Can simple 'molecular' corrections outperform projector augmented-wave density functional theory in the prediction of 35 Cl electric field gradient tensor parameters for chlorine-containing crystalline systems?

Many-body expansion (MBE) fragment approaches have been applied to accurately compute nuclear magnetic resonance (NMR) parameters in crystalline systems. Recent examples demonstrate that electric field gradient (EFG) tensor parameters can be accurately calculated for 14 N and 17 O. A key additional development is the simple molecular correction (SMC) approach, which uses two one-body fragment (i.e., isolated molecule) calculations to adjust NMR parameter values established using 'benchmark' projector augmented-wave (PAW) density functional theory (DFT) values. Here, we apply a SMC using the hybrid PBE0 exchange-correlation (XC) functional to see if this can improve the accuracy of calculated 35 Cl EFG tensor parameters. We selected eight organic and two inorganic crystal structures and considered 15 chlorine sites. We find that this SMC improves the accuracy of computed values for both the 35 Cl quadrupolar coupling constant (CQ ) and the asymmetry parameter ( η Q ) by approximately 30% compared with benchmark PAW DFT values. We also assessed a SMC that offers local improvements not only in terms of the quality of the XC functional but simultaneously in the quality of the description of relativistic effects via the inclusion of spin-orbit effects. As the inorganic systems considered contain heavy atoms bonded to the chlorine atoms, we find further improvements in the accuracy of calculated 35 Cl EFG tensor parameters when both a hybrid functional and spin-orbit effects are included in the SMC. On the contrary, for chlorine-containing organics, the inclusion of spin-orbit relativistic effects using a SMC does not improve the accuracy of computed 35 Cl EFG tensor parameters.

Multiple Surface Site Three-Dimensional Structure Determination of a Supported Molecular Catalyst.

The structural characterization of supported molecular catalysts is challenging due to the low density of active sites and the presence of several organic/organometallic surface groups resulting from the often complex surface chemistry associated with support functionalization. Here, we provide a complete atomic-scale description of all surface sites in an N-heterocyclic carbene based on iridium and supported on silica, at all stages of its synthesis. By combining a suitable isotope labeling strategy with the implementation of multinuclear dipolar recoupling DNP-enhanced NMR experiments, the 3D structure of the Ir-NHC sites, as well as that of the synthesis intermediates were determined. As a significant fraction of parent surface fragments does not react during the multistep synthesis, site-selective experiments were implemented to specifically probe proximities between the organometallic groups and the solid support. The NMR-derived structure of the iridium sites points to a well-defined conformation. By interpreting EXAFS spectroscopy and chemical analysis data augmented by computational studies, the presence of two coordination geometries is demonstrated: Ir-NHC fragments coordinated by a 1,5-cyclooctadiene and one Cl ligand, as well as, more surprisingly, a fragment coordinated by two NHC and two Cl ligands. This study demonstrates a unique methodology to disclose individual surface structures in complex, multisite environments, a long-standing challenge in the field of heterogeneous/supported catalysts, while revealing new, unexpected structural features of metallo-NHC-supported substrates. It also highlights the potentially large diversity of surface sites present in functional materials prepared by surface chemistry, an essential knowledge to design materials with improved performances.

Resolving alternative organic crystal structures using density functional theory and NMR chemical shifts.

Alternative ('repeat') determinations of organic crystal structures deposited in the Cambridge Structural Database are analysed to characterise the nature and magnitude of the differences between structure solutions obtained by diffraction methods. Of the 3132 structure pairs considered, over 20% exhibited local structural differences exceeding 0.25 Å. In most cases (about 83%), structural optimisation using density functional theory (DFT) resolved the differences. Many of the cases where distinct and chemically significant structural differences remained after optimisation involved differently positioned hydroxyl groups, with obvious implications for the correct description of hydrogen bonding. 1H and 13C chemical shifts from solid-state NMR experiments are proposed as an independent methodology in cases where DFT optimisation fails to resolve discrepancies.

Rapid Structure Determination of Molecular Solids Using Chemical Shifts Directed by Unambiguous Prior Constraints.

