Dan Thomas Major

Bar Ilan University | BIU · Department of Chemistry

TiO2 material has gained significant attention for large‐scale energy storage due to its abundant, low‐cost, and environmentally friendly properties, as well as the availability of various nanostructures. Phosphorus doping has been established as an effective technique for improving electronic conductivity and managing the slow ionic diffusion kine...

Ni-rich, Co-free layered oxide cathode materials are promising candidates for next-generation Li-ion batteries due to their high energy density. However, these cathode materials suffer from rapid capacity fading during electrochemical cycling. To overcome this shortcoming, so-called high-entropy (HE) materials, which are obtained by incorporating m...

The introduction of the water‐in‐salt (WIS) concept, using highly concentrated electrolyte solutions to prevent water splitting and widen the electrochemical stability window, has greatly influenced modern aqueous batteries. The successful implementation of these electrolyte solutions in many electrochemical systems shifts the focus from diluted to...

The introduction of the water‐in‐salt (WIS) concept, using highly concentrated electrolyte solutions to prevent water splitting and widen the electrochemical stability window, has greatly influenced modern aqueous batteries. The successful implementation of these electrolyte solutions in many electrochemical systems shifts the focus from diluted to...

The G- and V-type nerve agents are among the most toxic compounds known, where inhalation of a few mg could cause potential death. Over the years, wild-type phosphotriesterase (PTE) has gained much attention due to its capability of detoxifying these deadly compounds. The underlying mechanism proceeds via a hydroxyl attack on the P or C centers of...

Spin–orbit coupling (SOC) combined with broken inversion symmetry plays a key role in inducing Rashba effect. The combined spontaneous polarization and Rashba effect enables controlling a material's spin degrees of freedom electrically. In this work, we investigated an electronic band structure for several combinations of TiX2 monolayers (X = Te, S...

Lithiated oxides like Li[NixCoyMnz]O2 (x+y+z=1) with high nickel content (x≥0.8) can possess high specific capacity ≥ 200 mAhg-1 and have attracted extensive attention as perspective cathode materials for advanced lithium-ion batteries. In this work, we synthesized LiNi0.9Co0.1O2 (NC90) materials and studied their structural characteristics, electr...

The rate of proton abstraction of the carbon acid nitroethane by Asp402 is accelerated by a factor of 108 in the enzyme nitroalkane oxidase (NAO) relative to that by the organic base acetate ion in water. The Cα proton of nitroalkanes is known to exhibit an abnormal correlation between its acidity strength and the rate of deprotonation, with an unu...

Spin-orbit coupling (SOC) combined with broken inversion symmetry play key roles in inducing Rashba effect. The combined spontaneous polarization and Rashba effect enable controlling a material's spin degrees of freedom electrically. In this work we investigated the electronic band structure for several combinations of TiX2 monolayers (X= Te, S and...

It has been recently shown that SmI2 is more azaphilic than oxophilic. Density functional theory calculations reveal that coordination of 1-3 molecules of ethylenediamine is more exothermic by up to 10 kcal/mol than coordination of the corresponding number of ethylene glycol molecules. Taking into account also hydrogen bonds between ligands and tet...

Copper is an essential element in nature but in excess it is toxic to the living cell. The human metallochaperone Atox1 participates in copper homeostasis and is responsible for copper transmission. In a previous multiscale simulation study, we noticed a change in the coordination state of the Cu(I) ion, from 4 bound cysteine residues to 3, in agre...

Quantum tunneling (QT) is not an effect often considered in chemistry, and rightfully so. However, in many cases it is significant, and in some cases it is even considerable. In this chapter we will describe the basic tenets of QT with a focus on catalysis, followed by some of the most important tools to study and compute them. The chapter goes on...

Ni-rich LiNi1–x–yCoxMnyO2 (1 – x – y > 0.5) (NCMs) cathode materials have shown great promise in energy-intensive applications, such as electric vehicles. However, as many layered cathodes do, they suffer from structural and electrochemical degradation during cycling. In this study, we show that Nd- and Y-doped materials, Li(Ni0.85Co0.1Mn0.05)0.995...

Terpene synthases are responsible for the biosynthesis of terpenes, the largest family of natural products. Hydropyrene synthase generates hydropyrene and hydropyrenol as its main products along with two byproducts, isoelisabethatrienes A and B. Fascinatingly, a single active site mutation (M75L) diverts the product distribution towards isoelisabet...

Terpene synthases are responsible for the biosynthesis of terpenes, the largest family of natural products. Hydropyrene synthase generates hydropyrene and hydropyrenol as its main products along with two byproducts, isoelisabethatriene A and B. Fascinatingly, a single active site mutation (M75L) diverts the product distribution towards isoelisabeth...

