Dimers In Gas Phase Research Articles

Intersystem Crossings Drive Atmospheric Gas-Phase Dimer Formation.

High molecular weight "ROOR'" dimers, likely formed in the gas phase through self- and cross-reactions of complex peroxy radicals (RO2), have been suggested to play a key role in forming ultrafine aerosol particles in the atmosphere. However, the molecular-level reaction mechanism producing these dimers remains unknown. Using multireference quantum chemical methods, we explore one potentially competitive pathway for ROOR' production, involving the initial formation of triplet alkoxy radical (RO) pairs, followed by extremely rapid intersystem crossings (ISC) to the singlet surface, permitting subsequent recombination to ROOR'. Using CH3OO + CH3OO as a model system, we show that the initial steps of this reaction mechanism are likely to be very fast, as the transition states for both the formation and the decomposition of the CH3O4CH3 tetroxide intermediate are far below the reactants in energy. Next, we compute ISC rates for seven different atmospherically relevant 3(RO···R'O) complexes. The ISC rates vary significantly depending on the conformation of the complex and also exhibit strong stereoselectivity. Furthermore, the fastest ISC process is usually not between the lowest-energy triplet and singlet states but between the triplet ground state and an exited singlet state. For each studied (RO···R'O) system, at least one low-energy conformer with an ISC rate above 108 s-1 can be found. This demonstrates that gas-phase dimer formation in the atmosphere very likely involves ISCs originating in relativistic quantum mechanics.

Quantitative constraints on autoxidation and dimer formation from direct probing of monoterpene-derived peroxy radical chemistry

Organic peroxy radicals (RO2) are key intermediates in the atmospheric degradation of organic matter and fuel combustion, but to date, few direct studies of specific RO2 in complex reaction systems exist, leading to large gaps in our understanding of their fate. We show, using direct, speciated measurements of a suite of RO2 and gas-phase dimers from O3-initiated oxidation of α-pinene, that ∼150 gaseous dimers (C16-20H24-34O4-13) are primarily formed through RO2 cross-reactions, with a typical rate constant of 0.75-2 × 10-12 cm3 molecule-1 s-1 and a lower-limit dimer formation branching ratio of 4%. These findings imply a gaseous dimer yield that varies strongly with nitric oxide (NO) concentrations, of at least 0.2-2.5% by mole (0.5-6.6% by mass) for conditions typical of forested regions with low to moderate anthropogenic influence (i.e., ≤50-parts per trillion NO). Given their very low volatility, the gaseous C16-20 dimers provide a potentially important organic medium for initial particle formation, and alone can explain 5-60% of α-pinene secondary organic aerosol mass yields measured at atmospherically relevant particle mass loadings. The responses of RO2, dimers, and highly oxygenated multifunctional compounds (HOM) to reacted α-pinene concentration and NO imply that an average ∼20% of primary α-pinene RO2 from OH reaction and 10% from ozonolysis autoxidize at 3-10 s-1 and ≥1 s-1, respectively, confirming both oxidation pathways produce HOM efficiently, even at higher NO concentrations typical of urban areas. Thus, gas-phase dimer formation and RO2 autoxidation are ubiquitous sources of low-volatility organic compounds capable of driving atmospheric particle formation and growth.

Femtosecond laser induced Coulomb explosion imaging of aligned OCS oligomers inside helium nanodroplets.

Dimers and trimers of carbonyl sulfide (OCS) molecules embedded in helium nanodroplets are aligned by a linearly polarized 160 ps long moderately intense laser pulse and Coulomb exploded with an intense 40 fs long probe pulse in order to determine their structures. For the dimer, recording of 2D images of OCS+ and S+ ions and covariance analysis of the emission directions of the ions allow us to conclude that the structure is a slipped-parallel shape similar to the structure found for gas phase dimers. For the trimer, the OCS+ ion images and the corresponding covariance maps reveal the presence of a barrel-shaped structure (as in the gas phase) but also other structures not present in the gas phase, most notably a linear chain structure.

Non-Covalent Interactions in Molecular Crystals: Exploring the Accuracy of the Exchange-Hole Dipole Moment Model with Local Orbitals.

