Gauge-including Atomic Orbitals Research Articles

Multiconfigurational short-range density functional theory for nuclear magnetic resonance shielding constants with gauge-including atomic orbitals.

In this paper, we present the theory and implementation of nuclear magnetic resonance shielding constants with gauge-including atomic orbitals for the hybrid multiconfigurational short-range density functional theory model. As a special case, this implementation also includes Hartree-Fock srDFT (HF-srDFT). Choosing a complete-active space (CAS) wave function as the multiconfigurational parameterization of the wave function, we investigate how well CAS-srDFT reproduces experimental trends of nuclear shielding constants compared to DFT and complete active space self-consistent field (CASSCF). Calculations on the nucleobases adenine and thymine show that CAS-srDFT performs on average the best of the tested methods, much better than CASSCF but only marginally better than HF-srDFT. The performance, compared to regular DFT, is similar when functionals containing exact exchange are used. We generally find that the inclusion of exact exchange is important for an accurate description of the shielding constants. In cases where no exact exchange is included, we observe that the HF- and CAS-srDFT often outperform regular DFT. For calculations on transition metal nuclei in organometallic compounds with significant static correlation, the CAS-srDFT method again outperforms CASSCF compared to experimental shielding constants, and the change from HF-srDFT is substantial. In conclusion, the static correlation posed by the metal complexes seems to be captured by CAS-srDFT, which is promising since this type of correlation is not well described by regular DFT.

Two new p-methoxyphenyl-type derivatives from a saline-lake derived Streptomyces sp. XZB32

Two new p-methoxyphenyl-type derivatives cytchloramol (1) and cytoxazinanone (2), along with six known compounds (3-8) were identified from the chemical investigations of a saline lake actinomycete, Streptomyces sp. XZB32. The structures of the new compounds were elucidated by extensive NMR spectroscopic analysis, HRESIMS data, GIAO (gauge-including atomic orbitals) NMR, specific optical rotation (SOR) and electronic circular dichroism (ECD) calculations. Cytotoxicity evaluation of the two new compounds showed that compound 1 exhibited significant activity against HCT-116 and MDA-MB-231 human cancer cell line with IC50 values of 2.7 ± 0.07 µM and 1.54 ± 0.14 µM, respectively.

Computation of NMR shieldings at the CASSCF level using gauge-including atomic orbitals and Cholesky decomposition.

We present an implementation of coupled-perturbed complete active space self-consistent field (CP-CASSCF) theory for the computation of nuclear magnetic resonance chemical shifts using gauge-including atomic orbitals and Cholesky decomposed two-electron integrals. The CP-CASSCF equations are solved using a direct algorithm where the magnetic Hessian matrix-vector product is expressed in terms of one-index transformed quantities. Numerical tests on systems with up to about 1300 basis functions provide information regarding both the computational efficiency and limitations of our implementation.

Cholesky decomposition of two-electron integrals in quantum-chemical calculations with perturbative or finite magnetic fields using gauge-including atomic orbitals

A rigorous analysis is carried out concerning the use of Cholesky decomposition (CD) of two-electron integrals in the case of quantum-chemical calculations with finite or perturbative magnetic fields and gauge-including atomic orbitals. We investigate in particular how permutational symmetry can be accounted for in such calculations and how this symmetry can be exploited to reduce the computational requirements. A modified CD procedure is suggested for the finite-field case that roughly halves the memory demands for the storage of the Cholesky vectors. The resulting symmetry of the Cholesky vectors also enables savings in the computational costs. For the derivative two-electron integrals in case of a perturbative magnetic field we derive CD expressions by means of a first-order Taylor expansion of the corresponding finite magnetic-field formulas with the field-free case as reference point. The perturbed Cholesky vectors are shown to be antisymmetric (as already proposed by Burger et al. [ J. Chem. Phys. 155, 074105 (2021)]) and the corresponding expressions enable significant savings in the required integral evaluations (by a factor of about four) as well as in the actual construction of the Cholesky vectors (by means of a two-step procedure similar to the one presented by Folkestad et al. [J. Chem. Phys. 150, 194112 (2019)] and Zhang et al. [J. Phys. Chem. A 125, 4258–4265 (2021)]). Numerical examples with cases involving several hundred basis functions verify our suggestions concerning CD in case of finite and perturbative magnetic fields.

