Accurate Potential Energy Surfaces Using Atom-Centered Potentials and Minimal High-Level Data.

We demonstrate that a Δ-density functional theory (Δ-DFT) approach based on atom-centered potentials (ACPs) represents a computationally inexpensive and accurate method for representing potential energy surfaces (PESs) for the HONO and HFCO molecules and vibrational frequencies derived therefrom. Using as few as 100 CCSD(T)-F12a reference energies, ACPs developed for use with B3LYP/def2-TZVPP are shown to produce PESs for HONO and HFCO with mean absolute errors of 27.7 and 5.8 cm-1, respectively. Application of the multiconfigurational time-dependent Hartree (MCTDH) method with ACP-corrected B3LYP/def2-TZVPP PESs produces vibrational frequencies for cis- and trans-HONO with mean absolute percent errors (MAPEs) of 0.8 and 1.1, compared to 0.8 obtained for the two isomers with CCSD(T)-F12a/cc-pVTZ-F12/MCTDH. For HFCO, the vibrational frequencies obtained using the present (Δ-DFT)/MCTDH approach give a MAPE of 0.1, which is the error obtained with CCSD(T)-F12a/cc-pVTZ-F12/MCTDH. The ACP approach is therefore successful in representing a PES calculated at a high level of theory (CCSD(T)-F12a) and a promising method for the development of a general protocol for the representation of accurate molecular PESs and the calculation of molecular properties from them.

Electrochemical PINOylation of Methylarenes: Improving the Scope and Utility of Benzylic Oxidation through Mediated Electrolysis.

A mediated electrosynthetic method has been developed for selective benzylic oxidation of methylarenes. Phthalimide-N-oxyl (PINO) radical generated by proton-coupled electrochemical oxidation of N-hydroxypthalimide serves as a hydrogen atom-transfer (HAT) mediator and as a radical trap for the benzylic radicals generated in situ. This mediated electrolysis method operates at much lower anode potentials relative to direct electrolysis methods for benzylic oxidation initiated by single-electron transfer (SET). A direct comparison of SET and mediated-HAT electrolysis methods with a common set of substrates shows that the HAT reaction exhibits a significantly improved substrate scope and functional group compatibility. The PINOylated products are readily converted into the corresponding benzylic alcohol or benzaldehyde derivative under photochemical conditions, and the synthetic utility of this method is highlighted by the late-stage functionalization of the non-steroidal anti-inflammatory drug celecoxib.

Are we failing female and racialized academics? A Canadian national survey examining the impacts of the COVID-19 pandemic on tenure and tenure-track faculty.

The novel coronavirus 2019 (COVID-19) pandemic caused the abrupt curtailment of on-campus research activities that amplified impacts experienced by female and racialized faculty. In this mixed-method study, we systematically and strategically unpack the impact of the shift of academic work environments to remote settings on tenured and tenure-track faculty in Canada. Our quantitative analysis demonstrated that female and racialized faculty experienced higher levels of stress, social isolation and lower well-being. Fewer women faculty felt support for health and wellness. Our qualitative data highlighted substantial gender inequities reported by female faculty such as increased caregiving burden that affected their research productivity. The most pronounced impacts were felt among pre-tenured female faculty. The present study urges university administration to take further action to support female and racialized faculty through substantial organizational change and reform. Given the disproportionate toll that female and racialized faculty experienced, we suggest a novel approach that include three dimensions of change: (1) establishing quantitative metrics to assess and evaluate pandemic-induced impact on research productivity, health and well-being, (2) coordinating collaborative responses with faculty unions across the nation to mitigate systemic inequities, and (3) strategically implementing a storytelling approach to amplify the experiences of marginalized populations such as women or racialized faculty and include those experiences as part of recommendations for change.

Small-Basis Set Density-Functional Theory Methods Corrected with Atom-Centered Potentials.

