Dispersion-corrected Density Functional Theory Methods Research Articles

Surface Engineering of the Mechanical Properties of Molecular Crystals via an Atomistic Model for Computing the Facet Stress Response of Solids.

Dynamic molecular crystals are an emerging class of crystalline materials that can respond to mechanical stress by dissipating internal strain in a number of ways. Given the serendipitous nature of the discovery of such crystals, progress in the field requires advances in computational methods for the accurate and high-throughput computation of the nanomechanical properties of crystals on specific facets which are exposed to mechanical stress. Here, we develop and apply a new atomistic model for computing the surface elastic moduli of crystals on any set of facets of interest using dispersion-corrected density functional theory (DFT-D) methods. The model was benchmarked against a total of 24 reported nanoindentation measurements from a diverse set of molecular crystals and was found to be generally reliable. Using only the experimental crystal structure of the dietary supplement, L-aspartic acid, the model was subsequently applied under blind test conditions, to correctly predict the growth morphology, facet and nanomechanical properties of L-aspartic acid to within the accuracy of the measured elastic stiffness of the crystal, 24.53±0.56 GPa. This work paves the way for the computational design and experimental realization of other functional molecular crystals with tailor-made mechanical properties.

An Assessment of Dispersion-Corrected DFT Methods for Modeling Nonbonded Interactions in Protein Kinase Inhibitor Complexes.

Accurate modeling of nonbonded interactions between protein kinases and their small molecule inhibitors is essential for structure-based drug design. Quantum chemical methods such as density functional theory (DFT) hold significant promise for quantifying the strengths of these key protein-ligand interactions. However, the accuracy of DFT methods can vary substantially depending on the choice of exchange-correlation functionals and associated basis sets. In this study, a comprehensive benchmarking of nine widely used DFT methods was carried out to identify an optimal approach for quantitative modeling of nonbonded interactions, balancing both accuracy and computational efficiency. From a database of 2139 kinase-inhibitor crystal structures, a diverse library of 49 nonbonded interaction motifs was extracted, encompassing CH-π, π-π stacking, cation-π, hydrogen bonding, and salt bridge interactions. The strengths of nonbonded interaction energies for all 49 motifs were calculated at the advanced CCSD(T)/CBS level of theory, which serve as references for a systematic benchmarking of BLYP, TPSS, B97, ωB97X, B3LYP, M062X, PW6B95, B2PLYP, and PWPB95 functionals with D3BJ dispersion correction alongside def2-SVP, def2-TZVP, and def2-QZVP basis sets. The RI, RIJK, and RIJCOSX approximations were used for selected functionals. It was found that the B3LYP/def2-TZVP and RIJK RI-B2PLYP/def2-QZVP methods delivered the best combination of accuracy and computational efficiency, making them well-suited for efficient modeling of nonbonded interactions responsible for molecular recognition of protein kinase inhibitors in their targets.

Separation of High-Purity C2H2 from Binary C2H2/CO2 Using Robust Al-Based MOFs Comprising Nitrogen-Containing Heterocyclic Dicarboxylate.

In this study, three nitrogen-containing aluminum-based metal-organic frameworks (Al-MOFs), namely, CAU-10pydc, MOF-303, and KMF-1, were investigated for the efficient separation of a C2H2/CO2 gas mixture. Among these three Al-MOFs, KMF-1 demonstrated the highest selectivity for C2H2/CO2 separation (6.31), primarily owing to its superior C2H2 uptake (7.90 mmol g-1) and lower CO2 uptake (2.82 mmol g-1) compared to that of the other two Al-MOFs. Dynamic breakthrough experiments, using an equimolar binary C2H2/CO2 gas mixture, demonstrated that KMF-1 achieved the highest separation performance. It yielded 3.42 mmol g-1 of high-purity C2H2 (>99.95%) through a straightforward desorption process under He purging at 298 K and 1 bar. To gain insights into the distinctive characteristics of the pore surfaces of structurally similar CAU-10pydc and KMF-1, we conducted computational simulations using canonical Monte Carlo and dispersion-corrected density functional theory methods. These simulations revealed that the secondary amine (C2N-H) groups in KMF-1 played a more significant role in differentiating between C2H2 and CO2 compared to that of the N atoms in CAU-10pydc and MOF-303. Consequently, KMF-1 emerged as a promising adsorbent for the separation of high-purity C2H2 from binary C2H2/CO2 gas mixtures.