17O NMR and DFT study of hydrogen bonding: Proton sharing and incipient transfer

17O NMR spectra of pyridine N-oxide (PyO) complexes with the acids – acetic (AA), cyanoacetic (CyA), propiolic (PA), trichloroacetic (TCA), trifluoroacetic (TFA), hydrochloric (HCl) and methanesulfonic (MSA) – as well as some related molecules with intramolecular H-bonds (4-substituted picolinic acid N-oxides) were studied in an acetonitrile (ACN) solution. In order to evaluate the effect of proton positioning along the O–H…O bond on the measured chemical shifts the full geometry optimization was carried out, and 17O magnetic shielding tensors were calculated using density functional theory (DFT). The modified hybrid functional PBE1PBE with the 6-311++G** basis set and the gauge-including atomic orbital (GIAO) approach were applied. The solvent effect was taken into account by a polarized continuum model using the integral equation formalism (IEFPCM). Two stable structures were deduced for the PyO complexes with TCA and TFA that correspond to the H-bonds with and without proton transfer (PT). Two minima on the potential surface were separated by ca 0.2 Å. The experimental 17O NMR spectra have shown that the PyO-TCA complex in ACN can be considered as H-bonding with incipient PT, whereas it is known from neutron diffraction that in its crystalline state PT occurs. The proton location in PyO-TFA due to the thermally induced proton sharing was found at the middle point. The 17O NMR data for the acids with an intramolecular H-bond (nitroPANO, PANO and methoxyPANO) deviate from the general trend. The factors that can cause it, such as the substitution effect, persistence of nano-crystallites in a solution due to a low solubility, etc., have been discussed.

Novel geranylhydroquinone derived meroterpenoids from the fungus Clitocybe clavipes and their cytotoxic activity

Three novel geranylhydroquinone derived meroterpenoids, named clavilactones J and K (1–2) and clavipol C (3), were isolated from the basidiomycete Clitocybe clavipes. Their structures were unambiguously identified by extensive spectroscopic data analysis, and the electronic circular dichroism (ECD) calculation, Gauge-Including Atomic Orbitals (GIAO) NMR calculations and Mo2(OAc)4-induced electronic circular dichroism experiments were used to establish their absolute configurations. Compound 1, with two epoxy groups located at the 10-membered carbocycle, is uncommon in the reported meroterpenoids from C. clavipes. All the obtained compounds (1–3) were tested for their cytotoxic activity against human tumor cell line HGC-27 by using the MTT assay. All the compounds exhibited moderate cytotoxic activities against HGC-27 cell with IC50 values ranging from 33.5 to 56.6 μM.

Spherical Aromaticity of Tetrahedral Pnictogens Through Off-Nucleus Isotropic Magnetic Shielding.

This work revealed the spherical aromaticity of some inorganic E4 cages and their protonated E4 H+ ions (E=N, P, As, Sb, and Bi). For this purpose, we employed several evaluations like (0D-1D) nucleus independent chemical shift (NICS), multidimensional (2D-3D) off-nucleus isotropic shielding σiso (r), and natural bond orbital (NBO) analysis. The magnetic calculations involved gauge-including atomic orbitals (GIAO) with two density functionals B3LYP and WB97XD, and basis sets of Jorge-ATZP, 6-311+G(d,p), and Lanl2DZp. The Jorge-ATZP basis set showed the best consistency. Our findings disclosed non-classical aromatic characters in the above molecules, which decreased from N to Bi cages. Also, the results showed more aromaticity in E4 than E4 H+ . The NBO analysis attributed the aromaticity in the above molecules to the residual density of the overlapping σ-bonding orbitals. So, the aromaticity in these molecules is unlike the classical aromaticity that is associated with electron delocalization. Scanning 1D σiso (r) variation along E-E bonds indicated a lowering in the shielding trend from N to Bi cages. The 3D results showed a similar decrease in the relative volumetric diffusion of the magnetic activity, whereas the volumetric ratio of V1ppm /V2ppm is almost constant for all the E4 cages.

The SHARK integral generation and digestion system.