Density functional theory (DFT) is currently the most popular method for modeling noncovalent interactions and thermochemistry. The accurate calculation of noncovalent interaction energies, reaction energies, and barrier heights requires choosing an appropriate functional and, typically, a relatively large basis set. Deficiencies of the density-functional approximation and the use of a limited basis set are the leading sources of error in the calculation of noncovalent and thermochemical properties in molecular systems. In this article, we present three new DFT methods based on the BLYP, M06-2X, and CAM-B3LYP functionals in combination with the 6-31G* basis set and corrected with atom-centered potentials (ACPs). ACPs are one-electron potentials that have the same form as effective-core potentials, except they do not replace any electrons. The ACPs developed in this work are used to generate energy corrections to the underlying DFT/basis-set method such that the errors in predicted chemical properties are minimized while maintaining the low computational cost of the parent methods. ACPs were developed for the elements H, B, C, N, O, F, Si, P, S, and Cl. The ACP parameters were determined using an extensive training set of 118655 data points, mostly of complete basis set coupled-cluster level quality. The target molecular properties for the ACP-corrected methods include noncovalent interaction energies, molecular conformational energies, reaction energies, barrier heights, and bond separation energies. The ACPs were tested first on the training set and then on a validation set of 42567 additional data points. We show that the ACP-corrected methods can predict the target molecular properties with accuracy close to complete basis set wavefunction theory methods, but at a computational cost of double-ζ DFT methods. This makes the new BLYP/6-31G*-ACP, M06-2X/6-31G*-ACP, and CAM-B3LYP/6-31G*-ACP methods uniquely suited to the calculation of noncovalent, thermochemical, and kinetic properties in large molecular systems.

Fast and Accurate Quantum Mechanical Modeling of Large Molecular Systems Using Small Basis Set Hartree-Fock Methods Corrected with Atom-Centered Potentials.

There has been significant interest in developing fast and accurate quantum mechanical methods for modeling large molecular systems. In this work, by utilizing a machine learning regression technique, we have developed new low-cost quantum mechanical approaches to model large molecular systems. The developed approaches rely on using one-electron Gaussian-type functions called atom-centered potentials (ACPs) to correct for the basis set incompleteness and the lack of correlation effects in the underlying minimal or small basis set Hartree-Fock (HF) methods. In particular, ACPs are proposed for ten elements common in organic and bioorganic chemistry (H, B, C, N, O, F, Si, P, S, and Cl) and four different base methods: two minimal basis sets (MINIs and MINIX) plus a double-ζ basis set (6-31G*) in combination with dispersion-corrected HF (HF-D3/MINIs, HF-D3/MINIX, HF-D3/6-31G*) and the HF-3c method. The new ACPs are trained on a very large set (73 832 data points) of noncovalent properties (interaction and conformational energies) and validated additionally on a set of 32 048 data points. All reference data are of complete basis set coupled-cluster quality, mostly CCSD(T)/CBS. The proposed ACP-corrected methods are shown to give errors in the tenths of a kcal/mol range for noncovalent interaction energies and up to 2 kcal/mol for molecular conformational energies. More importantly, the average errors are similar in the training and validation sets, confirming the robustness and applicability of these methods outside the boundaries of the training set. In addition, the performance of the new ACP-corrected methods is similar to complete basis set density functional theory (DFT) but at a cost that is orders of magnitude lower, and the proposed ACPs can be used in any computational chemistry program that supports effective-core potentials without modification. It is also shown that ACPs improve the description of covalent and noncovalent bond geometries of the underlying methods and that the improvement brought about by the application of the ACPs is directly related to the number of atoms to which they are applied, allowing the treatment of systems containing some atoms for which ACPs are not available. Overall, the ACP-corrected methods proposed in this work constitute an alternative accurate, economical, and reliable quantum mechanical approach to describe the geometries, interaction energies, and conformational energies of systems with hundreds to thousands of atoms.

BH9, a New Comprehensive Benchmark Data Set for Barrier Heights and Reaction Energies: Assessment of Density Functional Approximations and Basis Set Incompleteness Potentials.

