Assessment of the applicability of DFT methods to [Cp*Rh]-catalyzed hydrogen evolution processes.

The present computational study provides a benchmark of density functional theory (DFT) methods in describing hydrogen evolution processes catalyzed by [Cp*Rh]-containing organometallic complexes. A test set was composed of 26 elementary reactions featuring chemical transformations and bonding situations essential for the field, including the emerging concept of non-innocent Cp* behavior. Reference values were obtained from a highly accurate 3/4 complete basis set and 6/7 complete PNO space extrapolated DLPNO-CCSD(T) energies. The performance of lower-level extrapolation procedures was also assessed. We considered 84 density functionals (DF) (including 13 generalized gradient approximations (GGA), nine meta-GGAs, 33 hybrids, and 29 double-hybrids) and three composite methods (HF-3c, PBEh-3c, and r2SCAN-3c), combined with different types of dispersion corrections (D3(0), D3BJ, D4, and VV10). The most accurate approach is the PBE0-DH-D3BJ (MAD of 1.36 kcal mol-1) followed by TPSS0-D3BJ (MAD of 1.60 kcal mol-1). Low-cost r2SCAN-3c composite provides a less accurate but much faster alternative (MAD of 2.39 kcal mol-1). The widely used Minnesota-family M06-L, M06, and M06-2X DFs should be avoided (MADs of 3.70, 3.94, and 4.01 kcal mol-1, respectively).

Rebound or Cage Escape? The Role of the Rebound Barrier for the Reactivity of Non-Heme High-Valent FeIV =O Species.

Owing to their high reactivity and selectivity, variations in the spin ground state and a range of possible pathways, high-valent FeIV =O species are popular models with potential bioinspired applications. An interesting example of a structure-reactivity pattern is the detailed study with five nonheme amine-pyridine pentadentate ligand FeIV =O species, including N4py: [(L1 )FeIV =O]2+ (1), bntpen: [(L2 )FeIV =O]2+ (2), py2 tacn: [(L3 )FeIV =O]2+ (3), and two isomeric bispidine derivatives: [(L4 )FeIV =O]2+ (4) and [(L5 )FeIV =O]2+ (5). In this set, the order of increasing reactivity in the hydroxylation of cyclohexane differs from that with cyclohexadiene as substrate. A comprehensive DFT, ab initio CASSCF/NEVPT2 and DLPNO-CCSD(T) study is presented to untangle the observed patterns. These are well reproduced when both activation barriers for the C-H abstraction and the OH rebound are taken into account. An MO, NBO and deformation energy analysis reveals the importance of π(pyr) → π*xz (FeIII -OH) electron donation for weakening the FeIII -OH bond and thus reducing the rebound barrier. This requires that pyridine rings are oriented perpendicularly to the FeIII -OH bond and this is a subtle but crucial point in ligand design for non-heme iron alkane hydroxylation.

Exploration of Free Energy Surface of the Au10 Nanocluster at Finite Temperature.

The first step in comprehending the properties of Au10 clusters is understanding the lowest energy structure at low and high temperatures. Functional materials operate at finite temperatures; however, energy computations employing density functional theory (DFT) methodology are typically carried out at zero temperature, leaving many properties unexplored. This study explored the potential and free energy surface of the neutral Au10 nanocluster at a finite temperature, employing a genetic algorithm coupled with DFT and nanothermodynamics. Furthermore, we computed the thermal population and infrared Boltzmann spectrum at a finite temperature and compared it with the validated experimental data. Moreover, we performed the chemical bonding analysis using the quantum theory of atoms in molecules (QTAIM) approach and the adaptive natural density partitioning method (AdNDP) to shed light on the bonding of Au atoms in the low-energy structures. In the calculations, we take into consideration the relativistic effects through the zero-order regular approximation (ZORA), the dispersion through Grimme's dispersion with Becke-Johnson damping (D3BJ), and we employed nanothermodynamics to consider temperature contributions. Small Au clusters prefer the planar shape, and the transition from 2D to 3D could take place at atomic clusters consisting of ten atoms, which could be affected by temperature, relativistic effects, and dispersion. We analyzed the energetic ordering of structures calculated using DFT with ZORA and single-point energy calculation employing the DLPNO-CCSD(T) methodology. Our findings indicate that the planar lowest energy structure computed with DFT is not the lowest energy structure computed at the DLPN0-CCSD(T) level of theory. The computed thermal population indicates that the 2D elongated hexagon configuration strongly dominates at a temperature range of 50-800 K. Based on the thermal population, at a temperature of 100 K, the computed IR Boltzmann spectrum agrees with the experimental IR spectrum. The chemical bonding analysis on the lowest energy structure indicates that the cluster bond is due only to the electrons of the 6 s orbital, and the Au d orbitals do not participate in the bonding of this system.