In this paper, the SHARK integral generation and digestion engine is described. In essence, SHARK is based on a reformulation of the popular McMurchie/Davidson approach to molecular integrals. This reformulation leads to an efficient algorithm that is driven by BLAS level 3 operations. The algorithm is particularly efficient for high angular momentum basis functions (up to L=7 is available by default, but the algorithm is programmed for arbitrary angular momenta). SHARK features a significant number of specific programming constructs that are designed to greatly simplify the workflow in quantum chemical program development and avoid undesirable code duplication to the largest possible extent. SHARK can handle segmented, generally and partially generally contracted basis sets. It can be used to generate a host of one- and two-electron integrals over various kernels including, two-, three-, and four-index repulsion integrals, integrals over Gauge Including Atomic Orbitals (GIAOs), relativistic integrals and integrals featuring a finite nucleus model. SHARK provides routines to evaluate Fock like matrices, generate integral transformations and related tasks. SHARK is the essential engine inside the ORCA package that drives essentially all tasks that are related to integrals over basis functions in version ORCA 5.0 and higher. Since the core of SHARK is based on low-level basic linear algebra (BLAS) operations, it is expected to not only perform well on present day but also on future hardware provided that the hardware manufacturer provides a properly optimized BLAS library for matrix and vector operations. Representative timings and comparisons to the Libint library used by ORCA are reported for Intel i9 and Apple M1 max processors.

Chemical Constituents from the Roots and Rhizomes of Sophora tonkinensis and Their Effects on Proprotein Convertase Substilisin/Kexin Type 9 Expression.

This study was conducted to further investigate bioactive molecules from Sophora tonkinensis that can inhibit proprotein convertase substilisin/kexin type 9 (PCSK9) expression. After interpreting NMR spectroscopic data and MS spectral data of all isolates, a new naturally occurring compound, 6-hydroxy-vitexin-2″-O-rhamnoside (7), was identified along with 30 known compounds. The calculation of the gauge-including atomic orbital (GAIO) and electronic circular dichroism (ECD) proposed the absolute configuration of 17 as (2S,3R)-methyl-2-(4-hydroxybenzyl)tartrate by comparing the calculated ECD with experimental data. All isolates were tested for their inhibitory effects on PCSK9 mRNA expression. Of the tested compounds, (+)-isolariciresinol (12) inhibited PCSK9 expression via downregulation of HNF1α and SREBPs.

Accurate Prediction of Nuclear Magnetic Resonance Parameters via the XYG3 Type of Doubly Hybrid Density Functionals.

Nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful and versatile tools in elucidating molecular structures. To eliminate ambiguities of experimental assignments, accurate calculations of NMR spectra are of great importance. Here, a method for theoretical evaluation of the NMR shielding constants by analytic derivatives using gauge including atomic orbitals (GIAO) has been implemented for the XYG3 type of doubly hybrid density functionals (xDH), namely, the GIAO-xDH method. Benchmark calculations on shielding constants and chemical shifts demonstrate the remarkable accuracy of the GIAO-xDH method, compared to the accurate CCSD(T) references. It is shown here that the XYGJ-OS functional is able to give a mean absolute deviation (MAD) of ∼3.0 ppm in the calculated shielding constants for 13C, 15N, 17O, 19F, while both XYGJ-OS and xDH-PBE0 functionals are able to provide a satisfactory estimation of chemical shifts with MADs of ∼0.03 and 1.0 ppm for 1H and 13C, respectively. The basis set influence upon the method has been examined and a computational scheme considering both accuracy and efficiency has been proposed and tested to predict the experimental 13C chemical shifts of five medium-sized natural product molecules, yielding a MAD of ∼1.0 ppm, which demonstrates the practical feasibility of the GIAO-xDH method.

Implementation of Nuclear Velocity Perturbation and Magnetic Field Perturbation Theory in CP2K and Their Application to Vibrational Circular Dichroism

We present the implementation of nuclear velocity perturbation theory (NVPT), using a pioneering combination of atom-centered (velocity-dependent) Gaussian basis functions and plane waves in the CP2K package. The atomic polar tensors (APTs) and atomic axial tensors (AATs) are evaluated in the velocity representation using efficient density functional perturbation theory. The presence of nonlocal pseudopotentials, the representation of potentials on numerical integration grids, and effects arising from the basis functions being centered on the atoms have been considered in the implementation. The Magnetic Field Perturbation Theory (MFPT) using gauge-including atomic orbitals is implemented in the same code and compared to the NVPT. Our implementation is the first to compare both approaches (MFPT and NVPT) in the same code. The implementation has been verified via sum rules and by investigating the gauge origin dependence of the AATs for a set of small molecules, oxirane, and fluoro-oxirane. We also present vibrational circular dichroism spectra that are related to the APTs and AATs, applying both theories.