Relative energies of increasingly large [n]helicenes by means of high-level quantum chemical methods

We investigate the relative stability of increasingly large helicenes at the CCSD(T) level via the high-level G4(MP2) thermochemical protocol. The relative energies of [n]helicenes (n = 4–9) are obtained via the following reaction: [n]helicene + benzene → [n + 1]helicene + ethene. This reaction conserves the number of sp2-hybridized carbons, the number of aromatic rings, and the helical structures on the two sides of the reaction. We show that the reaction energy converges to an asymptotic value of ΔH298 = + 22.4 kJ/mol for increasingly large helicenes. For comparison, for [n]acenes, the same reaction converges to a much higher asymptotic reaction enthalpy of ΔH298 = + 56.8 kJ/mol. This difference between the two asymptotic reaction enthalpies sheds light on the relative thermodynamic stability of increasingly large helicenes. We proceed to use the G4(MP2) reaction energies to evaluate the performance of dispersion-corrected density functional theory (DFT) and semiempirical molecular orbital (SMO) methods for the relative energies of [n]helicenes. Nearly all DFT methods perform poorly with root-mean-square deviations (RMSDs) above 10 kJ/mol. The best-performing DFT method, BLYP-D4, attains an RMSD = 5.2 kJ/mol. Surprisingly, the advanced SMO methods, XTB and PM7, outperform the DFT methods and result in RMSDs of 3.0 and 3.1 kJ/mol, respectively.

Dispersion-Corrected DFT-D4 Study of the Adsorption of Halobenzenes and 1,3,5-Trihalobenzenes on the Cu(111) Surface─Effect of Sigma Hole Properties.

Halogen bonds, characterized by directionality, tunability, hydrophobicity, and variable sizes, are ideal noncovalent interactions to design and control the formation of self-assembled nanostructures. The specific self-assembly cases formed by the halogen-bonding interaction have been well studied by scanning tunneling microscopy (STM) experiments and density functional theory (DFT) calculations. However, there is a lack of systematic theoretical adsorption studies on halogenated molecules. In this work, the adsorption of halobenzenes and 1,3,5-trihalobenzenes on the Cu(111) surface was examined by dispersion-corrected DFT methods. The adsorption geometries, noncovalent molecule-surface interactions, electronic densities, and electrostatic potential maps were examined for their most stable adsorption sites using the DFT-D4 method. Our calculations revealed that the iodo compounds favor a different adsorption geometry from aryl chlorides and bromides. Down the halogen group (Cl to I), the adsorption energy increases and the distance between the halogen atom and Cu surface decreases, which indicates stronger molecule-surface interactions. This is supported by the changes in the density of states upon adsorption. Noncovalent interaction analysis was also employed to further understand the nature and relative strength of the molecule-surface interactions. Electrostatic potential maps revealed that the positive character of the halogen sigma hole becomes stronger upon adsorption. Thus, surface adsorption of the halogenated molecule will enhance the formation of intermolecular halogen bonds. The present theoretical findings are expected to contribute toward a more comprehensive understanding of halogen bonding on the Cu(111) surface.

Energetics and Ionic–Electronic and Geometric Variabilities of Hydroxylammonium-Based Salts

In the present work, we study the formation energy of energetic ionic salts (EISs), as well as the volumetric and electric variabilities of ions involved in EISs, by employing 25 hydroxylammonium cations (HA+) in 22 salts as examples. We identify the viability of a dispersion-corrected density functional theory method, PBE-D3(BJ), to describe the lattice parameters, with a mean relative deviation of 1.26% and a maximal relative deviation of 2.5%. Thereby, the ionization energy, formation energy, and lattice energy are predicted. The variability of volume (VHA+) is confirmed in different HA+-based salts, as well as between two HA+ of the same lattice with Z′ > 1. The largest difference of VHA+ among the 25 HA+ reaches ∼9%. This variability of VHA+ is originated from the difference in crystal field effects, or intermolecular interactions. That is, the stronger intermolecular hydrogen bond tends to exhibit a stronger drag and pull effect on HA+ and leads to a larger VHA+. In comparison, it exhibits a more significant variability of electricity, as the maximal total Mulliken charge of HA+ (QHA+) is >1.67 times the minimal one. Moreover, the observed QHA+ varying from 0.164 to 0.438 e is much less than the apparent charge of 1 e, suggesting the highly insufficient charge of HA+ in EISs. This means that the ionic bonding does not necessarily govern the intermolecular interactions in common EISs. Besides, an electrostatic potential (ESP) minimum-oxygen balance (OB) correlation is found in the anions countering HA+, as the more negative OB tends to cause a more negative ESP minimum. All of these findings are expected to richen the insight into the nature of EISs as a special group of EMs.

