Why 1,2‑quinone derivatives are more stable than their 2,3‑analogues?

In this work, we have studied the relative stability of 1,2- and 2,3-quinones. While 1,2-quinones have a closed-shell singlet ground state, the ground state for the studied 2,3-isomers is open-shell singlet, except for 2,3-naphthaquinone that has a closed-shell singlet ground state. In all cases, 1,2-quinones are more stable than their 2,3-counterparts. We analyzed the reasons for the higher stability of the 1,2-isomers through energy decomposition analysis in the framework of Kohn–Sham molecular orbital theory. The results showed that we have to trace the origin of 1,2-quinones’ enhanced stability to the more efficient bonding in the π-electron system due to more favorable overlap between the SOMOπ of the ·C4n−2H2n–CH·· and ··CH–CO–CO· fragments in the 1,2-arrangement. Furthermore, whereas 1,2-quinones present a constant trend with their elongation for all analyzed properties (geometric, energetic, and electronic), 2,3-quinone derivatives present a substantial breaking in monotonicity.European Union in the framework of European Social Fund through the Warsaw University of Technology Development Programme. O.A. S., H. S. and T.M. K

Mechanism of biomolecular recognition of trimethyllysine by the fluorinated aromatic cage of KDM5A PHD3 finger

The understanding of biomolecular recognition of posttranslationally modified histone proteins is centrally important to the histone code hypothesis. Despite extensive binding and structural studies on the readout of histones, the molecular language by which posttranslational modifications on histone proteins are read remains poorly understood. Here we report physical-organic chemistry studies on the recognition of the positively charged trimethyllysine by the electron-rich aromatic cage containing PHD3 finger of KDM5A. The aromatic character of two tryptophan residues that solely constitute the aromatic cage of KDM5A was fine-tuned by the incorporation of fluorine substituents. Our thermodynamic analyses reveal that the wild-type and fluorinated KDM5A PHD3 fingers associate equally well with trimethyllysine. This work demonstrates that the biomolecular recognition of trimethyllysine by fluorinated aromatic cages is associated with weaker cation-π interactions that are compensated by the energetically more favourable trimethyllysine-mediated release of high-energy water molecules that occupy the aromatic cage

Quantum mechanical studies of lincosamides

Lincosamides are a class of antibiotics used both in clinical and veterinary practice for a wide range of pathogens. This group of drugs inhibits the activity of the bacterial ribosome by binding to the 23S RNA of the large ribosomal subunit and blocking protein synthesis. Currently, three X-ray structures of the ribosome in complex with clindamycin are available in the Protein Data Bank, which reveal that there are two distinct conformations of the pyrrolidinyl propyl group of the bound clindamycin. In this work, we used quantum mechanical methods to investigate the probable conformations of clindamycin in order to explain the two binding modes in the ribosomal 23S RNA. We studied three lincosamide antibiotics: clindamycin, lincomycin, and pirlimycin at the B3LYP level with the 6-31G** basis set. The focus of our work was to connect the conformational landscape and electron densities of the two clindamycin conformers found experimentally with their physicochemical properties. For both functional conformers, we applied natural bond orbital (NBO) analysis and the atoms in molecules (AIM) theory, and calculated the NMR parameters. Based on the results obtained, we were able to show that the structure with the intramolecular hydrogen bond C=O…H–O is the most stable conformer of clindamycin. The charge transfer between the pyrrolidine-derivative ring and the six-atom sugar (methylthiolincosamide), which are linked via an amide bond, was found to be the dominant factor influencing the high stability of this conformer

Optoelectronic and Excitonic Properties of Oligoacenes: Substantial Improvements from Range-Separated Time-Dependent Density Functional Theory

The optoelectronic and excitonic properties in a series of linear acenes (naphthalene up to heptacene) are investigated using range-separated methods within time-dependent density functional theory (TDDFT). In these rather simple systems, it is well-known that TDDFT methods using conventional hybrid functionals surprisingly fail in describing the low-lying La and Lb valence states, resulting in large, growing errors for the La state and an incorrect energetic ordering as a function of molecular size. In this work, we demonstrate that the range-separated formalism largely eliminates both of these errors and also provides a consistent description of excitonic properties in these systems. We further demonstrate that re-optimizing the percentage of Hartree-Fock exchange in conventional hybrids to match wavefunction-based benchmark calculations still yields serious errors, and a full 100% Hartree-Fock range separation is essential for simultaneously describing both of the La and Lb transitions. Based on an analysis of electron-hole transition density matrices, we finally show that conventional hybrid functionals overdelocalize excitons and underestimate quasiparticle energy gaps in the acene systems. The results of our present study emphasize the importance of both a range-separated and asymptotically-correct contribution of exchange in TDDFT for investigating optoelectronic and excitonic properties, even for these simple valence excitations.Comment: Accepted by the Journal of Chemical Theory and Computatio