NMR-based crystallography approaches involving the combination of crystal structure prediction methods, ab initio calculated chemical shifts and solid-state NMR experiments are powerful methods for crystal structure determination of microcrystalline powders. However, currently structural information obtained from solid-state NMR is usually included only after a set of candidate crystal structures has already been independently generated, starting from a set of single-molecule conformations. Here, we show with the case of ampicillin that this can lead to failure of structure determination. We propose a crystal structure determination method that includes experimental constraints during conformer selection. In order to overcome the problem that experimental measurements on the crystalline samples are not obviously translatable to restrict the single-molecule conformational space, we propose constraints based on the analysis of absent cross-peaks in solid-state NMR correlation experiments. We show that these absences provide unambiguous structural constraints on both the crystal structure and the gas-phase conformations, and therefore can be used for unambiguous selection. The approach is parametrized on the crystal structure determination of flutamide, flufenamic acid, and cocaine, where we reduce the computational cost by around 50%. Most importantly, the method is then shown to correctly determine the crystal structure of ampicillin, which would have failed using current methods because it adopts a high-energy conformer in its crystal structure. The average positional RMSE on the NMR powder structure is ⟨rav⟩ = 0.176 Å, which corresponds to an average equivalent displacement parameter Ueq = 0.0103 Å2.

Elucidating an Amorphous Form Stabilization Mechanism for Tenapanor Hydrochloride: Crystal Structure Analysis Using X-ray Diffraction, NMR Crystallography, and Molecular Modeling.

By the combined use of powder and single-crystal X-ray diffraction, solid-state NMR, and molecular modeling, the crystal structures of two systems containing the unusually large tenapanor drug molecule have been determined: the free form, ANHY, and a dihydrochloride salt form, 2HCl. Dynamic nuclear polarization (DNP) assisted solid-state NMR (SSNMR) crystallography investigations were found essential for the final assignment and were used to validate the crystal structure of ANHY. From a structural informatics analysis of ANHY and 2HCl, conformational ring differences in one part of the molecule were observed which influence the relative orientation of a methyl group on a ring nitrogen and thereby impact the crystallizability of the dihydrochloride salt. From quantum chemistry calculations, the dynamics between different ring conformations in tenapanor is predicted to be fast. Addition of HCl to tenapanor results in general in a mixture of protonated ring conformers and hence a statistical mix of diastereoisomers which builds up the amorphous form, a-2HCl. This was qualitatively verified by 13C CP/MAS NMR investigations of the amorphous form. Thus, to form any significant amount of the crystalline material 2HCl, which originates from the minor (i.e., energetically less stable) ring conformations, one needs to involve nitrogen deprotonation to allow exchange between the minor and major conformations of ANHY in solution. Thus, by controlling the solution pH value to well below the p Ka of ANHY, the equilibrium between ANHY and 2HCl can be controlled and by this mechanism the crystallization of 2HCl can be avoided and the amorphous form of the dichloride salt can therefore be stabilized.

Structural Insights from 59 Co Solid-State NMR Experiments on Organocobalt(I) Catalysts.

A series of fumarate-based organocobalt(I) [CoCp(CO)(fumarate)] catalysts is synthesized and characterized by X-ray crystallography, multinuclear (13 C and 59 Co) solid-state NMR spectroscopy, and 59 Co NQR spectroscopy. Given the dearth of 59 Co solid-state NMR studies on CoI compounds, the present work constitutes the first systematic characterization of the 59 Co electric field gradient and chemical shift tensors for a series of cobalt complexes in this oxidation state. Using X-ray crystallography, the molecular geometry about the CoI centre is found to be nearly identical in all compounds studied herein. Owing to the 59 Co nucleus' large chemical shift range, solid-state NMR experiments are found to be able to detect small structural differences between the individual organocobalt(I) compounds. With the aid of density functional theory calculations on these complexes, it is shown that the 59 Co chemical shift anisotropy and the 59 Co quadrupolar coupling constant are both extremely sensitive gauges of the Fu-Co-Cp bond angle, providing a link between these 59 Co NMR observables and the catalysts' structures.

The structure and binding mode of citrate in the stabilization of gold nanoparticles.

