This article reviews efforts in accurate experimental charge-density studies with relevance to medicinal chemistry. Initially, classical charge-density studies that measure electron density ...distribution via least-squares refinement of aspherical-atom population parameters are summarized. Next, interaction density is discussed as an idealized situation resembling drug-receptor interactions. Scattering-factor databases play an increasing role in charge-density research, and they can be applied both to small-molecule and macromolecular structures in refinement and analysis; software development facilitates their use. Therefore combining both of these complementary branches of X-ray crystallography is recommended, and examples are given where such a combination already proved useful. On the side of the experiment, new pixel detectors are allowing rapid measurements, thereby enabling both high-throughput small-molecule studies and macromolecular structure determination to higher resolutions. Currently, the most ambitious studies compute intermolecular interaction energies of drug-receptor complexes, and it is recommended that future studies benefit from recent method developments. Selected new developments in theoretical charge-density studies are discussed with emphasis on its symbiotic relation to crystallography.
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•The accuracy of the “kernel energy method” is due to an atom-level error cancellation.•The energies of the kernels can be an order of magnitude more accurate than those of the ...composing atoms.•IQA provides an insightful decomposition of the errors of the KEM approximation.
The Kernel Energy Method (KEM) has been widely applied to predict the properties of large molecules from kernels fragments in a fast and reliable manner. Kernels are typically made of many atoms raising the question: Is the accuracy of KEM traceable to the atomic level? An exact atomic decomposition of the molecular energy within the Quantum Theory of Atoms in Molecules (QTAIM), termed “Interacting Quantum Atoms (IQA)”, performed on a triglycyl model demonstrates that this is not the case. The kernel energies are found to be up to an order of magnitude more accurate than the underlying IQA atomic energies. The accuracy of KEM energies is, thus, the result of a subtle cancellation of errors among the different atoms composing the kernels.
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•NEMD simulations examined ion separation in porous borophene via electric fields.•Research targets applying computational desalination findings to seawater treatment.•Enhanced ion ...separation efficiency was linked to electric field strength and pore size.•Separation efficiency rose until hitting a plateau at a critical pore size.
Utilizing non-equilibrium molecular dynamics simulations, we examined the ion separation facilitated by an electric field through a borophene sheet with pores. This research was inspired by the potential use of such a system in membrane-driven desalination of sea and ocean waters. Our findings indicate a marked improvement in separating both negative and positive ions from water, contingent upon electric field strength and the radius of the membrane pore. Notably, beyond a specific pore radius, this enhancement reaches a saturation point. The results highlight the potential of a high-efficiency system for producing fresh water from saline sources, emphasizing the synergistic effect of membrane porosity and the strength of the applied electric field.
Professor Lou Massa’s contributions since the late 1960s to the founding of the field now known as “
Quantum Crystallography
” (QCr) are briefly described. The term itself has been coined in 1995 by ...L. Huang,
L. Massa
, and J. Karle (1985 Nobel Laureate in Chemistry). Originally, QCr referred to the Clinton-Massa’s iterative approach that, for the first time, delivered
N
-representable electron densities that are consistent with the observed structure factors
.
These densities satisfy, at once, experimental observation and the necessarily underlying quantum mechanical requirement of being derived from an antisymmetric wavefunction. The single-determinantal quantum mechanical structure Huang, Massa, and Karle (HMK) imposed in their original work can be extended to any method that uses MOs including CI or DFT, as they demonstrate in their papers. HMK use the Clinton-Massa method to reconstruct approximations to the first order reduced density matrix of large molecules in a piecemeal manner from computationally-tractable fragments. The idea was also adapted by J. Hernández Trujillo and R. F. W. Bader in the context of the Quantum Theory of Atoms in Molecules (QTAIM). Massa et al. simplified and generalized this fragmentation method into what came to be known as the “
Kernel Energy Method
” (KEM) which delivers the properties of large molecules accurately, at a fraction of the computational time, and within any model chemistry as applications to DNA, tRNA, the proto-ribosome, insulin, and graphene, amply demonstrate. Lou Massa has also pushed the envelope in other directions as well. In 1992, he and W. Lipscomb (1976 Nobel Laureate in Chemistry) published several papers predicting the structure and stability of Boron nanotubes and boron fullurene 12 years before they were eventually synthesized in laboratories at Yale and at Brookhaven. More recently, in 2006 L. Massa, J. Karle, and A. Yonath (2009 Nobel Laureate in Chemistry) (MKY) proposed a startling alternative to the then widely-accepted mechanism of the peptide bond formation in the active site of the ribosome. In sharp contrast with the accepted “
shuttle mechanism
”, MKY’s “
direct
” mechanism is simpler and, importantly, reproduces the measured thermodynamic and kinetic parameters. Massa has also contributed to other domains, for example interstellar chemistry, and to the policy, history, and philosophy of science. His TV program and Oxford University Press book (both titled “
Science and the Written Word
”) represent an invaluable and candid documentation of some of the key discoveries in the words of a dozen Nobel Laureates and a constellation of scholars representing the Who’s Who of current science. It is with both admiration and affection that this paper (and this issue) is dedicated to Lou Massa, the person and the scientist.
