TL;DR: Fundamental characteristics of halogen bonding in media are established, which would be very helpful for applying this noncovalent interaction in medicinal chemistry and material design.
Abstract: A systematic study of halogen bonding interactions in gas phase and in solution was carried out by means of quantum chemical DFT/B3LYP method Three solvents with different polarities (chloroform, acetone, and water) were selected, and solvation effects were considered using the polarized continuum model (PCM) For charged halogen-bonded complexes, the strength of the interactions tends to significantly weaken in solution, with a concomitant elongation of intermolecular distances For neutral systems, halogen bond distances are shown to shorten and the interaction energies change slightly Computations also reveal that in the gas phase the binding affinities decrease in the order Cl(-) > Br(-) > I(-), while in solution the energy gaps of binding appear limited for the three halide anions According to free energy results, many systems under investigation are stable in solution Particularly, calculated free energies of formation of the complexes correlate well with halogen-bonding association constants determined experimentally The differences of the effects of solvent upon halogen and hydrogen bonding were also elucidated This study can establish fundamental characteristics of halogen bonding in media, which would be very helpful for applying this noncovalent interaction in medicinal chemistry and material design

104 citations

Journal ArticleDOI
TL;DR: 1,4-diiodo-perfluorobenzene, a very effective building block for crystal engineering based on halogen bonding, is selected in this work both as electron-deficient π aromatic ring and as halogen bond donor.
Abstract: Energetic effects between halogen bonds and anion-π or lone pair-π interactions have been investigated by means of ab initio MP2 calculations. 1,4-diiodo-perfluorobenzene, a very effective building block for crystal engineering based on halogen bonding, is selected in this work both as electron-deficient π aromatic ring and as halogen bond donor. Additive and diminutive effects are observed when halogen bonds and anion-π/lone pair-π interactions coexist in the same complex, which can be ascribed to the same direction of charge transfer for the two interactions. These effects have been analyzed in detail by the structural, energetic, and AIM properties of the complexes. Finally, experimental evidence of the combination of the interactions has been obtained from the Cambridge Structural Database.

76 citations


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01 May 1993
TL;DR: Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems.
Abstract: Three parallel algorithms for classical molecular dynamics are presented. The first assigns each processor a fixed subset of atoms; the second assigns each a fixed subset of inter-atomic forces to compute; the third assigns each a fixed spatial region. The algorithms are suitable for molecular dynamics models which can be difficult to parallelize efficiently—those with short-range forces where the neighbors of each atom change rapidly. They can be implemented on any distributed-memory parallel machine which allows for message-passing of data between independently executing processors. The algorithms are tested on a standard Lennard-Jones benchmark problem for system sizes ranging from 500 to 100,000,000 atoms on several parallel supercomputers--the nCUBE 2, Intel iPSC/860 and Paragon, and Cray T3D. Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems. For large problems, the spatial algorithm achieves parallel efficiencies of 90% and a 1840-node Intel Paragon performs up to 165 faster than a single Cray C9O processor. Trade-offs between the three algorithms and guidelines for adapting them to more complex molecular dynamics simulations are also discussed.

29,323 citations

Journal ArticleDOI
TL;DR: The specific advantages brought up by a design based on the use of the halogen bond will be demonstrated in quite different fields spanning from material sciences to biomolecular recognition and drug design.
Abstract: The halogen bond occurs when there is evidence of a net attractive interaction between an electrophilic region associated with a halogen atom in a molecular entity and a nucleophilic region in another, or the same, molecular entity. In this fairly extensive review, after a brief history of the interaction, we will provide the reader with a snapshot of where the research on the halogen bond is now, and, perhaps, where it is going. The specific advantages brought up by a design based on the use of the halogen bond will be demonstrated in quite different fields spanning from material sciences to biomolecular recognition and drug design.

2,582 citations

Journal ArticleDOI
TL;DR: A σ-hole bond is a noncovalent interaction between a covalently-bonded atom of Groups IV-VII and a negative site, e.g. a lone pair of a Lewis base or an anion.
Abstract: A σ-hole bond is a noncovalent interaction between a covalently-bonded atom of Groups IV–VII and a negative site, e.g. a lone pair of a Lewis base or an anion. It involves a region of positive electrostatic potential, labeled a σ-hole, on the extension of one of the covalent bonds to the atom. The σ-hole is due to the anisotropy of the atom's charge distribution. Halogen bonding is a subset of σ-hole interactions. Their features and properties can be fully explained in terms of electrostatics and polarization plus dispersion. The strengths of the interactions generally correlate well with the magnitudes of the positive and negative electrostatic potentials of the σ-hole and the negative site. In certain instances, however, polarizabilities must be taken into account explicitly, as the polarization of the negative site reaches a level that can be viewed as a degree of dative sharing (coordinate covalence). In the gas phase, σ-hole interactions with neutral bases are often thermodynamically unfavorable due to the relatively large entropy loss upon complex formation.

1,294 citations

Journal ArticleDOI
TL;DR: The theoretical background defining its strength and directionality, a systematic analysis of its occurrence and interaction geometries in protein-ligand complexes, and recent examples where halogen bonding has been successfully harnessed for lead identification and optimization are provided.
Abstract: Halogen bonding has been known in material science for decades, but until recently, halogen bonds in protein–ligand interactions were largely the result of serendipitous discovery rather than rational design. In this Perspective, we provide insights into the phenomenon of halogen bonding, with special focus on its role in drug discovery. We summarize the theoretical background defining its strength and directionality, provide a systematic analysis of its occurrence and interaction geometries in protein–ligand complexes, and give recent examples where halogen bonding has been successfully harnessed for lead identification and optimization. In light of these data, we discuss the potential and limitations of exploiting halogen bonds for molecular recognition and rational drug design.

934 citations