We present the first implementation of the exchange-hole dipole moment (XDM) model in combination with a numerical finite-support local orbital method (the SIESTA method) for the modeling of non-covalent interactions in periodic solids. The XDM model is parametrized for both the B86bPBE and PBE functionals using double-ζ- and triple-ζ-quality basis sets (DZP and TZP). The use of finite-support local orbitals is shown to have minimal impact on the computed dispersion coefficients for van der Waals molecular dimers and small molecular solids. However, the quality of the basis set affects the accuracy of calculated dimer binding energies and molecular-crystal lattice energies quite significantly; the size of the counterpoise correction indicates that this is caused by basis-set incompleteness error. In the case of the DZP basis set, its performance for weakly bound gas-phase dimers is similar to that of a double-ζ Gaussian basis set without diffuse functions. The new XDM implementation was tested on graphite and phosphorene exfoliation, and on the X23 benchmark set of molecular-crystal lattice energies. Our results indicate that lattice energies similar to plane-wave calculations can be obtained only if the counterpoise correction is applied. Alternatively, the calculated equilibrium geometries are reasonably close to the plane-wave equivalents, and composite approaches in which a single-point plane-wave calculation is used at the XDM/DZP equilibrium geometry yield good accuracy at a significantly lower computational cost.

Non-covalent interactions across organic and biological subsets of chemical space: Physics-based potentials parametrized from machine learning.

Classical intermolecular potentials typically require an extensive parametrization procedure for any new compound considered. To do away with prior parametrization, we propose a combination of physics-based potentials with machine learning (ML), coined IPML, which is transferable across small neutral organic and biologically relevant molecules. ML models provide on-the-fly predictions for environment-dependent local atomic properties: electrostatic multipole coefficients (significant error reduction compared to previously reported), the population and decay rate of valence atomic densities, and polarizabilities across conformations and chemical compositions of H, C, N, and O atoms. These parameters enable accurate calculations of intermolecular contributions-electrostatics, charge penetration, repulsion, induction/polarization, and many-body dispersion. Unlike other potentials, this model is transferable in its ability to handle new molecules and conformations without explicit prior parametrization: All local atomic properties are predicted from ML, leaving only eight global parameters-optimized once and for all across compounds. We validate IPML on various gas-phase dimers at and away from equilibrium separation, where we obtain mean absolute errors between 0.4 and 0.7 kcal/mol for several chemically and conformationally diverse datasets representative of non-covalent interactions in biologically relevant molecules. We further focus on hydrogen-bonded complexes-essential but challenging due to their directional nature-where datasets of DNA base pairs and amino acids yield an extremely encouraging 1.4 kcal/mol error. Finally, and as a first look, we consider IPML for denser systems: water clusters, supramolecular host-guest complexes, and the benzene crystal.

Quantum Chemical Calculations of Monomer-Dimer Equilibria of Aromatic C-Nitroso Compounds.

Monomer-dimer equilibria of nitrosobenzene and 2-nitrosopyridine in gas phase and solution were studied by range of quantum chemical methods in an attempt to find the level of theory suitable for modeling dimerization reactions of aromatic C-nitroso compounds in general. The best agreement with the experimental standard reaction Gibbs energies was obtained with a combination of double-hybrid density functionals B2PLYP-D3, PBE0DH, and DSD-PBEB86, and basis sets of triple-ζ quality. Of all other tested functionals, global hybrid PBE0 behaved equally well, and proved to be more than adequate for at least preliminary work. Other tested methods either produced inferior results (MP2, MP4(SDQ), CCSD, G4(MP2), CBS-QBS, CBS-APNO), or were too demanding for practical use (CCSD(T)). Analysis of computationally obtained thermodynamic data reveal intricate details of these reactions. Both E- and Z-dimers have several different conformers, which all have different solvation energies. While in the gas phase the nitrosobenzene E-dimer is more stable that its Z-form, in chloroform, the Z-form is more stable. Gas-phase dimerization entropies are large and negative, so these reactions are strongly temperature dependent. In some cases, like with 2-nitrosopyridines, entropy and enthalpy terms essentially cancel each other out, allowing structural and media effects to significantly influence dimerization equilibria.