Influence of the complete basis set approximation, tight weighted-core, and diffuse functions on the DLPNO-CCSD(T1) atomization energies of neutral H,C,O-compounds.

The impact of complete basis set extrapolation schemes (CBS), diffuse functions, and tight weighted-core functions on enthalpies of formation predicted via the DLPNO-CCSD(T1) reduced Feller-Peterson-Dixon approach has been examined for neutral H,C,O-compounds. All tested three-point (TZ/QZ/5Z) extrapolation schemes result in mean unsigned deviation (MUD) below 2 kJ mol-1 relative to the experiment. The two-point QZ/5Z and TZ/QZ CBS 1 / l max 3 extrapolation schemes are inferior to their inverse power counterpart ( 1 / l max + 1 / 2 4 ) by 1.3 and 4.3 kJ mol-1 . The CBS extrapolated frozen core atomization energies are insensitive (within 1 kJ mol-1 ) to augmentation of the basis set with tight weighted core functions. The core-valence correlation effects converge already at triple-ζ, although double-ζ/triple-ζ CBS extrapolation performs better and is recommended. The effect of diffuse function augmentation converges slowly, and cannot be reproduced with double- ζ or triple- ζ calculations as these are plagued with basis set superposition and incompleteness errors.

Theoretical elucidation of the structure, bonding, and reactivity of the CaMn4Ox clusters in the whole Kok cycle for water oxidation embedded in the oxygen evolving center of photosystem II. New molecular and quantum insights into the mechanism of the O-O bond formation.

This paper reviews our historical developments of broken-symmetry (BS) and beyond BS methods that are applicable for theoretical investigations of metalloenzymes such as OEC in PSII. The BS hybrid DFT (HDFT) calculations starting from high-resolution (HR) XRD structure in the most stable S1 state have been performed to elucidate structure and bonding of whole possible intermediates of the CaMn4Ox cluster (1) in the Si (i = 0 ~ 4) states of the Kok cycle. The large-scale HDFT/MM computations starting from HR XRD have been performed to elucidate biomolecular system structures which are crucial for examination of possible water inlet and proton release pathways for water oxidation in OEC of PSII. DLPNO CCSD(T0) computations have been performed for elucidation of scope and reliability of relative energies among the intermediates by HDFT. These computations combined with EXAFS, XRD, XFEL, and EPR experimental results have elucidated the structure, bonding, and reactivity of the key intermediates, which are indispensable for understanding and explanation of the mechanism of water oxidation in OEC of PSII. Interplay between theory and experiments have elucidated important roles of four degrees of freedom, spin, charge, orbital, and nuclear motion for understanding and explanation of the chemical reactivity of 1 embedded in protein matrix, indicating the participations of the Ca(H2O)n ion and tyrosine(Yz)-O radical as a one-electron acceptor for the O-O bond formation. The Ca-assisted Yz-coupled O-O bond formation mechanisms for water oxidation are consistent with recent XES and very recent time-resolved SFX XFEL and FTIR results.

Computational Study on Chemoselective Difunctionalization of Unactivated Alkenes with Radical-mediated Remote Functional Group Migration.