Adsorption of imidazolium-based ionic liquids on the Fe(1 0 0) surface for corrosion inhibition: Physisorption or chemisorption?

The use of imidazolium-based ionic liquids (ILs) as corrosion inhibitors for iron was studied using both first-principles based density functional theory (DFT) calculations and ab initio molecular dynamics (AIMD), to understand their adsorption structure, stability, and mechanism. A total of 36 ionic liquids (ILs) were selected, with various anion type (Cl−, Br−, I−, N(CN)2−, BF4− and PF6−) and alkyl chain length (Cn, n = 0, 1, 2, 4 and 6). Our calculations revealed that the ILs exhibit strong adsorption on the metal surface and is classified as chemisorption under various different criteria. AIMD simulations including explicit solvation effects verified that these adsorption configurations calculated under vacuum are representative of the adsorption process in an aqueous environment. Furthermore, we showed that the basis of this chemisorption interaction is through net electron donation from the iron slab to the imidazolium ring. Employing dispersion corrected DFT methods (DFT-D3), we demonstrated that the alkyl chain length of the cation greatly influences adsorption energy. Finally, we showed that DFT calculations model the adsorption process much more accurately compared to classical molecular dynamics calculations. The results from this computational study agree with past experimental findings and demonstrate that DFT calculations can be used to provide insight into the nature of the adsorption process of the green and sustainable ILs involved in corrosion inhibition.

Verification of the Accuracy and Efficiency of Dispersion-Corrected Density Functional Theory Methods to Describe the Lattice Structure and Energy of Energetic Cocrystals

Verification of the Accuracy and Efficiency of Dispersion-Corrected Density Functional Theory Methods to Describe the Lattice Structure and Energy of Energetic Cocrystals

Synthesis, X-ray crystallography, molecular electronic property investigation, and leukopoiesis activity of novel 4,6-dimethyl-1,6-dihydropyridin-2-amino nitrate hybrid material

Herein, a new hybrid organic-inorganic material: 4,6-dimethyl-1,6-dihydropyridin-2-amino nitrate (I) has been synthesized and characterized by X-ray diffraction technique and Fourier transform infrared (FT-IR) spectroscopy. The structural, electronic and topological properties were investigated by a theoretical approach along with a validation of vibrational properties using the dispersion-corrected density functional theory (DFT-D3) method (PWPB95 D3(BJ)) along with the meta-generalized gradient approximation (Meta-GGA) functional of the Minnesota family (M06–2x). All computations were conducted with the 6–311++G(2df,2pd) and def2-TZVP basis set. A visual study of weak interactions was achieved via Bader's Quantum theory of atoms in molecules (QTAIM), non-covalent interaction (NCI) using the promolecular electron density approach, Electron localization function and molecular electrostatic potential. Natural orbital analysis and charge delocalization were equally considered to comprehend and appraise the various intermolecular stabilization mechanisms in the studied system. Molecular electronic properties (quantum descriptors) were also investigated to assess the reactive nature and stability index of the synthesized structure. Due to the ionic nature and structural similarity of the studied compound with methyluracil, molecular docking investigations of the Leukopoiesis stimulating activity of (I) were assessed and compared with a series of Krebs ’regulating enzymes. These studies divulged that the synthesized compound has the potential to stimulate the synthesis of nucleic acids, proteins, cell division, and leukopoiesis.

Model Compounds for Intermediates and Transition States in Sonogashira and Negishi Coupling:d8–d10Bonds in Large Heterobimetallic Complexes Are Weaker than Computational Chemistry Predicts

We report an experimental study, with accompanying DFT calculations, on a series of heterobimetallic complexes with Pd(II) and Cu(I), Ag(I), or Au(I). The isolable pincer complexes are models for the intermediates and transition state for the transmetalation step in Sonogashira and Negishi coupling reactions, among which, according to the DFT calculations, only the transition state has the two metal centers within bonding distance. Furthermore, we report a substituted version of an analogous heterobimetallic complex in which a competing dissociation sets an upper-bound on the strength of the d8-d10 metal-metal bond. Analysis of the structures in the solid state and in solution, and the competitive dissociation experiment in the gas phase, indicate that the dispersion-corrected DFT method used in the study appears to overestimate the strength of the metal-metal interaction, thus distorting the shape of the computed potential energy surface systematically for transmetalation.