The calculation of accurate reaction energies and barrier heights is essential in computational studies of reaction mechanisms and thermochemistry. To assess methods regarding their ability to predict these two properties, high-quality benchmark sets are required that comprise a reasonably large and diverse set of organic reactions. Due to the time-consuming nature of both locating transition states and computing accurate reference energies for reactions involving large molecules, previous benchmark sets have been limited in scope, the number of reactions considered, and the size of the reactant and product molecules. Recent advances in coupled-cluster theory, in particular local correlation methods like DLPNO-CCSD(T), now allow the calculation of reaction energies and barrier heights for relatively large systems. In this work, we present a comprehensive and diverse benchmark set of barrier heights and reaction energies based on DLPNO-CCSD(T)/CBS called BH9. BH9 comprises 449 chemical reactions belonging to nine types common in organic chemistry and biochemistry. We examine the accuracy of DLPNO-CCSD(T) vis-a-vis canonical CCSD(T) for a subset of BH9 and conclude that, although there is a penalty in using the DLPNO approximation, the reference data are accurate enough to serve as a benchmark for density functional theory (DFT) methods. We then present two applications of the BH9 set. First, we examine the performance of several density functional approximations commonly used in thermochemical and mechanistic studies. Second, we assess our basis set incompleteness potentials regarding their ability to mitigate basis set incompleteness errors. The number of data points, the diversity of the reactions considered, and the relatively large size of the reactant molecules make BH9 the most comprehensive thermochemical benchmark set to date and a useful tool for the development and assessment of computational methods.

BSE49, a diverse, high-quality benchmark dataset of separation energies of chemical bonds.

We present an extensive and diverse dataset of bond separation energies associated with the homolytic cleavage of covalently bonded molecules (A-B) into their corresponding radical fragments (A. and B.). Our dataset contains two different classifications of model structures referred to as "Existing" (molecules with associated experimental data) and "Hypothetical" (molecules with no associated experimental data). In total, the dataset consists of 4502 datapoints (1969 datapoints from the Existing and 2533 datapoints from the Hypothetical classes). The dataset covers 49 unique X-Y type single bonds (except H-H, H-F, and H-Cl), where X and Y are H, B, C, N, O, F, Si, P, S, and Cl atoms. All the reference data was calculated at the (RO)CBS-QB3 level of theory. The reference bond separation energies are non-relativistic ground-state energy differences and contain no zero-point energy corrections. This new dataset of bond separation energies (BSE49) is presented as a high-quality reference dataset for assessing and developing computational chemistry methods.

Structure-function relationships in aryl diazirines reveal optimal design features to maximize C-H insertion.

Diazirine reagents allow for the ready generation of carbenes upon photochemical, thermal, or electrical stimulation. Because carbenes formed in this way can undergo rapid insertion into any nearby C-H, O-H or N-H bond, molecules that encode diazirine functions have emerged as privileged tools in applications ranging from biological target identification and proteomics through to polymer crosslinking and adhesion. Here we use a combination of experimental and computational methods to complete the first comprehensive survey of diazirine structure-function relationships, with a particular focus on thermal activation methods. We reveal a striking ability to vary the activation energy and activation temperature of aryl diazirines through the rational manipulation of electronic properties. Significantly, we show that electron-rich diazirines have greatly enhanced efficacy toward C-H insertion, under both thermal and photochemical activation conditions. We expect these results to lead to significant improvements in diazirine-based chemical probes and polymer crosslinkers.

Bimodal Evans-Polanyi Relationships in Hydrogen Atom Transfer from C(sp3)-H Bonds to the Cumyloxyl Radical. A Combined Time-Resolved Kinetic and Computational Study.

The applicability of the Evans-Polanyi (EP) relationship to HAT reactions from C(sp3)-H bonds to the cumyloxyl radical (CumO•) has been investigated. A consistent set of rate constants, kH, for HAT from the C-H bonds of 56 substrates to CumO•, spanning a range of more than 4 orders of magnitude, has been measured under identical experimental conditions. A corresponding set of consistent gas-phase C-H bond dissociation enthalpies (BDEs) spanning 27 kcal mol-1 has been calculated using the (RO)CBS-QB3 method. The log kH' vs C-H BDE plot shows two distinct EP relationships, one for substrates bearing benzylic and allylic C-H bonds (unsaturated group) and the other one, with a steeper slope, for saturated hydrocarbons, alcohols, ethers, diols, amines, and carbamates (saturated group), in line with the bimodal behavior observed previously in theoretical studies of reactions promoted by other HAT reagents. The parallel use of BDFEs instead of BDEs allows the transformation of this correlation into a linear free energy relationship, analyzed within the framework of the Marcus theory. The ΔG⧧HAT vs ΔG°HAT plot shows again distinct behaviors for the two groups. A good fit to the Marcus equation is observed only for the saturated group, with λ = 58 kcal mol-1, indicating that with the unsaturated group λ must increase with increasing driving force. Taken together these results provide a qualitative connection between Bernasconi's principle of nonperfect synchronization and Marcus theory and suggest that the observed bimodal behavior is a general feature in the reactions of oxygen-based HAT reagents with C(sp3)-H donors.