A computational study of the radical-mediated chemoselective difunctionalization of the tertiary alcohol substituted aliphatic alkenes is carried out employing density functional theory (DFT) and high-level coupled-cluster methods, such as coupled-cluster singles and doubles with perturbative triples [DLPNO-CCSD(T)]. Our results indicate that the cyclic vinyl radical plays an important role in the progression of the reactions. Our computations demonstrated that the chemoselective difunctionalization of unactivated alkenes with radical-mediated remote functional group migration is suitable for the 5- and 6-exo-dig cyclization, as opposite to 3- and 4-exo-dig cyclization suffering from cyclic intermediate with high energy. Our results show that the migration of nitrile group is more preferable than that of alkynyl group for the molecules including both cyano group and alkynyl group. For the 5- and 6-exo-dig cyclization, the rate-determining step is the homolysis of the C-C σ-bond in the cyclic intermediate, which results in the hydroxyl alkyl radical.

Unveiling the Noncovalent Interaction of Thiazol-2-ylidene and Its Derivatives as N-heterocyclic Carbene with Different Proton Donor Molecules.

The importance of noncovalent interaction has gained attention in various domains covering drug and novel catalyst design. The present study mainly characterizes the role of hydrogen bond (H-bond) and other intermolecular interactions in different (1 : 1) complex analogues formed between the N-aryl-thiazol-2-ylidene (YR) and five proton donor (HX) molecules. The analysis of the singlet-triplet energy gap ( Δ E S - T ${{\rm{\Delta }}E_{\left( {S - T} \right)} }$ ) confirmed the stability of the singlet state for this class of N-aryl-thiazol-2-ylidenes than the triplet state. The interaction energy values of the YR-HX complexes follow the order: YR-NH3

Conformational energies of reference organic molecules: benchmarking of common efficient computational methods against coupled cluster theory.

We selected 145 reference organic molecules that include model fragments used in computer-aided drug design. We calculated 158 conformational energies and barriers using force fields, with wide applicability in commercial and free softwares and extensive application on the calculation of conformational energies of organic molecules, e.g. the UFF and DREIDING force fields, the Allinger's force fields MM3-96, MM3-00, MM4-8, the MM2-91 clones MMX and MM+, the MMFF94 force field, MM4, ab initio Hartree-Fock (HF) theory with different basis sets, the standard density functional theory B3LYP, the second-order post-HF MP2 theory and the Domain-based Local Pair Natural Orbital Coupled Cluster DLPNO-CCSD(T) theory, with the latter used for accurate reference values. The data set of the organic molecules includes hydrocarbons, haloalkanes, conjugated compounds, and oxygen-, nitrogen-, phosphorus- and sulphur-containing compounds. We reviewed in detail the conformational aspects of these model organic molecules providing the current understanding of the steric and electronic factors that determine the stability of low energy conformers and the literature including previous experimental observations and calculated findings. While progress on the computer hardware allows the calculations of thousands of conformations for later use in drug design projects, this study is an update from previous classical studies that used, as reference values, experimental ones using a variety of methods and different environments. The lowest mean error against the DLPNO-CCSD(T) reference was calculated for MP2 (0.35 kcal mol-1), followed by B3LYP (0.69 kcal mol-1) and the HF theories (0.81-1.0 kcal mol-1). As regards the force fields, the lowest errors were observed for the Allinger's force fields MM3-00 (1.28 kcal mol-1), ΜΜ3-96 (1.40 kcal mol-1) and the Halgren's MMFF94 force field (1.30 kcal mol-1) and then for the MM2-91 clones MMX (1.77 kcal mol-1) and MM+ (2.01 kcal mol-1) and MM4 (2.05 kcal mol-1). The DREIDING (3.63 kcal mol-1) and UFF (3.77 kcal mol-1) force fields have the lowest performance. These model organic molecules we used are often present as fragments in drug-like molecules. The values calculated using DLPNO-CCSD(T) make up a valuable data set for further comparisons and for improved force field parameterization.

