A review on point mutations via proton transfer in DNA base pairs in the absence and presence of electric fields.

This comprehensive review focuses on spontaneous mutations that may occur during DNA replication, the fundamental process responsible for transferring genetic information. In 1963, Löwdin postulated that these mutations are primarily a result of proton transfer reactions within the hydrogen-bonded DNA base pairs. The single and double proton transfer reactions within the base pairs in DNA result in zwitterions and rare tautomers, respectively.

Average Electron Density: A Quantitative Tool for Evaluating Non-Classical Bioisosteres of Amides.

Bioisosterism is strategically used in drug design to enhance the pharmacokinetic and pharmacodynamic properties of therapeutic molecules. The average electron density (AED) tool has been used in several studies to quantify similarities among nonclassical bioisosteres of carboxylic acid. In this study, the AED tool is used to quantify the similarities among nonclassical bioisosteres of an amide group.

Quantum and Classical Evaluations of Carboxylic Acid Bioisosteres: From Capped Moieties to a Drug Molecule.

Using the Quantum Theory of Atoms in Molecules, the average electron density (AED) tool was developed and employed to quantitatively evaluate the similarities between bioisosteric moieties in drug design. Bioisosteric replacements are valuable in drug molecules to fine-tune their pharmacokinetic and pharmacodynamic properties while maintaining their biological activity. This study was performed on non-classical bioisosteres of carboxylic acid.

Research performance of the GCC countries: A comparative analysis of quantity and quality.

Given the increased focus on scientific research in the Gulf Cooperation Council (GCC) countries, it is important to have a thorough bibliometric study about their research productivity and its progress over a long period of time. Using the world's largest bibliometric database (Scival/Scopus), we analyzed the research output of the GCC countries, from 1996 to 2020, in various disciplines. We considered raw metrics of quantity (number of articles) and quality (citations, citations/article, and Field-Weighted Citation Impact -FWCI), and then normalized them to population size, Gross Domestic Product (GDP), Gross Expenditure on Research and Development (GERD), and number of researchers.

Diastereoselective Additions of Allylmagnesium Reagents to α-Substituted Ketones When Stereochemical Models Cannot Be Used.

The stereoselectivities of reactions of allylmagnesium reagents with chiral ketones cannot be easily explained by stereochemical models. Competition experiments indicate that the complexation step is not reversible, so nucleophiles cannot access the widest range of possible encounter complexes and therefore cannot be analyzed easily using available models. Nevertheless, additions of allylmagnesium reagents to a ketone can still be stereoselective provided that the carbonyl group adopts a conformation that leads to one face being completely blocked from the approach of the allylmagnesium reagent.

The influence of external electric fields on proton transfer tautomerism in the guanine-cytosine base pair.

The Watson-Crick base pair proton transfer tautomers would be widely considered as a source of spontaneous mutations in DNA replication if not for their short lifetimes and thermodynamic instability. This work investigates the effects external electric fields have on the stability of the guanine-cytosine proton transfer tautomers within a realistic strand of aqueous DNA using a combination of ensemble-based classical molecular dynamics (MD) coupled to quantum mechanics/molecular mechanics (QM/MM). Performing an ensemble of calculations accounts for the stochastic aspects of the simulations while allowing for easier identification of systematic errors.

Atomic and molecular properties of nonclassical bioisosteric replacements of the carboxylic acid group.

Drug design is fraught with challenges as small differences in the structure of a drug molecule can significantly affect its biological activity. Bioisosteres are interchangeably used to adjust pharmacokinetic and pharmacodynamic properties without affecting the biological activity of the drug. While electrostatic potential maps (EPMs) are typically used to show the similarity in the 'key and lock' interactions between a drug and its receptor, they are limited to qualitative comparisons.

Effects of Intense Electric Fields on the Double Proton Transfer in the Watson-Crick Guanine-Cytosine Base Pair.

The double proton transfer reaction in the guanine-cytosine (GC) base pair is studied, using density functional theory, to understand the chances of mutations under the effect of uniform electric fields in the order of 10 to 10 V m. On the basis of potential energy surfaces, reaction Gibbs energies, equilibrium constants, imaginary frequencies, forward and reverse barrier heights, tunneling-corrected rate constants, half-lives of the forward and reverse reactions, percent tautomerization, and Boltzmann distributions, it was found that fields ≥+3.60 × 10 V m facilitate the mutation in the GC base pair and reduce the rectification of point mutations.

Adenine-thymine tautomerization under the influence of strong homogeneous electric fields.

The effect of strong electric fields on the tautomerization of the adenine-thymine (AT) base pair in DNA is explored using density functional theory. It was found that the AT base pair is not likely to undergo a double proton transfer reaction even in the presence of electric fields ranging from 5.14 × 108 to 5.

Routes to drug design via bioisosterism of carboxyl and sulfonamide groups.

Aim: The similarity in the biological function of the bioisosteric pair, carboxyl and sulfonamide functional groups, is studied using the quantitative tool, average electron density of the bioisosteric moiety in drug molecules and the qualitative tool, electrostatic potential. Results/methodology: Five different capping groups (methyl, phenyl, chlorine, hydrogen and amine) were considered to investigate the effect of the environment on the properties of the bioisosteres. The molecules were considered in their neutral and anionic forms to account for the change in pH depending on the medium of the drug-receptor interactions.