Ambiguous structure determination from powder data: four different structural models of 4,11-di-fluoro-quinacridone with similar X-ray powder patterns, fit to the PDF, SSNMR and DFT-D.

Four different structural models, which all fit the same X-ray powder pattern, were obtained in the structure determination of 4,11-di-fluoro-quinacridone (C20H10N2O2F2) from unindexed X-ray powder data by a global fit. The models differ in their lattice parameters, space groups, Z, Z', molecular packing and hydrogen bond patterns. The molecules form a criss-cross pattern in models A and B, a layer structure built from chains in model C and a criss-cross arrangement of dimers in model D. Nevertheless, all models give a good Rietveld fit to the experimental powder pattern with acceptable R-values. All molecular geometries are reliable, except for model D, which is slightly distorted. All structures are crystallochemically plausible, concerning density, hydrogen bonds, intermolecular distances etc. All models passed the checkCIF test without major problems; only in model A a missed symmetry was detected. All structures could have probably been published, although 3 of the 4 structures were wrong. The investigation, which of the four structures is actually the correct one, was challenging. Six methods were used: (1) Rietveld refinements, (2) fit of the crystal structures to the pair distribution function (PDF) including the refinement of lattice parameters and atomic coordinates, (3) evaluation of the colour, (4) lattice-energy minimizations with force fields, (5) lattice-energy minimizations by two dispersion-corrected density functional theory methods, and (6) multinuclear CPMAS solid-state NMR spectroscopy (1H, 13C, 19F) including the comparison of calculated and experimental chemical shifts. All in all, model B (perhaps with some disorder) can probably be considered to be the correct one. This work shows that a structure determination from limited-quality powder data may result in totally different structural models, which all may be correct or wrong, even if they are chemically sensible and give a good Rietveld refinement. Additionally, the work is an excellent example that the refinement of an organic crystal structure can be successfully performed by a fit to the PDF, and the combination of computed and experimental solid-state NMR chemical shifts can provide further information for the selection of the most reliable structure among several possibilities.

CB[7]- and CB[8]-Based [2]-(Pseudo)rotaxanes with Triphenylphosphonium-Capped Threads: Serendipitous Discovery of a New High-Affinity Binding Motif.

The synthesis of new triphenylphosphonium-capped cucurbit[7]uril (CB[7])- and cucurbit[8]uril (CB[8])-based [2]rotaxanes was achieved by a simultaneous threading-capping strategy. While the use of CB[7] produced the designed [2]rotaxane, attempts to obtain the CB[8] analogue were unsuccessful due to the unexpected strong interaction found between the host and the phosphonium caps leading to pseudo-heteroternary host–guest complexes. This unusual binding motif has been extensively studied experimentally, with results in good agreement with those obtained by dispersion-corrected DFT methods.

Adsorption of Transition-Metal Clusters on Graphene and N-Doped Graphene: A DFT Study.

Using the dispersion-corrected density functional theory (DFT-D3) method, we systematically studied the adsorption of 15 kinds of transition-metal (TM) clusters on pristine graphene (Gr) and N-doped graphene (N-Gr). It has been found that TMn (n = 1-4) clusters adsorbed on the N-Gr surface are much stronger than those on the pristine Gr surface, while 3d series clusters present similar geometries on Gr and N-Gr surfaces. The most preferred sites of TMs migrate from hollow to bridge to the top site on the Gr surface along the d series in the periodic table, while the preferred sites of TMs migrate in a much more complex manner on the N-Gr surface. It has also been found that charge transfer decreases along the d series for adsorbed clusters on both surfaces, but adsorbed clusters present less charge transfer on the N-Gr surface than on the Gr surface. What is more interesting is that some TM (Tc, Ru, and Re) clusters change the growth mechanism from the three-dimensional (3D) growth mode on the Gr surface to the two-dimensional (2D) growth mode on the N-Gr surface. At last, it has been found that adsorbed clusters are more dispersed on the N-Gr surface than on the pristine Gr surface due to growth and average aggregation energies.