A DLPNO-CCSD(T) benchmarking study of intermolecular interactions of ionic liquids.

The accuracy of correlation energy recovered by coupled cluster single-, double-, and perturbative triple-excitations, CCSD(T), has led to the method being considered the gold standard of computational chemistry. The application of CCSD(T) has been limited to medium-sized molecular systems due to its steep scaling with molecular size. The recent development of alternative domain-based local pair natural orbital coupled-cluster method, DLPNO-CCSD(T), has significantly broadened the range of chemical systems to which CCSD(T) level calculations can be applied. Condensed systems such as ionic liquids (ILs) have a large contribution from London dispersion forces of up to 150 kJ mol-1 in large-scale clusters. Ionic liquids show appreciable charge transfer effects that result in the increased valence orbital delocalization over the entire ionic network, raising the question whether the application of methods based on localized orbitals is reliable for these semi-Coulombic materials. Here the performance of DLPNO-CCSD(T) is validated for the prediction of correlation interaction energies of two data sets incorporating single-ion pairs of protic and aprotic ILs. DLPNO-CCSD(T) produced results within chemical accuracy with tight parameter settings and a non-iterative treatment of triple excitations. To achieve spectroscopic accuracy of 1 kJ mol-1 , especially for hydrogen-bonded ILs and those containing halides, the DLPNO settings had to be increased by two orders of magnitude and include the iterative treatment of triple excitations, resulting in a 2.5-fold increase in computational cost. Two new sets of parameters are put forward to produce the performance of DLPNO-CCSD(T) within chemical and spectroscopic accuracy.

Assessment of DLPNO-CCSD(T)-F12 and its use for the formulation of the low-cost and reliable L-W1X composite method.

In the present study, we have investigated the performance of RIJCOSX DLPNO-CCSD(T)-F12 methods for a wide range of systems. Calculations with a high-accuracy option ["DefGrid3 RIJCOSX DLPNO-CCSD(T1 )-F12"] extrapolated to the complete-basis-set limit using the maug-cc-pV[D+d,T+d]Z basis sets provides fairly good agreements with the canonical CCSD(T)/CBS reference for a diverse set of thermochemical and kinetic properties [with mean absolute deviations (MADs) of ~1-2 kJ mol-1 except for atomization energies]. On the other hand, the low-cost "RIJCOSX DLPNO-CCSD(T)-F12D" option leads to substantial deviations for certain properties, notably atomization energies (MADs of up to tens of kJ mol-1 ). With the high-accuracy CBS approach, we have formulated the L-W1X method, which further includes a low-cost core-valence plus scalar-relativistic term. It shows generally good accuracy. For improved accuracies in specific cases, we advise replacing maug-cc-pV(n+d)Z with jun-cc-pV(n+d)Z for the calculation of electron affinities, and using well-constructed isodesmic-type reactions to obtain atomization energies. For medium-sized systems, DefGrid3 RIJCOSX DLPNO-CCSD(T1 )-F12 calculations are several times faster than the corresponding canonical computation; the use of the local approximations (RIJCOSX and DLPNO) leads to a better scaling than that for the canonical calculation (from ~6-7 down to ~2-4 for our test systems). Thus, the DefGrid3 RIJCOSX DLPNO-CCSD(T1 )-F12 method, and the L-W1X protocol that based on it, represent a useful means for obtaining accurate thermochemical quantities for larger systems.

Improved Estimates of Host-Guest Interaction Energies for Endohedral Fullerenes Containing Rare Gas Atoms, Small Molecules, and Cations.

