Interakce heteroboranů sbiomolekkulami: kvantově chemická studie

Charles University in Prague Faculty of Science Department of Physical and Macromolecular Chemistry Interaction of heteroboranes with biomolecules: Accurate quantum chemical study Doctoral Thesis Abstract RNDr. Jindřich Fanfrlík Advisor: Prof. Ing. Pavel Hobza, DrSc. Institute of Organic Chemistry and Biochemistry, AS CR Center for Biomolecules and Complex Molecular Systems Prague 2008 Univerzita Karlova v Praze Přírodovĕdecká Fakulta Katedra fyzikální a makromolekulární chemie Interakce heteroboranů s biomolekulami: kvantovĕ chemická studie Autoreferát disertační práce RNDr. Jindřich Fanfrlík Školitel: Prof. Ing. Pavel Hobza, DrSc. Ústav organické chemie and biochemie, AV ČR Centrum biomolekul a komplexních molekulových systémů Praha 2008 Introduction The world wide epidemic of AIDS is caused by two species of the human immunodeficiency virus (HIV-1 and HIV-2). Its 9200-bases-long RNA genome contains three main genes: gag, pol and env. The enzymes located within the pol gene (protease PR and reverse transcriptase RT) have become major targets for drug discovery, e.g. RT inhibitor Tenofovir disoproxil fumarate (DF) discovered by A. Holy at UOCHB in Prague and manufactured by Gilead Sciences and also already ten HIV-1 PR inhibitors (PIs) have been approved for use in the clinics: The evolution of drug...Charles University in Prague Faculty of Science Department of Physical and Macromolecular Chemistry Interaction of heteroboranes with biomolecules: Accurate quantum chemical study Doctoral Thesis Abstract RNDr. Jindřich Fanfrlík Advisor: Prof. Ing. Pavel Hobza, DrSc. Institute of Organic Chemistry and Biochemistry, AS CR Center for Biomolecules and Complex Molecular Systems Prague 2008 Univerzita Karlova v Praze Přírodovĕdecká Fakulta Katedra fyzikální a makromolekulární chemie Interakce heteroboranů s biomolekulami: kvantovĕ chemická studie Autoreferát disertační práce RNDr. Jindřich Fanfrlík Školitel: Prof. Ing. Pavel Hobza, DrSc. Ústav organické chemie and biochemie, AV ČR Centrum biomolekul a komplexních molekulových systémů Praha 2008 Introduction The world wide epidemic of AIDS is caused by two species of the human immunodeficiency virus (HIV-1 and HIV-2). Its 9200-bases-long RNA genome contains three main genes: gag, pol and env. The enzymes located within the pol gene (protease PR and reverse transcriptase RT) have become major targets for drug discovery, e.g. RT inhibitor Tenofovir disoproxil fumarate (DF) discovered by A. Holy at UOCHB in Prague and manufactured by Gilead Sciences and also already ten HIV-1 PR inhibitors (PIs) have been approved for use in the clinics: The evolution of drug...Department of Physical and Macromolecular ChemistryKatedra fyzikální a makromol. chemieFaculty of SciencePřírodovědecká fakult

A novel stibacarbaborane cluster with adjacent antimony atoms exhibiting unique pnictogen bond formation that dominates its crystal packing

We have prepared nido-7,8,9,11-Sb2C2B7H9, the first cluster with simultaneous Sb-B, Sb-C and Sb-Sb atom pairs with interatomic separations with magnitudes that approach the respective sums of covalent radii. However, the length of the Sb-Sb separation in this cluster is slightly less than the sum of the covalent radii. Quantum chemical analysis has revealed that the crystal packing of nido-7,8,9,11-Sb2C2B7H9 is predominantly dictated by pnictogen (Pn) bonding, an unconventional σ-hole interaction. Indeed, the interaction energy of a very strong Sb2⋯H-B Pn-bond in the nido-7,8,9,11-Sb2C2B7H9 dimer exceeds -6.0 kcal mol-1. This is a very large value and is comparable to the strengths of known Pn-bonds in Cl3Pn⋯π complexes (Pn = As, Sb)

Face-Fusion of Icosahedral Boron Hydride Increases Affinity to γ‐Cyclodextrin: closo,closo‐[B₂₁H₁₈]⁻ as an Anion with Very Low Free Energy of Dehydration