Distribution of heavy metals around the Barakah nuclear power plant in the United Arab Emirates.

Inductively coupled plasma emission spectroscopy was used to measure the concentrations of heavy metals in 58 samples collected from the Barakah nuclear power plant (BNPP) area, UAE. The grain size distribution was symmetric, but the samples ranged from fine to coarse sand. The inverse relationship between grain size and heavy metal contaminations was validated.

Evaluating dispersion forces for optimization of van der Waals complexes using a non-empirical functional.

Modelling dispersion interactions with traditional density functional theory (DFT) is a challenge that has been extensively addressed in the past decade. The exchange-dipole moment (XDM), among others, is a non-empirical add-on dispersion correction model in DFT. The functional PW86+PBE+XDM for exchange, correlation and dispersion, respectively, compromises an accurate functional for thermochemistry and for van der Waals (vdW) complexes at equilibrium and non-equilibrium geometries.

Electrostatic potentials and average electron densities of bioisosteres in methylsquarate and acetic acid.

Background: The bioisosterism in -CO2H and -C4HO3 is exploited using the quantum theory of atoms in molecules and molecular electrostatic potentials (ESP).

Results & Discussion: Bioisosteres in methylsquarate and acetic acid, in the neutral/anionic forms, have average electron densities that differ by less than 2% (i.e.

Distribution of heavy metals in the coastal area of Abu Dhabi in the United Arab Emirates.

Fifty-seven sediment samples were collected from Abu Dhabi coastal area, United Arab Emirates (UAE). The concentrations of heavy metals including antimony, arsenic, barium, cadmium, cobalt, copper, mercury, lead, molybdenum, nickel and zinc were obtained using Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS) and X-ray fluorescence. Heavy metal contaminations in Abu Dhabi had increased since 2004.

Assessment of the PW86+PBE+XDM density functional on van der Waals complexes at non-equilibrium geometries.

The deficiency of conventional density-functional theory (DFT) in properly describing van der Waals (vdW) (especially dispersion-bound) complexes has been extensively addressed in the past decade. There are now several new methods published in the literature that are capable of accurately capturing weak dispersion interactions in complexes at equilibrium geometries. However, the performance of these new methods at non-equilibrium geometries remains to be assessed.

Effects of external electric fields on double proton transfer kinetics in the formic acid dimer.

Molecules can be exposed to strong local electric fields of the order of 10(8)-10(10) V m(-1) in the biological milieu. The effects of such fields on the rate constant (k) of a model reaction, the double-proton transfer reaction in the formic acid dimer (FAD), are investigated. The barrier heights and shapes are calculated in the absence and presence of several static homogenous external fields ranging from 5.

Electron-density descriptors as predictors in quantitative structure--activity/property relationships and drug design.

The use of electron density-based molecular descriptors in drug research, particularly in quantitative structure--activity relationships/quantitative structure--property relationships studies, is reviewed. The exposition starts by a discussion of molecular similarity and transferability in terms of the underlying electron density, which leads to a qualitative introduction to the quantum theory of atoms in molecules (QTAIM). The starting point of QTAIM is the topological analysis of the molecular electron-density distributions to extract atomic and bond properties that characterize every atom and bond in the molecule.

The bioisosteric similarity of the tetrazole and carboxylate anions: clues from the topologies of the electrostatic potential and of the electron density.

There is a need for an a priori method with which to demonstrate the physical similarities between non-classical bioisosteres. In this study we explore the utility of the electron density and the electrostatic potential as the basis for a systematic investigation of the physical and chemical similarities between bioisosteres. The tetrazole and carboxylate bioisosteric pair is used as an illustrative example.

Where is electronic energy stored in adenosine triphosphate?

The gas-phase electronic energy of the hydrolysis of methyl triphosphate, a model of adenosine 5'-triphosphate (ATP), is partitioned into local (atomic and group) contributions. A modified definition of Lipmann's "group transfer potential" is proposed on the basis of the partitioning of the total electronic energy into atomic contributions within the framework of the quantum theory of atoms in molecules (QTAIM). The group transfer potential is defined here as the sum of the atomic energies forming the group in ATP minus the sum of the energies of the same atoms in inorganic phosphate.

Atomic partitioning of the dissociation energy of the P-O(H) bond in hydrogen phosphate anion (HPO4(2-)): disentangling the effect of Mg2+.

This paper has three goals: (1) to provide a first step in understanding the atomic basis of the role of magnesium in facilitating the dissociation of the P-O bond in phosphorylated biochemical fuel molecules (such as ATP or GTP), (2) to compare second-order Møller-Plesset perturbation theory (MP2) results with those obtained at the more economical density functional theory (DFT) level for a future study of larger more realistic models of ATP/GTP, and (3) to examine the calculation of atomic total energies from atomic kinetic energies within a Kohn-Sham implemention of DFT, as compared to ab initio methods. A newly described method based on the quantum theory of atoms in molecules (QTAIM), which is termed the "atomic partitioning of the bond dissociation energy" (APBDE), is applied to a simple model of phosphorylated biological molecules (HPO42-). The APBDE approach is applied in the presence and in the absence of magnesium.