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•New magnetic semiconductors RbLnSe2 (Ln = Ce, Pr, Nd, Gd) are proposed on the basis of DFT calculations.•Spin-polarized calculations predict a higher stability for the ferromagnetic ...configuration.•The splitting of 4f-Ln states drives the ferromagnetic character and magnetic moments increase with the band gap.•RbLnSe2 compounds are semiconductors with two spin band gap channels in both spin directions.•Physical properties of RbNdSe2 and RbGdSe2 suggest their use in photoresponse applications.
The structural, magnetic, electronic, and elastic properties of magnetic semiconductors RbLnSe2 (Ln = Ce, Pr, Nd and Gd) are elucidated using density functional theory (DFT) using both large and small core pseudopotentials for the lanthanide atoms. Magnetic ordering is investigated using spin-polarized calculations, and the higher stability of ferromagnetic configuration is predicted. It is found that the splitting of 4f-Ln states drives the ferromagnetic character of these materials and that the total and partial magnetic moments increase with the energy band gap. The RbLnSe2 compounds are found to be semiconductors with two spin band gap channels (Eg1 and Eg2) in both spin directions. The band gaps of RbNdSe2 and RbGdSe2 suggest their possible usefulness in photoresponse applications. The mechanical stabilities and elastic properties of RbLnSe2 were calculated for the single and poly-crystals and reinforce the suggestion of their potential photoresponse and spintronic technological applications.
Present-day known predominance of the β- over the α-anomers in nucleosides and nucleotides emerges from a thermodynamic analysis of their assembly from their components, i.e. bases, sugars, and a ...phosphate group. Furthermore, the incorporation of uracil into RNA and thymine into DNA rather than the other way around is also predicted from the calculations. An interplay of kinetics and thermodynamics must have driven evolutionary selection of life's building blocks. In this work, based on quantum chemical calculations, we focus on the latter control as a tool for “natural selection”.
Prebiotic chemistry; Nucleosides; Nucleotides; Uracil and thymine; Anomers of nucleosides and nucleotides; Density functional theory (DFT) calculations
The fate of dimensions of dimensioned quantities that are inserted into the argument of transcendental functions such as logarithms, exponentiation, trigonometric, and hyperbolic functions is ...discussed. Emphasis is placed on common misconceptions that are not often systematically examined in undergraduate courses of physical sciences. The argument of dimensional inhomogeneity of the terms of a Taylor expansion of a transcendental function presented in some nonpeer-reviewed popular Internet sites is shown to be false.
The electron density and the electron localization‐delocalization matrices (LDMs) are used to revisit the cyclooctetraene (COT) dimerization mechanism. The global minimum of a COT monomer (the tub ...geometry) exhibits a rare topological feature, giving rise, not to one, but to two ring critical points and a cage critical point necessary to satisfy the Poincaré‐Hopf relation. The energy profiles were used to identify the rate‐limiting step of the reaction: the penultimate transition state of a series of five transition states in total. While the monomers themselves have zero dipolar polarization, the dimer has a nonnegligible total dipole moment reaching almost 1 debye with fluctuations in strength and orientation along the reaction path. The reaction can hence, possibly, be manipulated with intense laser fields. This classic reaction has been used to elucidate whether the electron LDMs reflect structural or energetic similarity. It is found that LDMs are excellent monitors of structural/electronic similarity between different species on the reaction coordinate. A reaction can be characterized by a three‐dimensional hypermatrix whereby the matrix elements change as a function of the reaction coordinate, which can be represented as a parallelepiped of matrix elements. A study of the electron density of the system as the reaction progresses identifies and characterizes the bond paths that drive the reaction. It is hoped that this dynamic picture of the evolution of the electron density complements the usual arrow pushing reaction mechanisms used by organic chemists.
A representation of the evolution of the electron localization‐delocalization matrix (LDM) of the system (dimerization of cyclooctatetraene) as a function of the reaction coordinate.
A new and powerful molecular descriptor termed the LDM (localization-delocalization matrix) has recently been proposed as a molecular fingerprinting tool and has been shown to yield robust ...quantitative-structure-to-activity/property-relationships (QSAR/QSPR). An LDM lists the average number of electrons localized within an atom in a molecule along its diagonal while the off-diagonal elements are the pair-wise average number of electrons shared between every pair of atoms in the molecule, bonded or not. Hence, the LDM is a representation of a fuzzy molecular graph that accounts for the whereabouts of all electron(s) in the molecule and can be expected to encode for several facets of its chemistry at once. We show that the LDM captures the aromatic character of a ring-in-a-molecule by comparing the aromaticity ranking based on the LDMs and their eigenvalues of 6-membered carbon rings within (polycyclic) benzenoid hydrocarbons with the ranking based on four well-established local aromaticity measures (harmonic oscillator model of aromaticity, acromatic fluctuation index, para delocalization index, and nucleus independent chemical shift(0)).
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