Understanding the effect of transition metals and vacancy boron nitride catalysts on activity and selectivity for CO2 reduction reaction to valuable products: A DFT-D3 study

Single-atom catalysts have recently emerged as a promising approach for catalyzing the electrochemical CO2 reduction reaction (CRR). Transition metal (TM) atom doping to 2-dimensional layer material has been studied for CRR, but compared to studies on TM doped single vacancy (TM-SV) sites, those on double vacancies (TM-DV) sites are minor. In this research, we investigated the doping of 26 (3d-, 4d-, and 5d-groups) TM atoms to the DV of boron nitride nanosheets (BN) using the dispersion-corrected density functional theory method for the complete CRR mechanism. We analyzed the limiting potential of the reactions of different TM-DVBN using the integrated crystal orbital Hamiltonian partition (ICOHP) of TM–O binding, universal descriptor, charge, and the number of valence electrons. We found the volcano plot model which suggests that a moderate OH binding energy of around −0.50 eV, the universal descriptor value around 9.40, and the ICOHP descriptor around −0.20 will provide the lowest limiting potential for CRR. From these studies, we find Ni-DVBN is the most reactive and can produce CH3OH at −0.48 V. This is much better than Ni-SVBN, which requires −1.0 V to produce HCOOH also lower than Fe-SVBN (−0.52 V), which was the best catalyst in the previous study of TM-SVBN. This shows that Ni doping to DVBN is more effective for CRR compared to doping to SVBN.

A DFT analysis of electronic, reactivity, and NLO responses of a reactive orange dye: the role of Hartree-Fock exchange corrections.

An experimental and theoretical study based on DFT/TD-DFT approximations is presented to understand the nature of electronic excitations, reactivity, and nonlinear optical (NLO) properties of reactive orange 16 dye (RO16), an azo chromophore widely used in textile and pharmacological industries. The results show that the solvent has a considerable influence on the electronic properties of the material. According to experimental results, the absorption spectrum is formed by four intense transitions, which have been identified as [Formula: see text] states using TD-DFT calculations. However, the TD-DFT results reveal a weak [Formula: see text] in the low-lying spectral region. Continuum models of solvation indicate that these states suffer from bathochromic (ca. 15 nm) and hypsochromic shifts (ca. 4 nm), respectively. However, the expected blue shift for the absorption [Formula: see text] is only described using long-range or dispersion-corrected DFT methods. RO16 is classified as a strong electrophilic system, with electrophilicity ω > 1.5 eV. Concerning the nucleophilicity parameter (N), from vacuum to solvent, the environment is active and changes the nucleophilic status from strong to moderate nucleophile (2.0 ≤ N ≤ 3.0 eV). The results also suggest that all electrical constants are strongly dependent on long-range and Hartree-Fock exchange contributions, and the absence of these interactions gives results far from reality. In particular, the results for the NLO response show that the chromophore presents a potential application in this field with a low refractive index and first hyperpolarizability ca. 214 times bigger than the value usually reported for urea (β = 0.34 × 10- 30 esu), which is a standard NLO material. Concerning the solvent effects, the results indicate that the polarizability increases [Formula: see text] esu from gas to solvent while the first hyperpolarizability is calculated as [Formula: see text] esu, ca. 180%, regarding the vacuum. The results suggest RO16 is a potential compound in NLO applications. Graphical Abstract The frontier molecular orbitals, and the inverse relation between the energy-gap (Egap) and the first hyperpolarizability (β).

Toward accurate ab initio modeling of siliceous zeolite structures.

Structures of purely siliceous materials in the International Zeolite Association database were investigated with four different theoretical methods ranging from the empirical approaches, such as the distance least squares and force fields to the computationally demanding dispersion-corrected density functional theory method employing the generalized gradient approximation-type functional. The structural characteristics were first evaluated for dense silica polymorphs, for which reliable low-temperature experiments are available. Due to the significant errors in experimentally determined atomic positions of siliceous zeolites, lattice parameters and the cell volume were proposed as reliable descriptors for the structural assessment of zeolite frameworks. In this regard, the most consistently performing (systematically underestimating/overestimating) methods are the Sanders-Leslie-Catlow (SLC) force field and the PBEsol density functional. The best overall agreement with the experiment is observed for PBEsol-D2. However, it is a result of fortuitous error cancellations rather than improved description upon adding dispersion correction. We proposed two approaches to estimate accurate cell volumes of siliceous materials from theoretical data: (i) using the SLC and PBEsol volumes as lower and upper bounds and (ii) using a structural response to the dispersion correction along with the SLC compressibility as an additional criterion.