Endohedral fullerenes have evinced much interest from the fundamental and applications points of view. However, given the nature of the weak interaction between the guest species and the host cage in these confined systems, the interaction energy values obtained using various theoretical methods, and different basis sets vary over a wide range. For example, the reported interaction energy for the HF@C60 system ranges from -2.5 kcal/mol to -14.9 kcal/mol. In the present manuscript, we report reliable interaction energy values for different endohedral fullerenes (He@C60 , Ne@C60 , Ar@C60 , Kr@C60 , H2 @C60 , HF@C60 , H2 O@C60 , NH3 @C60 , CH4 @C60 , Li+ @C60 , Na+ @C60 , and K+ @C60 ) obtained using the domain-based local pair natural orbital coupled-cluster singles, doubles, and perturbative triples (DLPNO-CCSD(T)) method and the def2-TZVP basis set. We believe that these energy values could be considered as benchmark values, and the performance of other quantum chemical methods could be assessed accordingly. Local energy decomposition analysis within the DLPNO-CCSD(T) framework is used to estimate the electrostatic, exchange, and dispersion components of the interaction energy for some of the endohedral fullerenes.

Supramolecular Diversity, Theoretical Investigation and Antibacterial Activity of Cu, Co and Cd Complexes Based on the Tridentate N,N,O-Schiff Base Ligand Formed In Situ.

The four new complexes, [Cu(HL1)(L2)Cl] (1), [Cu(HL1)(L1)]∙Cl∙2H2O (2), [Co(L1)2]∙Cl (3) and [Cd(HL1)I2]∙dmso (4), have been prepared by one-pot reactions of the respective chloride or iodide metal salt with a non-aqueous solution of the polydentate Schiff base, HL1, resulted from in situ condensation of benzhydrazide and 2-pyridinecarboxaldehyde, while a ligand HL2, in case of 1, has been formed due to the oxidation of 2-pyridinecarboxaldehyde under reaction conditions. The crystallographic analysis revealed that the molecular building units in 1-4 are linked together into complex structures by hydrogen bonding, resulting in 1D, 2D and 3D supramolecular architectures for 1, 2 and 4, respectively, and the supramolecular trimer for 3. The electronic structures of 1-4 were investigated by the DFT theoretical calculations. The non-covalent interactions in the crystal structures of 1-4 were studied by means of the Hirshfeld surface analysis and the QTAIM theory with a special focus on the C-H⋯Cl bonding. From the DFT/DLPNO-CCSD(T) calculations, using a series of charged model {R3C-H}0⋯Cl- assemblies, we propose linear regressions for assessment of the interaction enthalpy (ΔH, kcal mol-1) and the binding energy (BE, kcal mol-1) between {R3C-H}0 and Cl- sites starting from the electron density at the bond critical point (ρ(rBCP), a.u.): ΔH = -678 × ρ(r) + 3 and BE = -726 × ρ(r) + 4. It was also has been found that compounds 1, 3 and 4 during in vitro screening showed an antibacterial activity toward the nine bacteria species, comprising both Gram-positive and Gram-negative, with MIC values ranging from 156.2 to 625 mg/L. The best results have been obtained against Acinetobacter baumannii MßL.

Antiradical Properties of N-Oxide Surfactants-Two in One.

Surfactants are molecules that lower surface or interfacial tension, and thus they are broadly used as detergents, wetting agents, emulsifiers, foaming agents, or dispersants. However, for modern applications, substances that can perform more than one function are desired. In this study we evaluated antioxidant properties of two homological series of N-oxide surfactants: monocephalic 3-(alkanoylamino)propyldimethylamine-N-oxides and dicephalic N,N-bis[3,3'-(dimethylamino)propyl]alkylamide di-N-oxides. Their antiradical properties were tested against stable radicals using electron paramagnetic resonance (EPR) and UV-vis spectroscopy. The experimental investigation was supported by theoretical density functional theory (DFT) and ab initio modeling of the X-H bonds dissociation enthalpies, ionization potentials, and Gibbs free energies for radical scavenging reactions. The evaluation was supplemented with a study of biological activity. We found that the mono- and di-N-oxides are capable of scavenging reactive radicals; however, the dicephalic surfactants are more efficient than their linear analogues.

DFT, DLPNO-CCSD(T), and NEVPT2 benchmark study of the reaction between ferrocenium and trimethylphosphine.