Flexible polyfluorinated bis-diazirines as molecular adhesives.

Motivated by a desire to develop flexible covalent adhesives that afford some of the same malleability in the adhesive layer as traditional polymer-based adhesives, we designed and synthesized two flexible, highly fluorinated bis-diazirines. Both molecules are shown to function as effective crosslinkers for polymer materials, and to act as strong adhesives when painted between two polymer objects of low surface energy, prior to thermal activation. Data obtained from lap-shear experiments suggests that greater molecular flexibility is correlated with improved mechanical compliance in the adhesive layer.

Computational Study of Hydrogen Bond Interactions in Water Cluster-Organic Molecule Complexes.

We analyzed the interactions present in complexes that acetone, azomethane, dimethylamine, dimethyl ether, methyl acetate, and oxirane form with 39 different (H2O)n clusters (n = 1-10). A random generation of configurations and a subsequent screening procedure were employed to sample representative interactions. Using quantum chemical computations, we calculated the associated binding energies, which range from -0.19 to -10.76 kcal/mol at the DLPNO-CCSD(T)/CBS level. It was found that the binding energies can be understood in terms of various factors, including the water cluster size, the nature of the organic molecule, and the type of hydrogen bond donor. We find that the most stable complexes often arise from a combination of a strong hydrogen bond plus a secondary interaction between the organic molecule and the water cluster.

Antioxidant activity of highly hydroxylated fullerene C60 and its interactions with the analogue of α-tocopherol.

Polyhydroxylated fullerenes (fullerenols) are excellent free radical scavengers. Despite the large number of reports on their reactions with reactive oxygen species, there is no report on their ability to trap lipid peroxyl radicals and act as chain-breaking antioxidants. In this work we studied the effect of fullerenol C60(OH)36 on the kinetics of peroxidation of polyunsaturated fatty acid ester (methyl linoleate) dispersed in two model systems that mimic biological systems: Triton X-100 micelles and Large Unilamellar Vesicles, at pH 4, 7 and 10. As a control antioxidant 2,2,5,7,8-pentamethyl-6-hydroxychroman (PMHC, an analog of α-tocopherol) was used. In micellar systems at pH 4.0, C60(OH)36 reacts with peroxyl radicals with kinh= (5.8 ± 0.3) × 103 M-1s-1 (for PMHC kinh = 22 × 103 M-1s-1). Surprisingly, at pH 7 a retardation instead of inhibition was recorded, and at pH 10 no effect on the kinetics of the process was observed. In liposomal systems fullerenol was not active at pH 4.0 but at pH 7.0 kinh = (8.8 ± 2.6) × 103 M-1s-1 for fullerenol was 30% lower than kinh for PMHC. Using two fluorescent probes we confirmed that at pH 7.4 fullerenol/fullerenol anions are incorporated into the phospholipid heads of the bilayer. We also studied the cooperation of C60(OH)36 with PMHC: both compounds seem to contribute their peroxyl radical trapping abilities independently at pH 4 whereas at pH 7 and 10 a hyper-synergy was observed. The antioxidant action of C60(OH)36 and its synergy with PMHC was also confirmed for peroxidation of human erythrocytes at pH 7.4. Assuming the simplified structural model of fullerenol limited to 36 hydroxyls as the only functional groups attached to C60 core we found by density-functional theory a low energy structure with OH groups distributed in the form of two polyhydroxyl regions separating two unsubstituted carbon regions with biphenyl-like structure. Our calculations indicate that abstraction of hydrogen atom from fullerenol by peroxyl or tocopheroxyl radical is endoergic. As the electron transfer from fullerenol polyanion to the radicals is also energetically disfavoured, the most probable mechanism of reaction with radicals is subsequent addition of peroxyl/tocopheroxyl radicals to biphenyl moieties surrounded by OH groups.