Strength and Nature of Host-Guest Interactions in Metal-Organic Frameworks from a Quantum-Chemical Perspective.

Metal‐organic frameworks (MOFs) offer a convenient means for capturing, transporting, and releasing small molecules. Their rational design requires an in‐depth understanding of the underlying non‐covalent host‐guest interactions, and the ability to easily and rapidly pre‐screen candidate architectures in silico. In this work, we devised a recipe for computing the strength and analysing the nature of the host‐guest interactions in MOFs. By assessing a range of density functional theory methods across periodic and finite supramolecular cluster scale we find that appropriately constructed clusters readily reproduce the key interactions occurring in periodic models at a fraction of the computational cost. Host‐guest interaction energies can be reliably computed with dispersion‐corrected density functional theory methods; however, decoding their precise nature demands insights from energy decomposition schemes and quantum‐chemical tools for bonding analysis such as the quantum theory of atoms in molecules, the non‐covalent interactions index or the density overlap regions indicator.

Rare Tautomers of Artificially Expanded Genetic Letters and their Effects on the Base Pair Stabilities.

In order to expand the existing genetic letters, it is necessary to design robust nucleotides that can function naturally in living cells. Therefore, it is desirable to examine the roles of recently-proposed second-generation artificially genetic letters in producing stable duplex DNA. Herein, a reliable dispersion-corrected density functional theory method is used to shed light on the electronic structures and properties of different rare tautomers of proposed expanded genetic letters and their effects on the base pair stabilities in the duplex DNA. It is found that the rare tautomers are not only stable in the aqueous medium but can also pair with natural bases to produce stable mispairs. Except for J and V, all of the artificial genetic letters are found to produce mispairs that are about 1-7 kcal mol-1 more stable than their complementary counterparts. They are also appreciably more stable than the naturally occurring G : C, A : T, and G : T pairs. Mainly attractive electrostatic interactions and polarity of the monomers are responsible for the higher base pair stabilities.

Modulation of graphene and graphdiyne by metaln (n = 1–5) adsorption and nucleation and the effect on hydrogen evolution reaction

Comprehending the interaction of metal clusters with two-dimensional (2D) carbon materials at the atomic level is important for the rational design of relative materials for various applications. The geometrical and electronic modulation of graphene and graphdiyne (GDY) by the adsorption and nucleation of Cun, Irn, and Pdn (n = 1–5) and the effect on hydrogen evolution reaction (HER) were studied employing dispersion-corrected density functional theory methods. The bonding strength between the metal Mn (n = 1–5) clusters and the considered 2D materials generally followed the order of Irn-substrate > Pdn-substrate > Cun-substrate. The modified electronic properties induced by the metal decoration affected the H adsorption. According to the Sabatier’s principle, the Mn@graphene present better HER catalytic properties than the pristine graphene, while the Mn@GDY depends. Based on the calculated ΔG0(H) and H diffusion barrier, H can easily diffuse from the C site of graphene to the metal site and show better HER activities. The reverse H diffusion from the metal site to the carbon site of GDY for GDY supported Pd1, Pd5, and Ir5 could happen at room temperature, thereby improving the HER activity at pH = 0. A series of linear relationships are found, revealing the possible structure–activity relations.

Enhancing the Accuracy of Ab Initio Molecular Dynamics by Fine Tuning of Effective Two-Body Interactions: Acetonitrile as a Test Case.

Grimme's dispersion-corrected density functional theory (DFT-D) methods have emerged among the most practical approaches to perform accurate quantum mechanical calculations on molecular systems ranging from small clusters to microscopic and mesoscopic samples, i.e., including hundreds or thousands of molecules. Moreover, DFT-D functionals can be easily integrated into popular ab initio molecular dynamics (MD) software packages to carry out first-principles condensed-phase simulations at an affordable computational cost. Here, starting from the well-established D3 version of the dispersion-correction term, we present a simple protocol to improve the accurate description of the intermolecular interactions of molecular clusters of growing size, considering acetonitrile as a test case. Optimization of the interaction energy was performed with reference to diffusion quantum Monte Carlo calculations, successfully reaching the same inherent accuracy of the latter (statistical error of ∼0.1 kcal/mol per molecule). The refined DFT-D3 model was then used to perform ab initio MD simulations of liquid acetonitrile, again showing significant improvements toward available experimental data with respect to the default correction.