Elucidating the binding mode of carboxylate-containing ligands to gold nanoparticles (AuNPs) is crucial to understand their stabilizing role. A detailed picture of the three-dimensional structure and coordination modes of citrate, acetate, succinate and glutarate to AuNPs is obtained by 13C and 23Na solid-state NMR in combination with computational modelling and electron microscopy. The binding between the carboxylates and the AuNP surface is found to occur in three different modes. These three modes are simultaneously present at low citrate to gold ratios, while a monocarboxylate monodentate (1κO1) mode is favoured at high citrate:gold ratios. The surface AuNP atoms are found to be predominantly in the zero oxidation state after citrate coordination, although trace amounts of Auδ+ are observed. 23Na NMR experiments show that Na+ ions are present near the gold surface, indicating that carboxylate binding occurs as a 2e- L-type interaction for each oxygen atom involved. This approach has broad potential to probe the binding of a variety of ligands to metal nanoparticles.

Does Z' equal 1 or 2? Enhanced powder NMR crystallography verification of a disordered room temperature crystal structure of a p38 inhibitor for chronic obstructive pulmonary disease.

The crystal structure of the Form A polymorph of N-cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxo-pyrazin-1-yl]benzamide (i.e., AZD7624), determined using single-crystal X-ray diffraction (scXRD) at 100 K, contains two molecules in the asymmetric unit (Z' = 2) and has regions of local static disorder. This substance has been in phase IIa drug development trials for the treatment of chronic obstructive pulmonary disease, a disease which affects over 300 million people and contributes to nearly 3 million deaths annually. While attempting to verify the crystal structure using nuclear magnetic resonance crystallography (NMRX), we measured 13C solid-state NMR (SSNMR) spectra at 295 K that appeared consistent with Z' = 1 rather than Z' = 2. To understand this surprising observation, we used multinuclear SSNMR (1H, 13C, 15N), gauge-including projector augmented-wave density functional theory (GIPAW DFT) calculations, crystal structure prediction (CSP), and powder XRD (pXRD) to determine the room temperature crystal structure. Due to the large size of AZD7624 (ca. 500 amu, 54 distinct 13C environments for Z' = 2), static disorder at 100 K, and (as we show) dynamic disorder at ambient temperatures, NMR spectral assignment was a challenge. We introduce a method to enhance confidence in NMR assignments by comparing experimental 13C isotropic chemical shifts against site-specific DFT-calculated shift distributions established using CSP-generated crystal structures. The assignment and room temperature NMRX structure determination process also included measurements of 13C shift tensors and the observation of residual dipolar coupling between 13C and 14N. CSP generated ca. 90 reasonable candidate structures (Z' = 1 and Z' = 2), which when coupled with GIPAW DFT results, room temperature pXRD, and the assigned SSNMR data, establish Z' = 2 at room temperature. We find that the polymorphic Form A of AZD7624 is maintained at room temperature, although dynamic disorder is present on the NMR timescale. Of the CSP-generated structures, 2 are found to be fully consistent with the SSNMR and pXRD data; within this pair, they are found to be structurally very similar (RMSD16 = 0.30 Å). We establish that the CSP structure in best agreement with the NMR data possesses the highest degree of structural similarity with the scXRD-determined structure (RMSD16 = 0.17 Å), and has the lowest DFT-calculated energy amongst all CSP-generated structures with Z' = 2.

Exploring Systematic Discrepancies in DFT Calculations of Chlorine Nuclear Quadrupole Couplings.

Previous studies have revealed significant discrepancies between density functional theory (DFT)-calculated and experimental nuclear quadrupolar coupling constants (CQ) for chlorine atoms, particularly in ionic solids. Various aspects of the computations are systematically investigated here, including the choice of the DFT functional, basis set convergence, and geometry optimization protocol. The effects of fast (fs) time-scale dynamics are probed using molecular dynamics (MD) and nuclear quantum effects (NQEs) are considered using path-integral MD calculations. It is shown that the functional choice is the most important factor related to improving the accuracy of the quadrupolar coupling calculations, and that functionals beyond the generalized gradient approximation (GGA) level, such as hybrid and meta-GGA functionals, are required for good correlations with experiment. The influence of molecular dynamics and NQEs is less important than the functional choice in the studied systems. A method which involves scaling the calculated quadrupolar coupling constant is proposed here; its application leads to good agreement with experimental data.

Three-Dimensional Structure Determination of Surface Sites.