[Abstract] The supramolecular recognition of closo,closo‐[B₂₁H₁₈]⁻ by cyclodextrins (CDs) has been studied in aqueous solution by isothermal titration calorimetry and nuclear magnetic resonance spectroscopy. These solution studies follow up on previous mass‐spectrometric measurements and computations, which indicated the formation and stability of CD ⋅ B₂₁H₁₈⁻ complexes in the gas phase. The thermodynamic signature of solution‐phase binding is exceptional, the association constant for the γ‐CD complex with B₂₁H₁₈⁻ reaches 1.8×10⁶ M⁻¹, which is on the same order of magnitude as the so far highest observed value for the complex between γ‐CD and a metallacarborane. The nature of the intermolecular interaction is also examined by quantum‐mechanical computational protocols. These suggest that the desolvation penalty, which is particularly low for the B₂₁H₁₈⁻ anion, is the decisive factor for its high binding strength. The results further suggest that the elliptical macropolyhedral boron hydride is another example of a CD binder, whose extraordinary binding affinity is driven by the chaotropic effect, which describes the intrinsic affinity of large polarizable and weakly solvated chaotropic anions to hydrophobic cavities and surfaces in aqueous solution.K.I.A. and W.M.N. are grateful to the DFG for grant NA-686/8 within the priority program SPP 1807 “Control of London Dispersion Interactions in Molecular Chemistry”. J.H., J.F., and D.H. thank the Czech Science Foundation (grant number 17-08045S) and M.I.F.P., M.C.L, and J.A.S.L. thank the regional government Xunta de Galicia for financial support (Project Grupo Potencial Crecemento -GPC- ED431B 2017/59). J.M.O.-E. acknowledges financial support from the Spanish MICINN through project CTQ2018-094644-B-C22German Research Foundation; NA‐686/8Czech Science Foundation; 17‐08045SXunta de Galicia; ED431B 2017/5

Nuclear magnetic shielding of monoboranes : calculation and assessment of 11B NMR chemical shifts in planar BX3 and in tetrahedral [BX4]- systems

The financial support of the Czech Science Foundation (project No. 17-08045S) is gratefully acknowledged.11B NMR chemical shifts of tricoordinated BX3 and tetracoordinated BX4- compounds (X = H, CH3, F, Cl, Br, I, OH, SH, NH2, and CH=CH2) were computed and the shielding tensors were explored not only within the nonrelativistic GIAO approach but also by applying both relativistic ZORA computations including spin-orbit coupling as well as by employing scalar nonrelativistic ZORA computations (BP86 level of density functional theory). The contributions of the spin-orbit coupling to the overall shieldings are decisive for X = Br and I in both series. No relationship was found between the 2p orbital occupancies or 1/∆E (difference between LUMO and suitably occupied MO that can be coupled with LUMO) with the shielding tensors (or their principal values) in the BX3 series. However, a multidimensional statistical approach known as factor analysis (frequently used in chemometrics) revealed that three factors account for 92 % of the cumulative proportion of total variance. The main components of the first factor are occupancies in the 2px and 2py orbitals and 1/∆E, the second factor is mainly the occupancy in the 2pz orbital and the inductive substituent parameters by Taft and, finally, the third factor consists exclusively (99.3 %) of the electrostatic potentials (Vmax), which is directly related to the so-called π-hole magnitudes.PostprintPeer reviewe

Interaction of heteroboranes with biomolecules: Accurate quantum chemical study

Charles University in Prague Faculty of Science Department of Physical and Macromolecular Chemistry Interaction of heteroboranes with biomolecules: Accurate quantum chemical study Doctoral Thesis Abstract RNDr. Jindřich Fanfrlík Advisor: Prof. Ing. Pavel Hobza, DrSc. Institute of Organic Chemistry and Biochemistry, AS CR Center for Biomolecules and Complex Molecular Systems Prague 2008 Univerzita Karlova v Praze Přírodovĕdecká Fakulta Katedra fyzikální a makromolekulární chemie Interakce heteroboranů s biomolekulami: kvantovĕ chemická studie Autoreferát disertační práce RNDr. Jindřich Fanfrlík Školitel: Prof. Ing. Pavel Hobza, DrSc. Ústav organické chemie and biochemie, AV ČR Centrum biomolekul a komplexních molekulových systémů Praha 2008 Introduction The world wide epidemic of AIDS is caused by two species of the human immunodeficiency virus (HIV-1 and HIV-2). Its 9200-bases-long RNA genome contains three main genes: gag, pol and env. The enzymes located within the pol gene (protease PR and reverse transcriptase RT) have become major targets for drug discovery, e.g. RT inhibitor Tenofovir disoproxil fumarate (DF) discovered by A. Holy at UOCHB in Prague and manufactured by Gilead Sciences and also already ten HIV-1 PR inhibitors (PIs) have been approved for use in the clinics: The evolution of drug..