Understanding the effects of packing and chemical terminations on the optical excitations of azobenzene-functionalized self-assembled monolayers

In a first-principles study based on many-body perturbation theory, we analyze the optical excitations of azobenzene-functionalized self-assembled monolayers (SAMs) with increasing packing density and different terminations, considering for comparison the corresponding gas-phase molecules and dimers. Intermolecular coupling increases with the density of the chromophores independently of the functional groups. The intense resonance that triggers photo-isomerization is present in the spectra of isolated dimers and diluted SAMs, but it is almost completely washed out in tightly packed architectures. Intermolecular coupling is partially inhibited by mixing differently functionalized azobenzene derivatives, in particular when large groups are involved. In this way, the excitation band inducing the photo-isomerization process is partially preserved and the effects of dense packing partly counterbalanced. Our results suggest that a tailored design of azobenzene-functionalized SAMs which optimizes the interplay between the packing density of the chromophores and their termination can lead to significant improvements in the photo-switching efficiency of these systems.

Noncovalent Halogen Bonding as a Mechanism for Gas-Phase Clustering.

Gas-phase clustering of nonionizable iodylbenzene (PhIO2) is attributed to supramolecular halogen bonding. Electrospray ionization results in the formation of ions of proton-charged and preferably sodium-charged clusters assignable to [H(PhIO2) n ]+, n = 1-7; [Na(PhIO2) n ]+, n = 1-6; [Na2(PhIO2) n ]2+, n = 7-20; [HNa(PhIO2) n ]2+, n = 6-19; [HNa2(PhIO2) n ]3+, n = 15-30; and [Na3(PhIO2) n ]3+, n = 14-30. The largest cluster detected has a supramolecular mass of 7147 Da. Electronic structure calculations using the M06-2X functional with the 6-311++G(d,p) basis set for C, H, and O, and LANL2DZ basis set for I and Na predict 298 K binding enthalpies for the protonated and sodiated iodylbenzene dimers and trimers are greater than 180 kJ/mol. This is exceptionally high in comparison with other protonated and sodiated clusters with well-established binding enthalpies. Strongly halogen-bonded motifs found in the crystalline phases of PhIO2 and its derivatives serve as models for the structures of larger gas-phase clusters, and calculations on simple model gas-phase dimer and trimer clusters result in similar motifs. This is the first account of halogen bonding playing an extensive role in gas-phase associations. Graphical Abstract ᅟ.

Theoretical Study of Acetic Acid Association Based on Hydrogen Bonding Mechanism.

Combining molecular dynamics (MD) and quantum chemistry (QM) simulation, the association mechanisms of acetic acid (AA) systems were examined. DFT methods were proposed to compare the hydrogen-bonding energies of variable acetic acid dimers and definitely provided the stable dimers configuration. Geometry parameters of dimers were also obtained by QM calculations, which were taken as the characteristic criteria for further MD analysis. Proportion of different acetic acid dimers in gas phase was obtained by Radial distribution function (RDF) analysis, and cyclic dimer with two O1-Ho hydrogen bonds was demonstrated as the most stable structure. While in the more complex liquid phase, the linear chain form was proved to be the most stable one. Furthermore, in the acetic acid-crotonaldehyde solution, the association configuration of acetic acid changed from the linear chain form to the cyclic dimer structure as the acetic acid concentration decreased gradually. This result would be significant for the chemical separation process of acetic acid-crotonaldehyde solutions.

London Dispersion Enables the Shortest Intermolecular Hydrocarbon H···H Contact.

Neutron diffraction of tri(3,5-tert-butylphenyl)methane at 20 K reveals an intermolecular C-H···H-C distance of only 1.566(5) Å, which is the shortest reported to date. The compound crystallizes as a C3-symmetric dimer in an unusual head-to-head fashion. Quantum chemical computations of the solid state at the HSE-3c level of theory reproduce the structure and the close contact well (1.555 Å at 0 K) and emphasize the significance of packing effects; the gas-phase dimer structure at the same level shows a 1.634 Å C-H···H-C distance. Intermolecular London dispersion interactions between contacting tert-butyl substituents surrounding the central contact deliver the decisive energetic contributions to enable this remarkable bonding situation.