Extensive efforts are currently underway to develop safe and cost-effective electrolytes for large-scale energy storage. In this regard, water-based electrolytes may be an attractive option, but their narrow electrochemical stability window hinders their realization. Although highly concentrated fluorinated electrolytes have been shown to be highly...

This work is part of ongoing and systematic investigations by our groups on the synthesis, electrochemical behavior, structural investigations, and computational modeling of the Ni-rich materials Li[NixCoyMnz]O2 (x+y+z=1; x≥0.8) for advanced lithium-ion batteries. This study focuses on the LiNi0.85Co0.10Mn0.05O2 (NCM85) material and its improvement...

The specific capacity of Ni rich LiNixCoyMnzO2x>0.5 ) cathodes is higher as their Ni content is higher and can reach values up to 240 mAh g⁻¹ (x →1) while being charged below 4.3 V vs Li. This property is very important since charging Li-ion batteries below this potential is not detrimental to anodic stability of the electrolyte solution. However,...

The coronavirus SARS-CoV-2 main protease, Mpro, is conserved among coronaviruses with no human homolog and has therefore attracted significant attention as an enzyme drug target for COVID-19. The number of studies targeting Mpro for in silico screening has grown rapidly, and it would be of great interest to know in advance how well docking methods...

Calculation of temperature-dependent kinetic isotope effects (KIE) in enzymes presents a significant theoretical challenge. Additionally, it is not trivial to identify enzymes with available experimental accurate intrinsic KIEs in a range of temperatures. In the current work, we present a theoretical study of KIEs in the primitive R67 dihydrofolate...

The sizes of available self‐assembled hydrogen bond based supramolecular capsules and cages are rather limited. The largest systems feature volumes of approx. 1400 − 2300 Å3. Here, we report a large, hexameric cage based on intermolecular amide−amide dimerization. The unusual structure with openings, reminiscent of covalently linked cages, is held...

Terpene synthases generate terpenes employing diversified carbocation chemistry, including highly specific ring formations, proton and hydride transfers, and methyl as well as methylene migrations, followed by reaction quenching. In this enzyme family, the main catalytic challenge is not rate enhancement, but rather structural and reactive control...

In this opinion, we review some recent work on terpene biosynthesis using multiscale simulation approaches, with special focus on contributions from our group. Terpene synthases generate terpenes employing rich carbocation chemistry, including highly specific ring formations, proton, hydride, methyl, and methylene migrations, followed by reaction q...

Aqueous sodium‐ion batteries are expected to be low‐cost, safe, and environmentally friendly systems for large scale energy storage due to the abundance and low cost of sodium. However, only a few candidates have been reported for cathodes and there is a need to develop new practical host materials with improved electrochemical performance. Here, t...

Lithium transition metal olivine phosphates are well known Li-ion battery cathode materials, but these materials can also be used as electrocatalyst. Recent experimental studies showed that olivine phosphates with mixed alkali metals (Li and Na) and mixed transition metals (Ni and Fe) provide better electrocatalytic activity compared to single alka...

Terpene and terpenoid synthesis are challenging tasks because of the required multiple synthetic steps, exact functionalization, and difficult purification that reduce the yields. One of the propitious methods to tackle this problem is synthesis of terpenes inside nano capsules. Nano capsules based on resorcinarene moieties have recently been emplo...

Atox1 is a human copper metallochaperone that is responsible for transferring copper ions from the main human copper transporter, hCtr1, to ATP7A/B in the Golgi apparatus. Atox1 interacts with the Ctr1 C-terminal domain as a dimer, although it transfers the copper ions to ATP7A/B in a monomeric form. The copper binding site in the Atox1 dimer invol...

Terpenes constitute one of the most structurally varied classes of natural products. A wide range of these structures are produced in nature by type I terpene cyclase enzymes from one single substrate. However, such reactivity has prov-en difficult to reproduce in solution with man-made systems. Herein we report the shortest synthesis of the tricyc...

Terpene cyclases are responsible for the initial cyclization cascade in the multistep synthesis of a large number of terpenes. CotB2 is a diterpene cyclase from Streptomyces melanosporofaciens, which catalyzes the formation of cycloocta-9-en-7-ol, a precursor to the next-generation anti-inflammatory drug cyclooctatin. In this work, we present evide...

Lithium‐ion based rechargeable batteries are considered among the most promising battery technologies because of the high energy‐ and power‐densities of these electrochemical devices. Computational studies on lithium ion batteries (LIBs) facilitate rationalization and prediction of many important experimentally observed properties, including atomic...