Reply to the 'Comment on "Extent of conjugation in diazonium-derived layers in molecular junction devices determined by experiment and modelling"' by R. L. McCreery, S. K. Saxena, M. Supur and U. Tefashe, Phys. Chem. Chem. Phys., 2020, 22, DOI: 10.1039/d0cp02412k.

Our paper [Phys. Chem. Chem. Phys., 2019, 21, 16762] is the subject of a comment that clarifies a flaw in analysis of STM data. We accept the comment in regard to the aspect ratio considerations, but we also further clarify the main conclusions of our paper, and provide a molecular scale schematic using the data presented in the comment to help refine the original conclusions. Taken together, this shows that models presented in the literature may benefit from including more fine structure details, as better understanding may emerge from such considerations. This was the intent of our original article, and we thank the comment authors for the chance to clarify these points.

Improved Basis-Set Incompleteness Potentials for Accurate Density-Functional Theory Calculations in Large Systems.

The accurate calculation of chemical properties using density-functional theory (DFT) requires the use of a nearly complete basis set. In chemical systems involving hundreds to thousands of atoms, the cost of the calculations place practical limitations on the number of basis functions that can be used. Therefore, in most practical applications of DFT to large systems, there exists a basis-set incompleteness error (BSIE). In this article, we present the next iteration of the basis-set incompleteness potentials (BSIPs), one-electron potentials designed to correct for basis-set incompleteness error. The ultimate goal associated with the development of BSIPs is to allow the calculation of molecular properties using DFT with near-complete-basis-set results at a computational cost that is similar to a small basis set calculation. In this work, we develop BSIPs for 10 atoms in the first and second rows (H, B-F, Si-Cl) and 15 common basis sets of the Pople, Dunning, Karlsruhe, and Huzinaga types. Our new BSIPs are constructed to minimize BSIE in the calculation of reaction energies, barrier heights, noncovalent binding energies, and intermolecular distances. The BSIPs were obtained using a training set of 15 944 data points. The fitting approach employed a regularized linear least-squares method with variable selection (the LASSO method), which results in a much better fit to the training data than our previous BSIPs while, at the same time, reducing the computational cost of BSIP development. The proposed BSIPs are tested on various benchmark sets and demonstrate excellent performance in practice. Our new BSIPs are also transferable; i.e., they can be used to correct BSIE in calculations that employ density functionals other than the one used in the BSIP development (B3LYP). Finally, BSIPs can be used in any quantum chemistry program that have implemented effective-core potentials without changes to the software.

Extent of conjugation in diazonium-derived layers in molecular junction devices determined by experiment and modelling.

This paper shows that molecular layers grown using diazonium chemistry on carbon surfaces have properties indicative of the presence of a variety of structural motifs. Molecular layers grown with aromatic monomers with thickness between 1 and ∼15 nm display optical absorption spectra with significant broadening but no change in band gap or onsets of absorption as a function of layer thickness. This suggests that there is no extended conjugation in these layers, contrary to the conclusions of previous work. Density-functional theory modelling of the non-conjugated versions of the constituent aromatic monomers reveals that the experimental trends in optical spectra can be recovered, thereby establishing limits to the degree of conjugation and the nature of the order of as-grown molecular layers. We conclude that the absence of both shifts in band gap and changes in absorption onset is a consequence of resonant conjugation within the layers being less than 1.5 monomer units, and that film disorder is the main origin of the optical spectra. These findings have important implications for understanding charge transport mechanisms in molecular junction devices, as the layers cannot be expected to behave as ideal, resonantly conjugated films, but should be viewed as a collection of mixed nonresonantly- and resonantly-conjugated monomers.

PEPCONF, a diverse data set of peptide conformational energies.