The spatial arrangement of atoms is directly linked to chemical function. A fundamental challenge in surface chemistry and catalysis relates to the determination of three-dimensional structures with atomic-level precision. Here we determine the three-dimensional structure of an organometallic complex on an amorphous silica surface using solid-state NMR measurements, enabled through a dynamic nuclear polarization surface enhanced NMR spectroscopy approach that induces a 200-fold increase in the NMR sensitivity for the surface species. The result, in combination with EXAFS, is a detailed structure for the surface complex determined with a precision of 0.7 Å. We observe a single well-defined conformation that is folded toward the surface in such a way as to include an interaction between the platinum metal center and the surface oxygen atoms.

Furosemide's one little hydrogen atom: NMR crystallography structure verification of powdered molecular organics.

The potential of NMR crystallography to verify molecular crystal structures deposited in structural databases is evaluated, with two structures of the pharmaceutical furosemide serving as examples. While the structures differ in the placement of one H atom, using this approach, we verify one of the structures in the Cambridge Structural Database using quantitative tools, while establishing that the other structure does not meet the verification criteria.

Controlling the hydrogenolysis of silica-supported tungsten pentamethyl leads to a class of highly electron deficient partially alkylated metal hydrides.

The well-defined single-site silica-supported tungsten complex [([triple bond, length as m-dash]Si-O-)W(Me)5], 1, is an excellent precatalyst for alkane metathesis. The unique structure of 1 allows the synthesis of unprecedented tungsten hydrido methyl surface complexes via a controlled hydrogenolysis. Specifically, in the presence of molecular hydrogen, 1 is quickly transformed at -78 °C into a partially alkylated tungsten hydride, 4, as characterized by 1H solid-state NMR and IR spectroscopies. Species 4, upon warming to 150 °C, displays the highest catalytic activity for propane metathesis yet reported. DFT calculations using model systems support the formation of [([triple bond, length as m-dash]Si-O-)WH3(Me)2], as the predominant species at -78 °C following several elementary steps of hydrogen addition (by σ-bond metathesis or α-hydrogen transfer). Rearrangement of 4 occuring between -78 °C and room temperature leads to the formation of an unique methylidene tungsten hydride [([triple bond, length as m-dash]Si-O-)WH3([double bond, length as m-dash]CH2)], as determined by solid-state 1H and 13C NMR spectroscopies and supported by DFT. Thus for the first time, a coordination sphere that incorporates both carbene and hydride functionalities has been observed.

Na(+) mobility in sodium strontium silicate fast ion conductors.

We present the first direct evidence of Na-ion mobility in sodium strontium silicate fast ion conductors, based on variable temperature (23)Na solid state NMR spectroscopy and spin-lattice relaxation measurements.

Polymorphs of Theophylline Characterized by DNP Enhanced Solid-State NMR.

We show how dynamic nuclear polarization (DNP) enhanced solid-state NMR spectroscopy can be used to characterize polymorphs and solvates of organic solids. We applied DNP to three polymorphs and one hydrated form of the asthma drug molecule theophylline. For some forms of theophylline, sample grinding and impregnation with the radical-containing solution, which are necessary to prepare the samples for DNP, were found to induce polymorphic transitions or desolvation between some forms. We present protocols for sample preparation for solid-state magic-angle spinning (MAS) DNP experiments that avoid the polymorphic phase transitions in theophylline. These protocols include cryogrinding, grinding under inert atmosphere, and the appropriate choice of the impregnating liquid. By applying these procedures, we subsequently demonstrate that two-dimensional correlation experiments, such as (1)H-(13)C and (1)H-(15)N HETCOR or (13)C-(13)C INADEQUATE, can be obtained at natural isotopic abundance in reasonable times, thus enabling more advanced structural characterization of polymorphs.

Cooperative Effect of Monopodal Silica-Supported Niobium Complex Pairs Enhancing Catalytic Cyclic Carbonate Production.