At present the most successful rechargeable battery is the Li-ion battery, due to the small size, high energy density and low reduction potential of Li. Computational materials science has become an increasingly important tool to study these batteries, and in particular cathode properties. In silico studies of cathode materials have proven to be a...

ion from ethanol by atomic hydrogen in aqueous solution is studied using two theoretical approaches; multi-path variational transition state theory (MP-VTST) and a path integral formalism in combination with free-energy perturbation and umbrella sampling (PI-FEP/UM). The performance of the models is compared to experimental values of H kinetic isot...

Bio-inspired transition metal complexes may serve as efficient and low-cost potential catalysts for oxygen reduction reaction (ORR) in fuel cells, instead of precious group metal-free (PGM-free) materials. Herein, we present the study of ORR electrocatalytic activity of different meso-substituted Co-corroles with varying electronegativity using bot...

Thermal motions of enzymes have been invoked to explain the temperature dependence of kinetic isotope effects (KIE) in enzyme-catalyzed hydride transfers. Formate dehydrogenase (FDH) from Candida boidinii exhibits a temperature independent KIE that becomes temperature dependent upon mutation of hydrophobic residues in the active site. Ternary compl...

CotB2 catalyzes the first committed step in cyclooctatin biosynthesis of the soil bacterium Streptomyces melanosporofaciens. To date, CotB2 represents the best studied bacterial diterpene synthase. Its reaction mechanism has been addressed by isoptope labeling, targeted mutagenesis and theoretical computations in the gas phase, as well as full enzy...

Effects of Cu-doping on the structural and magnetic properties of spin chain compound MnV2O6 have been investigated through experimental and theoretical techniques. Significant change in magnetic properties with Cu-doping have been observed. Increasing defects and disorders with Cu-doping which often results in a breaking of infinite chains along b...

Terpene cyclases are responsible for the initial cyclization cascade in the multistep synthesis of a large number of terpenes. CotB2 is a diterpene cyclase from Streptomyces melanosporofaciens, which synthesizes the formation of cyclooctat-9-en-7-ol, a precursor to the next-generation anti-inflammatory drug, cyclooctatin. In this work, we present e...

Herein we report the shortest synthesis of the tricyclic sesquiterpene presilphiperfolan-1β-ol to date, utilizing the supramolecular resorcinarene capsule as catalyst for the key step. This synthetic approach also allows access to unnatural derivatives of the natural product, which would not be accessible through the biosynthetic machinery. Additio...

Enzymes play a pivotal role in all biological system. These biomachines are the most effective catalysts known, dramatically enhancing the rate of reactions by more than 10 orders of magnitude relative to the uncatalyzed reactions in solution. Predicting the correct, mechanis-tically appropriate binding modes for substrate, product, as well as all...

The work reported herein is an important continuation of our recent experimental and computational studies on Li[NixCoyMnz]O2 (x+y+z=1) cathode materials for Li ion batteries, containing minor amounts of multivalent cationic dopants like Al3+, Zr4+, W6+, Mo6+. Based on DFT calculations for LiNi0.8Co0.1Mn0.1O2, it was concluded that Mo6+ cations pre...

Large-scale production of natural products, such as terpenes, presents a significant scientific and technological challenge. One promising approach to tackle this problem is chemical synthesis inside nano-capsules, although enzyme-like control of such chemistry has not yet been achieved. In order to better understand the complex chemistry inside na...

LepI is a novel multifunctional enzyme that catalyzes stereoselective dehydration, Diels–Alder reaction, and retro-Claisen rearrangement. Here we report the crystal structure of LepI in complex with its co-factor S-adenosyl methionine (SAM). LepI forms a tetramer via the N-terminal helical domain and binds to a SAM molecule in the C-terminal cataly...

Finding renewable energy sources as alternatives to petroleum-based fuels is a current global challenge. One approach to address the energy shortage problem is through biofuels. A promising family of biofuels that has many of the needed fuel characteristics is terpenes. Herein we present a combined theoretical and statistical model for calculating...

Layered lithium intercalating transition metal oxides are promising cathode materials for Li-ion batteries. Here, we scrutinize the recently developed strongly constrained and appropriately normed (SCAN) density functional method to study structural, magnetic, and electrochemical properties of prototype cathode materials LiNiO2, LiCoO2, and LiMnO2...

In the present study, we address the effect of active site structure and dynamics of different dihydrofolate reductase (DHFR) isoforms on the pKa of the bound substrate 7,8-dihydrofolate, in an attempt to understand possible evolutionary trends. We apply a hybrid QM/MM free energy perturbation method to estimate the pKa of the N5 position of the bo...

Terpenes constitute the largest and structurally most diverse natural product family. Most terpenoids exhibit a stereochemically complex macrocyclic core, which is generated by C-C bond forming of aliphatic oligo-prenyl precursors. This reaction is catalysed by terpene synthases (TPSs), which are capable of chaperoning highly reactive carbocation i...