Quasi-Relativistic Calculation of EPR g Tensors with Derivatives of the Decoupling Transformation, Gauge-Including Atomic Orbitals, and Magnetic Balance

We present an exact two-component (X2C) ansatz for the EPR g tensor using gauge-including atomic orbitals (GIAOs) and a magnetically balanced basis set expansion. In contrast to previous X2C and four-component relativistic ansätze for the g tensor, this implementation results in a gauge-origin-invariant formalism. Furthermore, the derivatives of the relativistic decoupling matrix are incorporated to form the complete analytical derivative of the X2C Hamiltonian. To reduce the associated computational costs, we apply the diagonal local approximation to the unitary decoupling transformation (DLU). The quasi-relativistic X2C and DLU-X2C Hamiltonians accurately reproduce the results of the parent four-component relativistic theory when accounting for two-electron picture-change effects with the modified screened nuclear spin-orbit approximation in the respective one-electron integrals and integral derivatives. According to our benchmark studies, the uncontracted Dyall and segmented-contracted Karlsruhe x2c-type basis sets perform well when compared to large even-tempered basis sets. Moreover, (range-separated) hybrid density functional approximations such as LC-ωPBE and ωB97X-D are needed to match the experimental findings. The impact of the GIAOs depends on the distribution of the spin density, and their use may change the Δg shifts by 10-50% as shown for [(C5Me5)2Y(μ-S)2Mo(μ-S)2Y(C5Me5)2]-. Routine calculations of large molecules are possible with widely available and comparably low-cost hardware as demonstrated for [Pt(C6Cl5)4]- with 3003 basis functions and three spin-(1/2) La(II) and Lu(II) compounds, for which we observe good agreement with the experimental findings.

Investigation of the interionic interactions and spectroscopic features of 1-Octyl-3-methylimidazolium chloride, tetrafluoroborate, and hexafluorophosphate ionic liquids: An experimental survey and DFT modeling

This study presents the spectroscopic and electronic properties of some imidazole-based ionic liquids (ILs) consisting of 1-Octyl-3-methylimidazolium cation and chloride, tetrafluoroborate, and hexafluorophosphate anions from experimental and theoretical perspectives. The ground state structural and vibrational characteristics of the ionic liquids have been achieved through Density Functional Theory (DFT) calculations at the Becke's and the Lee–Yang–Parr (B3LYP) and 6–311++G(d,p) level of theory in Gaussian 16. The electronic and magnetic features of the ILs have been examined by using electronic absorption spectra and Nuclear Magnetic Resonance spectroscopy (NMR) techniques along with the calculations from Time-Dependent Density Functional Theory (TD-DFT) and using Gauge-Including Atomic Orbital (GIAO) method.The intra- and interionic noncovalent interactions in the ionic liquids have been revealed via the electron density analysis based on the Atoms in Molecules (AIM) approach, and decomposed as hydrogen bonding, van der Waals interactions, and steric effects via Reduced Density Gradient (RDG) analysis. To gain insight into the possible effects of anion-cation interaction on the physicochemical properties of ionic liquids, interionic interactions, reactivity properties, topological critical points, and electrostatic potential surfaces were obtained. These interactional characteristics were interpreted in terms of both the anion dependency and interaction type. Notably, the results of this study were evaluated together with the results obtained from our previous study on ILs consisting of the same anions with the 1-Hexyl-3-methylimidazolium cation to achieve the effects of the extension in the chain length of the cation in the presence of the same anion on the spectroscopic and electronic properties of ionic liquids.

Isolation, Identification, Spectral Studies and X-ray Crystal Structures of Two Compounds from Bixa orellana, DFT Calculations and DNA Binding Studies

4,6-Diacetylresorcinol (1) and 3-O-methylellagic acid dihydrate (2), both biologically significant compounds, were extracted from Bixa orellana and studied using IR, 1H, and 13C NMR, and UV-vis spectroscopic techniques. X-ray crystallographic techniques were also used to establish the molecular structure of the isolated compounds 1 and 2. Geometric parameters, vibrational frequencies, and gauge including atomic orbital (GIAO) 1H and 13C NMR of 1 and 2 in the ground state were computed by the density functional theory (DFT) using B3LYP/6-311G(d,p) basis set backing up experimental studies and established the correct structure of isolated compounds. The parameters obtained from the combined DFT, and X-ray diffraction studies are mutually agreed to establish correct structures of 1 and 2. In addition, an electrostatic potential map and HOMO−LUMO energy gap were made using the DFT calculation to determine the distribution of energy and the chemical reactivity region of the isolated compounds. The current study also provides further insights into the interaction of compound 2 with ct-DNA using numerous biophysical and in silico techniques. Moreover, in silico studies indicate that compound 2 binds to the DNA in the minor groove. Lipinski’s rule of five revealed a higher tendency of compound 2 towards drug-likeness. The bioavailability and synthetic accessibility score for compound 2 was found to be 0.55 and 3.21, suggesting that compound 2 could serve as an effective therapeutic candidate.