Recent discoveries highlighted the activity and the intriguing mechanistic features of NbCl5 as a molecular catalyst for the cycloaddition of CO2 and epoxides under ambient conditions. This has inspired the preparation of novel silica-supported Nb species by reacting a molecular niobium precursor, [NbCl5·OEt2], with silica dehydroxylated at 700 °C (SiO(2-700)) or at 200 °C (SiO(2-200)) to generate diverse surface complexes. The product of the reaction between SiO(2-700) and [NbCl5·OEt2] was identified as a monopodal supported surface species, [≡SiONbCl4·OEt2] (1a). The reactions of SiO(2-200) with the niobium precursor, according to two different protocols, generated surface complexes 2a and 3a, presenting significant, but different, populations of the monopodal surface complex along with bipodal [(≡SiO)2NbCl3·OEt2]. (93)Nb solid-state NMR spectra of 1a-3a and (31)P solid-state NMR on their PMe3 derivatives 1b-3b led to the unambiguous assignment of 1a as a single-site monopodal Nb species, while 2a and 3a were found to present two distinct surface-supported components, with 2a being mostly monopodal [≡SiONbCl4·OEt2] and 3a being mostly bipodal [(≡SiO)2NbCl3·OEt2]. A double-quantum/single-quantum (31)P NMR correlation experiment carried out on 2b supported the existence of vicinal Nb centers on the silica surface for this species. 1a-3a were active heterogeneous catalysts for the synthesis of propylene carbonate from CO2 and propylene oxide under mild catalytic conditions; the performance of 2a was found to significantly surpass that of 1a and 3a. With the support of a systematic DFT study carried out on model silica surfaces, the observed differences in catalytic efficiency were correlated with an unprecedented cooperative effect between two neighboring Nb centers on the surface of 2a. This is in an excellent agreement with our previous discoveries regarding the mechanism of NbCl5-catalyzed cycloaddition in the homogeneous phase.

Solid-state (185/187)Re NMR and GIPAW DFT study of perrhenates and Re2(CO)10: chemical shift anisotropy, NMR crystallography, and a metal-metal bond.

Advances in solid-state nuclear magnetic resonance (SSNMR) methods, such as dynamic nuclear polarization (DNP), intricate pulse sequences, and increased applied magnetic fields, allow for the study of systems which even very recently would be impractical. However, SSNMR methods using certain quadrupolar probe nuclei (i.e., I > 1/2), such as (185/187)Re remain far from fully developed due to the exceedingly strong interaction between the quadrupole moment of these nuclei and local electric field gradients (EFGs). We present a detailed high-field (B0 = 21.1 T) experimental SSNMR study on several perrhenates (KReO4, AgReO4, Ca(ReO4)2·2H2O), as well as ReO3 and Re2(CO)10. We propose solid ReO3 as a new rhenium SSNMR chemical shift standard due to its reproducible and sharp (185/187)Re NMR resonances. We show that for KReO4, previously poorly understood high-order quadrupole-induced effects (HOQIE) on the satellite transitions can be used to measure the EFG tensor asymmetry (i.e., ηQ) to nearly an order-of-magnitude greater precision than competing SSNMR and nuclear quadrupole resonance (NQR) approaches. Samples of AgReO4 and Ca(ReO4)2·2H2O enable us to comment on the effects of counter-ions and hydration upon Re(vii) chemical shifts. Calcium-43 and (185/187)Re NMR tensor parameters allow us to conclude that two proposed crystal structures for Ca(ReO4)2·2H2O, which would be considered as distinct, are in fact the same structure. Study of Re2(CO)10 provides insights into the effects of Re-Re bonding on the rhenium NMR tensor parameters and rhenium oxidation state on the Re chemical shift value. As overtone NQR experiments allowed us to precisely measure the (185/187)Re EFG tensor of Re2(CO)10, we were able to measure rhenium chemical shift anisotropy (CSA) for the first time in a powdered sample. Experimental observations are supported by gauge-including projector augmented-wave (GIPAW) density functional theory (DFT) calculations, with NMR tensor calculations also provided for NH4ReO4, NaReO4 and RbReO4. These calculations are able to reproduce many of the experimental trends in rhenium δiso values and EFG tensor magnitudes. Using KReO4 as a prototypical perrhenate-containing system, we establish a correlation between the tetrahedral shear strain parameter (|ψ|) and the nuclear electric quadrupolar coupling constant (CQ), which enables the refinement of the structure of ND4ReO4. Shortcomings in traditional DFT approaches, even when including relativistic effects via the zeroth-order regular approximation (ZORA), for calculating rhenium NMR tensor parameters are identified for Re2(CO)10.

Calcium-43 chemical shift and electric field gradient tensor interplay: a sensitive probe of structure, polymorphism, and hydration.