Vibrational spectroscopy of the mass-selected tetrahydrofurfuryl alcohol monomers and its dimers in gas phase using IR depletion and VUV single photon ionization

Tetrahydrofurfuryl alcohol (THFA, C5H10O2) is a close chemical analog of the sugar rings present in the phosphate-deoxyribose backbone structure of the nucleic acids. In present report, the infrared (IR) spectra of the size-selected THFA monomer and its dimer have been investigated in a pulsed supersonic jet using infrared-vacuum ultraviolet (VUV) ionization. Herein, the laser light at 118nm wavelength served as the source of “soft” ionization in a time-of-flight mass spectrometer. The IR features for the monomers located at 3622cm−1 can be assigned to the intramolecular hydrogen bonding stretch vibrations mainly referring to A and C conformers. Compared with the monomer, however, characteristic peaks for the dimer centered at 3415 and 3453cm−1, red shifted 207 and 169cm−1, respectively, were associated with the intermolecular hydrogen bonding stretch vibrations. Combined with the quantum-chemical calculations, the dimer in the gas phase preferred cyclic AC conformer stabled by forming two strong intermolecular hydrogen bonds, which shown the high hydrogen bond selectivity in the cluster. The conclusions drawn from the role played in the conformational flexibility by the hydroxyl and ether groups may be extended to other biomolecules.

Experimental and Theoretical Investigation of Sodiated Multimers of Steroid Epimers with Ion Mobility-Mass Spectrometry.

Ion mobility-mass spectrometry (IM-MS) has recently seen increased use in the analysis of small molecules, especially in the field of metabolomics, for increased breadth of information and improved separation of isomers. In this study, steroid epimers androsterone and trans-androsterone were analyzed with IM-MS to investigate differences in their relative mobilities. Although sodiated monomers exhibited very similar collision cross-sections (CCS), baseline separation was observed for the sodiated dimer species (RS = 1.81), with measured CCS of 242.6 and 256.3 Å2, respectively. Theoretical modeling was performed to determine the most energetically stable structures of solution-phase and gas-phase monomer and dimer structures. It was revealed that these epimers differ in their preferred dimer binding mode in solution phase: androsterone adopts a R=O - Na+ - OH-R' configuration, whereas trans-androsterone adopts a R=O - Na+ - O=R' configuration. This difference contributes to a significant structural variation, and subsequent CCS calculations based on these structures relaxed in the gas phase were in agreement with experimentally measured values (ΔCCS ~ 5%). Additionally, these calculations accurately predicted the relative difference in mobility between the epimers. This study illustrates the power of combining experimental and theoretical results to better elucidate gas-phase structures. Graphical Abstract ᅟ.

Hydrogen-Bonding Polarizable Intermolecular Potential Model for Water.

A polarizable intermolecular potential model with short-range directional hydrogen-bonding interactions was developed for water. The model has a rigid geometry, with bond lengths and angles set to experimental gas-phase values. Dispersion interactions are represented by the Buckingham potential assigned to the oxygen atom, whereas electrostatic interactions are modeled by Gaussian charges. Polarization is handled by a Drude oscillator site, using a negative Gaussian charge attached to the oxygen atom by a harmonic spring. An explicit hydrogen-bonding term is included in the model to account for the effects of charge transfer. The model parameters were optimized to density, configurational energy, pair correlation function, and the dielectric constant of water under ambient conditions, as well as the minimum gas-phase dimer energy. Molecular dynamics and Gibbs ensemble Monte Carlo simulations were performed to evaluate the new model with respect to the thermodynamic and transport properties over a wide range of temperature and pressure conditions. Good agreement between model predictions and experimental data was found for most of the properties studied. The new model yields better performance relative to the majority of existing models and outperforms the BK3 model, which is one of the best polarizable models, for vapor-liquid equilibrium properties, whereas the new model is not better than the BK3 model for representation of other properties. The model can be efficiently simulated with the thermalized Drude oscillator algorithm, resulting in computational costs only 3 times higher than those of the nonpolarizable TIP4P/2005 model, whereas having significantly improved properties. Because it involves only a single Drude oscillator site, the new model is significantly faster than polarizable models with multiple sites. With the explicit inclusion of hydrogen-bond interactions, the model may provide a better description of the phase behavior of aqueous mixtures.

Infrared Action Spectroscopy of Low-Temperature Neutral Gas-Phase Molecules of Arbitrary Structure.

We demonstrate a technique for IR action spectroscopy that enables measuring IR spectra in a background-free fashion for low-temperature neutral gas-phase molecules of arbitrary structure. The method is exemplified experimentally for N-methylacetamide molecules in the mid-IR spectral range of 1000-1800 cm^{-1}, utilizing the free electron laser FELIX. The technique involves the resonant absorption of multiple mid-IR photons, which induces molecular dissociation. The dissociation products are probed with 10.49eV vacuum ultraviolet photons and analyzed with a mass spectrometer. We also demonstrate the capability of this method to record, with unprecedented ease, mid-IR spectra for the molecular associates, such as clusters and oligomers, present in a molecular beam. In this way the mass-selected spectra of low-temperature gas-phase dimers and trimers of N-methylacetamide are measured in the full amide I-III range.