Basis Set Dependence of Optical Rotation Calculations with Different Choices of Gauge.

In this work, the basis set dependence of optical rotation (OR) calculations is examined for various choices of gauge/level of theory. The OR is calculated for a set of 50 molecules using B3LYP and CAM-B3LYP and 17 molecules using coupled cluster with single and double excitations (CCSD). The calculations employ the correlation-consistent basis sets, aug-cc-pVζZ with ζ = D, T, Q. An inverse-power extrapolation formula is then utilized to obtain OR values at the complete basis set (CBS) limit. We investigate the basis set convergence for these methods and three choices of gauge: length gauge (with gauge-including atomic orbitals, LG(GIAOs), for DFT), the origin-invariant length gauge [LG(OI)], and the modified velocity gauge (MVG). The results show that all methods converge smoothly to the CBS limit and that the LG(OI) approach has a slightly faster convergence rate than the other choices of gauge. While the DFT methods reach gauge invariance at the CBS limit, CCSD does not. The significant difference between the MVG and LG(OI) results at the CBS limit, 26%, indicates that CCSD is not quite at convergence in the description of electron correlation for this property. On the other hand, gauge invariance at the CBS limit for DFT does not lead to the same OR values for the two density functionals, which is also due to electron correlation incompleteness. A limited comparison to gas-phase experimental OR values for the DFT methods shows that CAM-B3LYP seems more accurate than B3LYP. Overall, this study shows that the LG(OI) approach with the aug-cc-pVTZ basis set for DFT, and with the CBS(DT) extrapolation for CCSD, provides a good cost/accuracy balance.

Theoretical Investigation on Inclusion Complex of (s)-2-Isopropyl-1-(o-nitrophenyl) Sulfonyl) Aziridine with β-Cyclodextrin

The present work aims to study the theoretical chemistry applied to organic systems such as host / guest inclusion complexes. In literature different molecular modeling computation methods have been used to study the complexation of the host β-cyclodextrin molecule, with the guest (S) -2-Isopropyl-1- (o-nitrophenyl) sulfonyl) aziridine molecule, as semi-empirical PM3 and DFT (Density Functional Theory) calculations in gas and aqueous phases. The present paper focus on complexation, interaction and deformation energies determination, besides geometries, electronic structure, and chemical reactivity in order to describe the changes that AZ during encapsulation in two phases and two orientations. The results obtained with the Long-range corrected hybrid functional (WB97X-D / Base 6-31G (d))clearly indicate that the formed complex is energetically preferred in both phases, and the inclusion complex in the orientation A is more favorable than in the orientation B and shows good compatibility with the experimental results. NBO and NCI analysis were performed on the β - CD / AZ complex to understand the different interactions. The 1H nuclear magnetic resonance (NMR) of the complex was studied using the Gauge-Including Atomic Orbital (GIAO).

Cholesky decomposition of complex two-electron integrals over GIAOs: Efficient MP2 computations for large molecules in strong magnetic fields.

In large-scale quantum-chemical calculations, the electron-repulsion integral (ERI) tensor rapidly becomes the bottleneck in terms of memory and disk space. When an external finite magnetic field is employed, this problem becomes even more pronounced because of the reduced permutational symmetry and the need to work with complex integrals and wave function parameters. One way to alleviate the problem is to employ a Cholesky decomposition (CD) to the complex ERIs over gauge-including atomic orbitals. The CD scheme establishes favorable compression rates by selectively discarding linearly dependent product densities from the chosen basis set while maintaining a rigorous and robust error control. This error control constitutes the main advantage over conceptually similar methods such as density fitting, which relies on employing pre-defined auxiliary basis sets. We implemented the use of the CD in the framework of finite-field (ff) Hartree-Fock and ff second-order Møller-Plesset perturbation theory (MP2). Our work demonstrates that the CD compression rates are particularly beneficial in calculations in the presence of a finite magnetic field. The ff-CD-MP2 scheme enables the correlated treatment of systems with more than 2000 basis functions in strong magnetic fields within a reasonable time span.