The reaction between ferrocenium and trimethylphosphine was studied using density functional theory (DFT), domain-based local pair natural orbital coupled cluster theory with single-, double-, and perturbative triple excitations (DLPNO-CCSD(T)), and N-electron valence state perturbation theory (NEVPT2). The accuracy of the DFT functionals decreases compared to the DLPNO-CCSD(T) level in the following order: M06-L > TPSS > M06, BLYP > PBE, PBE0, B3LYP > > PWPB95 > > DSD-BLYP. The roles of thermochemical, continuum solvation (SMD), and counterpoise corrections were evaluated. Grimme's D3 empirical dispersion correction is essential for all functionals studied except M06 and M06-L. The reliability of the frequency calculations performed directly within the SMD was confirmed. The systems showed no significant multireference character according to T1 and T2 diagnostics and the fractional occupation number (FOD) weighted electron density analysis. The multireference NEVPT2 calculations gave qualitatively valid conclusions about the reaction mechanism. However, a multireference approach is generally not recommended because it requires arbitrary chosen active spaces.

Assessing the validity of DLPNO-CCSD(T) in the calculation of activation and reaction energies of ubiquitous enzymatic reactions.

The domain-based local pair natural orbital coupled-cluster with single, double, and perturbative triples excitation (DLPNO-CCSD(T)) method was employed to portray the activation and reaction energies of four ubiquitous enzymatic reactions, and its performance was confronted to CCSD(T)/complete basis set (CBS) to assess its accuracy and robustness in this specific field. The DLPNO-CCSD(T) results were also confronted to those of a set of density functionals (DFs) to understand the benefit of implementing this technique in enzymatic quantum mechanics/molecular mechanics (QM/MM) calculations as a second QM component, which is often treated with DF theory (DFT). On average, the DLPNO-CCSD(T)/aug-cc-pVTZ results were 0.51 kcal·mol-1 apart from the canonic CCSD(T)/CBS, without noticeable biases toward any of the reactions under study. All DFs fell short to the DLPNO-CCSD(T), both in terms of accuracy and robustness, which suggests that this method is advantageous to characterize enzymatic reactions and that its use in QM/MM calculations, either alone or in conjugation with DFT, in a two-region QM layer (DLPNO-CCSD(T):DFT), should enhance the quality and faithfulness of the results.

Toward a less costly but accurate calculation of the CCSD(T)/CBS noncovalent interaction energy.

The popular method of calculating the noncovalent interaction energies at the coupled-cluster single-, double-, and perturbative triple-excitations [CCSD(T)] theory level in the complete basis set (CBS) limit was to add a CCSD(T) correction term to the CBS second-order Møller-Plesset perturbation theory (MP2). The CCSD(T) correction term is the difference between the CCSD(T) and MP2 interaction energies evaluated in a medium basis set. However, the CCSD(T) calculations with the medium basis sets are still very expensive for systems with more than 30 atoms. Comparatively, the domain-based local pair natural orbital coupled-cluster method [DLPNO-CCSD(T)] can be applied to large systems with over 1,000 atoms. Considering both the computational accuracy and efficiency, in this work, we propose a new scheme to calculate the CCSD(T)/CBS interaction energies. In this scheme, the MP2/CBS term keeps intact and the CCSD(T) correction term is replaced by a DLPNO-CCSD(T) correction term which is the difference between the DLPNO-CCSD(T) and DLPNO-MP2 interaction energies evaluated in a medium basis set. The interaction energies of the noncovalent systems in the S22, HSG, HBC6, NBC10, and S66 databases were recalculated employing this new scheme. The consistent and tight settings of the truncation parameters for DLPNO-CCSD(T) and DLPNO-MP2 in this noncanonical CCSD(T)/CBS calculations lead to the maximum absolute deviation and root-mean-square deviation from the canonical CCSD(T)/CBS interaction energies of less than or equal to 0.28 kcal/mol and 0.09 kcal/mol, respectively. The high accuracy and low cost of this new computational scheme make it an excellent candidate for the study of large noncovalent systems.