Geometry of an Isolated Dimer of Imidazole Characterised by Rotational Spectroscopy and Ab Initio Calculations.

An isolated, gas-phase dimer of imidazole is generated through laser vaporisation of a solid rod containing a 1:1 mixture of imidazole and copper in the presence of an argon buffer gas undergoing supersonic expansion. The complex is characterised through broadband rotational spectroscopy and is shown to have a twisted, hydrogen-bonded geometry. Calculations at the CCSD(T)(F12*)/cc-pVDZ-F12 level of theory confirm this to be the lowest-energy conformer of the imidazole dimer. The distance between the respective centres of mass of the imidazole monomer subunits is determined to be 5.2751(1) Å, and the twist angle γ describing rotation of one monomer with respect to the other about a line connecting the centres of mass of the monomers is determined to be 87.9(4)°. Four out of six intermolecular parameters in the model geometry are precisely determined from the experimental rotational constants and are consistent with results calculated ab initio.

Gas-Phase Dimerization of Ethylene under Mild Conditions Catalyzed by MOF Materials Containing (bpy)NiII Complexes

NU-1000-(bpy)NiII, a highly porous MOF material possessing well-defined (bpy)NiII moieties, was prepared through solvent-assisted ligand incorporation (SALI). Treatment with Et2AlCl affords a single-site catalyst with excellent catalytic activity for ethylene dimerization (intrinsic activity for butenes that is up to an order of magnitude higher than the corresponding (bpy)NiCl2 homogeneous analogue) and stability (can be reused at least three times). The high porosity of this catalyst results in outstanding levels of activity at ambient temperature in gas-phase ethylene dimerization reactions, both under batch and continuous flow conditions.

Stacking of the mutagenic base analogue 5-bromouracil: energy landscapes of pyrimidine dimers in gas phase and water.

The potential energy surfaces of stacked base pairs consisting of cytosine (C), thymine (T), uracil (U) and the mutagenic thymine analogue 5-bromouracil (BrU) have been searched to obtain all possible minima. Minima and transition states were optimised at the counterpoise-corrected M06-2X/6-31+G(d) level, both in the gas phase and in water, modelled by the polarizable continuum model. The stacked dimers studied are BrU/BrU, C/BrU, C/C, C/T, C/U, T/BrU and T/U. Both face-to-back and face-to-face structures were considered. Free energies were calculated at 298.15 K. Together with U/U, T/T and BrU/U results from previous work, these results complete the family consisting of every stacked dimer combination consisting of C, T, U and BrU. The results were used to assess the hypothesis suggested in the literature that BrU stacks stronger than T, which could stabilise the mispair formed by BrU and guanine. In the gas phase, structures of C/BrU, T/BrU and U/BrU with greater zero-point-corrected binding energies than C/T, T/T and U/T, respectively, were found, with differences in favour of BrU of 3.1 kcal mol(-1), 1.7 kcal mol(-1) and 0.5 kcal mol(-1), respectively. However, the structure of these dimers differed considerably from anything encountered in DNA. When only the dimers with the most "DNA-like" twist (±36°) were considered, C/BrU and T/BrU were still more strongly bound than C/T and T/T, by 0.5 kcal mol(-1) and 1.7 kcal mol(-1), respectively. However, when enthalpic and/or solvent contributions were taken into account, the stacking advantage of BrU was reversed in the gas phase and mostly nullified in water. Enhanced stacking therefore does not seem a plausible mechanism for the considerably greater ability of BrU-G mispairs over T-G mispairs to escape enzymatic repair.