A quantum-chemical study of the binding ability of βXaaHisGlyHis towards copper(II) ion

The present study analyzed binding of Cu2+ to tetrapeptides in water solution at several levels of theoretical approximation. The methods used to study the energetic and structural properties of the complexes in question include semiempirical hamiltonians, density functional theory as well as ab initio approaches including electron correlation effects. In order to shed light on the character of interactions between Cu2+ and peptides, which are expected to be mainly electrostatic in nature, decomposition of interaction energy into physically meaningful components was applied

Open Babel: An open chemical toolbox

Background: A frequent problem in computational modeling is the interconversion of chemical structures between different formats. While standard interchange formats exist (for example, Chemical Markup Language) and de facto standards have arisen (for example, SMILES format), the need to interconvert formats is a continuing problem due to the multitude of different application areas for chemistry data, differences in the data stored by different formats (0D versus 3D, for example), and competition between software along with a lack of vendorneutral formats. Results: We discuss, for the first time, Open Babel, an open-source chemical toolbox that speaks the many languages of chemical data. Open Babel version 2.3 interconverts over 110 formats. The need to represent such a wide variety of chemical and molecular data requires a library that implements a wide range of cheminformatics algorithms, from partial charge assignment and aromaticity detection, to bond order perception and canonicalization. We detail the implementation of Open Babel, describe key advances in the 2.3 release, and outline a variety of uses both in terms of software products and scientific research, including applications far beyond simple format interconversion. Conclusions: Open Babel presents a solution to the proliferation of multiple chemical file formats. In addition, it provides a variety of useful utilities from conformer searching and 2D depiction, to filtering, batch conversion, and substructure and similarity searching. For developers, it can be used as a programming library to handle chemical data in areas such as organic chemistry, drug design, materials science, and computational chemistry. It is freely available under an open-source license fro

Nature of the bonding in metal-silane σ-complexes

The nature of metal silane σ-bond interaction has been investigated in several key systems by a range of experimental and computational techniques. The structure of [Cp′Mn(CO)2(η2-HSiHPh2)] 1 has been determined by single crystal neutron diffraction, and the geometry at the Si atom is shown to approximate a trigonal bipyramid; salient bond distances and angles are Mn−H(1) 1.575(14), Si−H(1) 1.806(14), Si−H(2) 1.501(13) Å, and H(1)−Si−H(2) 148.5(8)°. This complex is similar to [Cp′Mn(CO)2(η2-HSiFPh2)] 2, whose structure and bonding characteristics have recently been determined by charge density studies based on high-resolution X-ray and neutron diffraction data. The geometry at the Si atom in these σ-bond complexes is compared with that in other systems containing hypercoordinate silicon. The Mn−H distances for 1 and 2 in solution have been estimated using NMR T1 relaxation measurements, giving a value of 1.56(3) Å in each case, in excellent agreement with the distances deduced from neutron diffraction. Density functional theory calculations have been employed to explore the bonding in the Mn−H−Si unit in 1 and 2 and in the related system [Cp′Mn(CO)2(η2-HSiCl3)] 3. These studies support the idea that the oxidative addition of a silane ligand to a transition metal center may be described as an asymmetric process in which the Mn−H bond is formed at an early stage, while both the establishment of the Mn−Si bond and also the activation of the η2-coordinated Si−H moiety are controlled by the extent of Mn → σ*(X−Si−H) back-donation, which increases with increasing electron-withdrawing character of the X substituent trans to the metal-coordinated Si−H bond. This delocalized molecular orbital (MO) approach is complemented and supported by combined experimental and theoretical charge density studies: the source function S(r,Ω), which provides a measure of the relative importance of each atom’s contribution to the density at a specific reference point r, clearly shows that all three atoms of the Mn(η2-SiH) moiety contribute to a very similar extent to the density at the Mn−Si bond critical point, in pleasing agreement with the MO model. Hence, we advance a consistent and unifying concept which accounts for the degree of Si−H activation in these silane σ-bond complexes