We present an extensive and diverse database of peptide conformational energies. Our database contains five different classes of model geometries: dipeptides, tripeptides, and disulfide-bridged, bioactive, and cyclic peptides. In total, the database consists of 3775 conformational energy data points and 4530 conformer geometries. All the reference energies have been calculated at the LC-ωPBE-XDM/aug-cc-pVTZ level of theory, which is shown to yield conformational energies with an accuracy in the order of tenths of a kcal/mol when compared to complete-basis-set coupled-cluster reference data. The peptide conformational data set (PEPCONF) is presented as a high-quality reference set for the development and benchmarking of molecular-mechanics and semi-empirical electronic structure methods, which are the most commonly used techniques in the modeling of medium to large proteins.

Evaluation of Polar Effects in Hydrogen Atom Transfer Reactions from Activated Phenols.

Evaluation of polar effects in hydrogen atom transfer (HAT) processes is made difficult by the fact that in most cases substrates characterized by lower bond dissociation energies (BDEs), activated from an enthalpic point of view, are also more activated by polar effects. In search of an exception to this general rule, we found that the introduction of a methoxy substituent in the 3-position of 2,6-dimethylphenol results in a small increase in the O-H BDE and a decrease of the ionization potential of the phenol. These findings suggest that the enthalpic effect associated with the addition of the m-methoxy group to 2,6-dimethylphenol will decrease reaction rates, while the polar effects will increase reaction rates. Our model analysis of polar effects has been experimentally validated by comparing the reactivity of 2,6-dimethylphenol with that of 2,6-dimethyl-3-methoxyphenol in HAT promoted by a series of radicals (cumyloxyl, galvinoxyl, 2,2-diphenylpycrylhydrazyl, phthalimide- N-oxyl, and benzotriazole- N-oxyl radicals). In line with our predictions, the ratio of HAT rate constants ( kH mOMe/ kHH) is larger in cases where there is a greater contribution of polar effects in the HAT reaction, i.e., in HAT promoted by N-oxyl radicals containing electron-withdrawing groups or when more polar solvents are employed.

Extremely Fast Hydrogen Atom Transfer between Nitroxides and HOO· Radicals and Implication for Catalytic Coantioxidant Systems.

We report a novel coantioxidant system based on TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical) that, in biologically relevant model systems, rapidly converts chain-carrying alkylperoxyl radicals to HOO·. Extremely efficient quenching of HOO· by TEMPO blocks the oxidative chain. Rate constants in chlorobenzene were measured to be 1.1 × 109 M-1 s-1 for the reductive reaction TEMPO + HOO· → TEMPOH + O2 and 5.0 × 107 M-1 s-1 for the oxidative reaction TEMPOH + HOO· → TEMPO + H2O2. These rate constants are significantly higher than that associated with the reaction of HOO· with α-tocopherol, Nature's best lipid soluble antioxidant ( k = 1.6 × 106 M-1 s-1). These data show that in the presence of ROO·-to-HOO· chain-transfer agents, which are common in lipophilic environments, the TEMPO/TEMPOH couple protects organic molecules from oxidation by establishing an efficient reductive catalytic cycle. This catalytic cycle provides a new understanding of the efficacy of the antioxidant capability of TEMPO in nonaqueous systems and its potential to act as a chemoprotective against radical damage.

Ab initio characterization of coupling strength for all types of dangling-bond pairs on the hydrogen-terminated Si(100)-2 × 1 surface.

Recent work has suggested that coupled silicon dangling bonds sharing an excess electron may serve as building blocks for quantum-cellular-automata cells and quantum computing schemes when constructed on hydrogen-terminated silicon surfaces. In this work, we employ ab initio density-functional theory to examine the details associated with the coupling between two dangling bonds sharing one excess electron and arranged in various configurations on models of phosphorous-doped hydrogen-terminated silicon (100) surfaces. Our results show that the coupling strength depends strongly on the relative orientation of the dangling bonds on the surface and on the separation between them. The orientation of dangling bonds is determined by the anisotropy of the silicon (100) surface, so this feature of the surface is a significant contributing factor to variations in the strength of coupling between dangling bonds. The results demonstrate that simple models for approximating tunneling, such as the Wentzel-Kramer-Brillouin method, which do not incorporate the details of surface structure, are incapable of providing reasonable estimates of tunneling rates between dangling bonds. The results provide guidance to efforts related to the development of dangling-bond based computing elements.