Charge density studies of nucleobase analogues - the case of DAP and isocytosine

Nucleobases belong to purine and pyrimidine family and constitute a biologically crucial group of compounds thank to their relation to nucleic acids. Specific interactions between these moieties are responsible for maintaining a proper structure of DNA, namely: hydrogen bonding and π-π stacking interactions (between aromatic ring fragments). Furthermore, many modifications of natural nucleobases serve as drugs, but some could be extremely harmful. In view of the above, investigating the properties of analogues of nucleobases may contribute to our knowledge about nucleic acid properties in general and give an opportunity to find novel ligands binding to DNA, what is essential for drug design. Within this project two modified nucleobases were examined: 2,6-diaminopurine (DAP) and isocytosine (iC). DAP is a derivative of the adenine and iC is an isomer of cytosine. These compounds do not appear naturally in nucleic acids, however, can be used to compare Watson-Crick pairing in DNA and pairing of alternative bases. High resolution X-ray diffraction experiments were carried out to obtain appropriate data for charge density analysis. A comprehensive study of crystal packing and energetic features of the analysed systems was conducted. The nature of intermolecular interactions, structural motifs and crystal packing was analysed via Hirshfeld surface analysis [1], charge density distribution examination, QTAIM (Quantum Theory of Atoms in Molecules) [2] and theoretical calculations (gas phase dimers and periodic). Implications of the observed interactions for biological systems are discussed. This study was supported by the Polish Ministry of Science and Higher Education within the Diamond Grant No DI 2011012441.

Cooperativity of Halogen, Chalcogen, and Pnictogen Bonds in Infinite Molecular Chains by Electronic Structure Theory

Halogen bonds (XBs) are intriguing noncovalent interactions that are frequently being exploited for crystal engineering. Recently, similar bonding mechanisms have been proposed for adjacent main-group elements, and noncovalent "chalcogen bonds" and "pnictogen bonds" have been identified in crystal structures. A fundamental question, largely unresolved thus far, is how XBs and related contacts interact with each other in crystals; similar to hydrogen bonding, one might expect "cooperativity" (bonds amplifying each other), but evidence has been sparse. Here, we explore the crucial step from gas-phase oligomers to truly infinite chains by means of quantum chemical computations. A periodic density functional theory (DFT) framework allows us to address polymeric chains of molecules avoiding the dreaded "cluster effects" as well as the arbitrariness of defining a "large enough" cluster. We focus on three types of molecular chains that we cut from crystal structures; furthermore, we explore reasonable substitutional variants in silico. We find evidence of cooperativity in chains of halogen cyanides and also in similar chalcogen- and pnictogen-bonded systems; the bonds, in the most extreme cases, are amplified through cooperative effects by 79% (I···N), 90% (Te···N), and 103% (Sb···N). Two experimentally known organic crystals, albeit with similar atomic connectivity and XB characteristics, show signs of cooperativity in one case but not in another. Finally, no cooperativity is observed in alternating halogen/acetone and halogen/1,4-dioxane chains; in fact, these XBs weaken each other by up to 26% compared to the respective gas-phase dimers.

Quantum Mechanical Calculation of Noncovalent Interactions: A Large-Scale Evaluation of PMx, DFT, and SAPT Approaches.

Quantum mechanical (QM) calculations of noncovalent interactions are uniquely useful as tools to test and improve molecular mechanics force fields and to model the forces involved in biomolecular binding and folding. Because the more computationally tractable QM methods necessarily include approximations, which risk degrading accuracy, it is essential to evaluate such methods by comparison with high-level reference calculations. Here, we use the extensive Benchmark Energy and Geometry Database (BEGDB) of CCSD(T)/CBS reference results to evaluate the accuracy and speed of widely used QM methods for over 1200 chemically varied gas-phase dimers. In particular, we study the semiempirical PM6 and PM7 methods; density functional theory (DFT) approaches B3LYP, B97-D, M062X, and ωB97X-D; and symmetry-adapted perturbation theory (SAPT) approach. For the PM6 and DFT methods, we also examine the effects of post hoc corrections for hydrogen bonding (PM6-DH+, PM6-DH2), halogen atoms (PM6-DH2X), and dispersion (DFT-D3 with zero and Becke–Johnson damping). Several orders of the SAPT expansion are also compared, ranging from SAPT0 up to SAPT2+3, where computationally feasible. We find that all DFT methods with dispersion corrections, as well as SAPT at orders above SAPT2, consistently provide dimer interaction energies within 1.0 kcal/mol RMSE across all systems. We also show that a linear scaling of the perturbative energy terms provided by the fast SAPT0 method yields similar high accuracy, at particularly low computational cost. The energies of all the dimer systems from the various QM approaches are included in the Supporting Information, as are the full SAPT2+(3) energy decomposition for a subset of over 1000 systems. The latter can be used to guide the parametrization of molecular mechanics force fields on a term-by-term basis.