Dihalogen and Pnictogen Bonding in Crystalline Icosahedral Phosphaboranes

Noncovalent interactions in the single crystal of 3,6-Cl2-closo-1,2-P2B10H8 and in the crystal of closo-1,7-P2B10Cl10•toluene were analyzed by means of quantum chemical computations. The crystal packing in the second crystal was dominated by numerous B-Cl···Cl-B dihalogen and strong B-P···π pnictogen bonds, the latter of which were characterized by a small length of 3.08 Å and a large interaction energy value, exceeding −10 kcal mol−1

Chalcogen Bonding due to the Exo-Substitution of Icosahedral Dicarbaborane

Chalcogen atoms are a class of substituents capable of generating inner and outer derivatives of boron clusters. It is well known that chalcogenated boron clusters can form strong σ-hole interactions when a chalcogen atom is a part of an icosahedron. This paper studies σ-hole interactions of dicarbaboranes with two exopolyhedral chalcogen atoms bonded to carbon vertices. Specifically, a computational investigation has been carried out on the co-crystal of (1,2-C2B10H10)2Se4•toluene and a single crystal of (1,2-C2B10H10)2Te4

SQM2.20: Semiempirical quantum-mechanical scoring function yields DFT-quality protein–ligand binding affinity predictions in minutes

Accurate estimation of protein–ligand binding affinity is the cornerstone of computer-aided drug design. We present a universal physics-based scoring function, named SQM2.20, addressing key terms of binding free energy using semiempirical quantum-mechanical computational methods. SQM2.20 incorporates the latest methodological advances while remaining computationally efficient even for systems with thousands of atoms. To validate it rigorously, we have compiled and made available the PL-REX benchmark dataset consisting of high-resolution crystal structures and reliable experimental affinities for ten diverse protein targets. Comparative assessments demonstrate that SQM2.20 outperforms other scoring methods and reaches a level of accuracy similar to much more expensive DFT calculations. In the PL-REX dataset, it achieves excellent correlation with experimental data (average R^2 = 0.69) and exhibits consistent performance across all targets. In contrast to DFT, SQM2.20 provides affinity predictions in minutes, making it suitable for practical applications in hit identification or lead optimization

Hydration Gibbs Energies of Nucleic Acid Bases Determined by Gibbs Energy Perturbation, Continuous and Hybrid Approaches

The hydration Gibbs energies of adenine, cytosine, guanine, thymine, uracil and isoguanine are determined by the molecular dynamics-thermodynamic integration method (MD-TI) and using continuous COSMO and hybrid models. The role of solvents in the COSMO model is described by permittivity and by combining the permittivity and specific hydration of single water molecules placed on the energetically most probable position in the hybrid model. The hybrid model describes hydration similarly to the COSMO model; both the continuous methods are in good agreement with the MD-TI method. Differences are small and the use of both models can be recommended

SQM2.20: Semiempirical quantum-mechanical scoring function yields DFT-quality protein–ligand binding affinity predictions in minutes

Abstract Accurate estimation of protein–ligand binding affinity is the cornerstone of computer-aided drug design. We present a universal physics-based scoring function, named SQM2.20, addressing key terms of binding free energy using semiempirical quantum-mechanical computational methods. SQM2.20 incorporates the latest methodological advances while remaining computationally efficient even for systems with thousands of atoms. To validate it rigorously, we have compiled and made available the PL-REX benchmark dataset consisting of high-resolution crystal structures and reliable experimental affinities for ten diverse protein targets. Comparative assessments demonstrate that SQM2.20 outperforms other scoring methods and reaches a level of accuracy similar to much more expensive DFT calculations. In the PL-REX dataset, it achieves excellent correlation with experimental data (average R 2 = 0.69) and exhibits consistent performance across all targets. In contrast to DFT, SQM2.20 provides affinity predictions in minutes, making it suitable for practical applications in hit identification or lead optimization