Extracellular nucleotides can regulate the production/drainage of the aqueous humor via activation of P2 receptors, thus affecting the intraocular pressure (IOP). We evaluated 5-OMe-UDP(α-B), 1A, a potent P2Y6-receptor agonist, for reducing IOP and treating glaucoma. Cell viability in the presence of 1A was measured using [3-(4, 5-dimethyl-thiazol-...

The chemical synthesis of natural products, such as sesquiterpenes, is a daunting task due to their complexity and precise functionalization, and multiple synthetic and purification steps that reduce overall yields are usually required. Now, a highly efficient alternative approach using supramolecular chemistry has been proposed by Tiefenbacher and...

Doping Ni-rich LiNi0.5Co0.2Mn0.3O2 (NCM523) cathode material by small amount of Mo6+ ions, around 1 mol.%, affects pronouncedly its structure, surface properties, electronic and electrochemical behavior. Cathodes comprising Mo6+ doped NCM523 exhibited in Li cells higher specific capacities, higher rate capabilities, lower capacity fading and lower...

Dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF) in the presence of NADPH. The key hydride transfer step in the reaction is facilitated by a combination of enzyme active site preorganization and correlated protein motions in the Michaelis-Menten (E:NADPH:DHF) complex. The present theoretical st...

Metallocorroles are transition metal complexes showing great promise as oxygen reduction reaction catalysts. The performance of metallocorrole catalysts is highly sensitive to the nature of the transition metal employed, although currently this dependence remains elusive. In the current work, we present a first principles density functional theory...

Layered lithium intercalating transition metal (TM) oxides are promising cathode materials for Li-ion batteries. Here we scrutinize the recently developed strongly constrained and appropriately normed (SCAN) density functional method to study structural, magnetic and electrochemical properties of prototype cathode materials LiNiO2, LiCoO2, and LiMn...

Development of advanced high energy density lithium ion batteries is important for promoting electromobility. Making electric vehicles attractive and competitive compared to conventional automobiles depends on the availability of reliable, safe, high power, and highly energetic batteries whose components are abundant and cost effective. Nickel rich...

Atomistic simulations have become one of the main approaches to study the chemistry and dynamics of biomolecular systems in solution. Chemical modelling is a powerful way to understand biochemistry, with a number of different programs available to perform specialized calculations. We present here Q6, a new version of the Q software package, which i...

Four β-pyrrole-substituted cobalt(III) corroles were studied as electrocatalysts for the oxygen reduction reaction. The results disclose high dependence of the corrole’s performance on its substituents, but once adsorbed on high...

Wang et al. recently reported an in silico study of the trichodiene synthase (TDS) conversion of farnesyl diphosphate (FPP) to trichodiene (TD) (Wang et al., ACS Catal. 2017, 7, 5841−5846). Although the methods and level of theory used in that work are nearly identical to our own recent work on this system (Dixit et al., ACS Catal. 2017, 7, 812-818...

Ni-rich lithiated layered oxides composed of Ni, Co and Mn (NCMs) have shown tremendous promise as cathode materials in lithium-ion batteries (LIB) for electro-mobility applications. The capacity of these materials increases with nickel content, but there is a concomitant decrease in stability and stable operating voltage during cycling. Hence, it...

One of the major hurdles of Ni-rich cathode materials Li1+x(NixCozMnz)wO2, y > 0.5 for lithium-ion batteries is their low cycling stability especially for compositions with Ni ≥ 60%, which suffer from severe capacity fading and impedance increase during cycling at elevated temperatures (e.g., 45 °C). Two promising surface and structural modificatio...

When a homogenous electric field is applied to polyynes (C10 and C20) perpendicular to their long axis, they bend to form an arch. The height of the arch is proportional to the intensity of the electric field. The direction of the bend and its magnitude depend on the electronic nature (donor/acceptor) of the substituents at the termini of the polyy...

Electrostatic interactions play a major role in stabilizing transition states in enzymes. A crucial question is how general this electrostatic stabilization principle is. To address this point, we study a key common C-C bond formation step in a family of enzymes that is responsible for the biosynthesis of 60% of all natural products. In these terpe...

A key question concerning the catalytic cycle of E. Coli Dihydrofolate Reductase (ecDHFR) is whether the M20 loop is dynamically coupled to the chemical step during catalysis. A more basic, yet unanswered question is whether the M20 loop adopts a closed conformation during the chemical hydride transfer step. To examine the most likely conformation...

Amongst a number of different cathode materials, the layered nickel-rich LiNiyCoxMn1−y−xO2and the integrated lithium-richxLi2MnO3·(1−x)Li[NiaCobMnc]O2(a+b+c= 1)have received considerable attention over the last decade due to their high capacities of ~195 and~250 mAh·g−1, respectively. Both materials are believed to play a vital role in the developm...