The Investigation of Spectroscopic and Electronic Properties of 3-Ethyl-4-(4-cinnamoyloxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-one Compound Using Density Functional Theory and Hartree-Fock Basis Sets

In this study, we reported a combined experimental and theoretical study on 3-n-propyl-4-(3-cinnamoyloxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-one compound. The title compound was prepared and characterized by Uv-Vis, FT-IR spectra, 1H and 13C NMR. UV-visible absorption spectra and the stimulation contributions in UV-visible transitions were obtained with TD-DFT/B3LYP and TD-FF methods and 6-311G(d) polarizer set based on optimized structure. Calculated absorption wavelengths (λ), oscillator power (f) and excitation energies were compared with experimental values. The calculated IR data of compound were calculated in gas phase by using of 6-31G(d) basis set of B3LYP and HF methods and are multiplied with appropriate scala factors. Theoretical infrared spectrums are formed from the data obtained according to B3LYP method. In the identification of calculated IR data was used the veda4f program. The molecular geometry, gauge including atomic orbital (GIAO), Experimental and theoretical values were inserted into the graphic according to equitation of δexp=a+b. δ calc. The standard error values were found via SigmaPlot program with regression coefficient of a and b constants. Obtained results indicate that there is a good agreement between the experimental and theoretical data. Also, HOMO-LUMO analyses properties, Mulliken’s atomic charges, dipole moment and total energy of the title compound in the ground state were investigated by using Hartree-Fock (HF) and density functional theory (DFT/B3LYP) methods with 6-31G(d) basic set.

1H NMR spectra, structure, and conformational exchange of S-n-alkyl-tetrahydrothiophenium cations of some ionic liquids

S-n-alkyl-tetrahydrothiophenium cations [R-THT]+ in some iodide or tetraphenylborate ion-pairs [R-THT][X] (R = methyl to n-decyl, X−= I−, [BPh4]−, [NTf2]−) are characterized in the solid state by puckered THT rings in twist forms. In contrast, solution 1H NMR spectra of compounds [R-THT][X] indicate a rapid conformational exchange leading to dynamic [ABCD]2 spin systems due to eight protons of the THT ring. These strongly coupled spectra obtained at high magnetic fields were analyzed by iterative methods and simulated successfully. In addition, molecular modeling and gauge-including atomic orbitals (GIAOs) based calculations of proton NMR chemical shifts for two such ion-pair compounds in solution were performed at the density functional theory (DFT) level . As a result, conformational equilibrium between two different pairs of isoenergetic twist forms of the THT ring in [Me-THT][I] (global and local energy minima) was found to exist. These theoretical results are discussed in view of experimental 1H NMR spectral data.

Fast and Accurate Electric Field Gradient Calculations in Molecular Solids With Density Functional Theory.

Modern approaches for calculating electric field gradient (EFF) tensors in molecular solids rely upon plane-wave calculations employing periodic boundary conditions (PBC). In practice, models employing PBCs are limited to generalized gradient approximation (GGA) density functionals. Hybrid density functionals applied in the context of gauge-including atomic orbital (GIAO) calculations have been shown to substantially improve the accuracy of predicted NMR parameters. Here we propose an efficient method that effectively combines the benefits of both periodic calculations and single-molecule techniques for predicting electric field gradient tensors in molecular solids. Periodic calculations using plane-wave basis sets were used to model the crystalline environment. We then introduce a molecular correction to the periodic result obtained from a single-molecule calculation performed with a hybrid density functional. Single-molecule calculations performed using hybrid density functionals were found to significantly improve the agreement of predicted 17O quadrupolar coupling constants (C q ) with experiment. We demonstrate a 31% reduction in the RMS error for the predicted 17O C q values relative to standard plane-wave methods using a carefully constructed test set comprised of 22 oxygen-containing molecular crystals. We show comparable improvements in accuracy using five different hybrid density functionals and find predicted C q values to be relatively insensitive to the choice of basis set used in the single molecule calculation. Finally, the utility of high-accuracy 17O C q predictions is demonstrated by examining the disordered 4-Nitrobenzaldehyde crystal structure.