Accurate prediction of norbornadiene cycle enthalpies by DLPNO-CCSD(T1 )/CBS method.

The DLPNO-CCSD(T1 )/CBS method combined with simple reactions containing small reference species leads to an improvement in the accuracy of theoretically evaluated enthalpies of formation of medium-sized polyalicyclic hydrocarbons when compared with the widely used composite approach. The efficiency of the DLPNO-CCSD(T1 )/CBS method is most vividly demonstrated by comparing with the results of G4 calculations for adamantane. The most important factor in choosing appropriate working reaction is the same number of species on both sides of the equation. Among these reactions, the reactions with small enthalpy change usually provide a better cancellation of errors. The DLPNO-CCSD(T1 )/CBS method was used to calculate the enthalpies of formation of compounds belonging to the norbornadiene cycle (norbornadiene, quadricyclane, norbornene, nortricyclane, and norbornane). The most reliable experimental enthalpies of formation are recommended for these compounds by comparing calculated values with conflicting experimental data.

Superhalogen and Superacid.

A superhalogen F@C20 (CN)20 and a corresponding Brønsted superacid were designed and investigated on DFT and DLPNO-CCSD(T) levels of theory. Calculated compounds have outstanding electron affinity and deprotonation energy, respectively. We consider superacid H[F@C20 (CN)20 ] to be able to protonate molecular nitrogen. The stability of these structures is discussed, while some of the previous predictions concerning neutral Brønsted superacids of record strength are doubted. © 2019 Wiley Periodicals, Inc.

Generalized Prediction of Enthalpies of Formation Using DLPNO-CCSD(T) Ab Initio Calculations for Molecules Containing the Elements H, C, N, O, F, S, Cl, Br.

The prediction of thermochemical properties such as enthalpies of formation is of crucial importance, both in research and industrial applications, especially for systems involving not well-characterized molecules, such as biomass systems (bio-oils), or systems involving new compounds (new-generation refrigerants). It is highly desirable to obtain an efficient method by which these values can be predicted. Ab initio-based calculations can be very accurate for predicting gas phase thermochemical properties and are usually more versatile than group contribution methods. In this work, we propose a general extension of the work of Paulechka and Kazakov, using very accurate and efficient domain-based local pair natural orbital-coupled cluster theory ab initio calculations, to determine the enthalpies of formation of a broad variety of molecules. New sets of regressed atomic contributions are proposed for a larger group of elements: H, C, N, O, F, S, Cl, and Br. Excellent predictions are obtained for the most studied compounds (bio-oil compounds and refrigerants). © 2019 Wiley Periodicals, Inc.

A Robust and Cost-Efficient Scheme for Accurate Conformational Energies of Organic Molecules.

Several standard semiempirical methods as well as the MMFF94 force field approximation have been tested in reproducing 8 DLPNO-CCSD(T)/cc-pVTZ level conformational energies and spatial structures for 37 organic molecules representing pharmaceuticals, drugs, catalysts, synthetic precursors, industry-related chemicals (37conf8 database). All contemporary semiempirical methods surpass their standard counterparts resulting in more reliable conformational energies and spatial structures, even though at significantly higher computational costs. However, even these methods show unexpected failures in reproducing energy differences between several conformers of the crown ether 1,4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6). Inexpensive force field MMFF94 approximation groups with contemporary semiempirical methods in reproducing the correct order of conformational energies and spatial structures, although the performance in predicting absolute conformational energies compares to standard semiempirical methods. Based on these findings, we suggest a two-step strategy for reliable yet feasible conformational search and sampling in realistic-size flexible organic molecules: i) geometry optimization/preselection of relevant conformers using the MMFF94 force field; ii) single-point energy evaluations using a contemporary semiempirical method. We expect that developed database 37conf8 is going to be useful for development of semiempirical methods.