Calcium is the 5th most abundant element on earth, and is found in numerous biological tissues, proteins, materials, and increasingly in catalysts. However, due to a number of unfavourable nuclear properties, such as a low magnetogyric ratio, very low natural abundance, and its nuclear electric quadrupole moment, development of solid-state (43)Ca NMR has been constrained relative to similar nuclides. In this study, 12 commonly-available calcium compounds are analyzed via(43)Ca solid-state NMR and the information which may be obtained by the measurement of both the (43)Ca electric field gradient (EFG) and chemical shift tensors (the latter of which are extremely rare with only a handful of literature examples) is discussed. Combined with density functional theory (DFT) computations, this 'tensor interplay' is, for the first time for (43)Ca, illustrated to be diagnostic in distinguishing polymorphs (e.g., calcium formate), and the degree of hydration (e.g., CaCl2·2H2O and calcium tartrate tetrahydrate). For Ca(OH)2, we outline the first example of (1)H to (43)Ca cross-polarization on a sample at natural abundance in (43)Ca. Using prior knowledge of the relationship between the isotropic calcium chemical shift and the calcium quadrupolar coupling constant (CQ) with coordination number, we postulate the coordination number in a sample of calcium levulinate dihydrate, which does not have a known crystal structure. Natural samples of CaCO3 (aragonite polymorph) are used to show that the synthetic structure is present in nature. Gauge-including projector augmented-wave (GIPAW) DFT computations using accepted crystal structures for many of these systems generally result in calculated NMR tensor parameters which are in very good agreement with the experimental observations. This combination of (43)Ca NMR measurements with GIPAW DFT ultimately allows us to establish clear correlations between various solid-state (43)Ca NMR observables and selected structural parameters, such as unit cell dimensions and average Ca-O bond distances.

Dynamic nuclear polarization enhanced NMR spectroscopy for pharmaceutical formulations.

Dynamic nuclear polarization (DNP) enhanced solid-state NMR spectroscopy at 9.4 T is demonstrated for the detailed atomic-level characterization of commercial pharmaceutical formulations. To enable DNP experiments without major modifications of the formulations, the gently ground tablets are impregnated with solutions of biradical polarizing agents. The organic liquid used for impregnation (here 1,1,2,2-tetrachloroethane) is chosen so that the active pharmaceutical ingredient (API) is minimally perturbed. DNP enhancements (ε) of between 40 and 90 at 105 K were obtained for the microparticulate API within four different commercial formulations of the over-the-counter antihistamine drug cetirizine dihydrochloride. The different formulations contain between 4.8 and 8.7 wt % API. DNP enables the rapid acquisition with natural isotopic abundances of one- and two-dimensional (13)C and (15)N solid-state NMR spectra of the formulations while preserving the microstructure of the API particles. Here this allowed immediate identification of the amorphous form of the API in the tablet. API-excipient interactions were observed in high-sensitivity (1)H-(15)N correlation spectra, revealing direct contacts between povidone and the API. The API domain sizes within the formulations were determined by measuring the variation of ε as a function of the polarization time and numerically modeling nuclear spin diffusion. Here we measure an API particle radius of 0.3 µm with a single particle model, while modeling with a Weibull distribution of particle sizes suggests most particles possess radii of around 0.07 µm.

WMe6 tamed by silica: ≡Si-O-WMe5 as an efficient, well-defined species for alkane metathesis, leading to the observation of a supported W-methyl/methylidyne species.

The synthesis and full characterization of a well-defined silica-supported ≡Si-O-W(Me)5 species is reported. Under an inert atmosphere, it is a stable material at moderate temperature, whereas the homoleptic parent complex decomposes above -20 °C, demonstrating the stabilizing effect of immobilization of the molecular complex. Above 70 °C the grafted complex converts into the two methylidyne surface complexes [(≡SiO-)W(≡CH)Me2] and [(≡SiO-)2W(≡CH)Me]. All of these silica-supported complexes are active precursors for propane metathesis reactions.

Multinuclear Solid-State Magnetic Resonance as a Sensitive Probe of Structural Changes upon the Occurrence of Halogen Bonding in Co-crystals.

Although the understanding of intermolecular interactions, such as hydrogen bonding, is relatively well-developed, many additional weak interactions work both in tandem and competitively to stabilize a given crystal structure. Due to a wide array of potential applications, a substantial effort has been invested in understanding the halogen bond. Here, we explore the utility of multinuclear ((13)C, (14/15)N, (19)F, and (127)I) solid-state magnetic resonance experiments in characterizing the electronic and structural changes which take place upon the formation of five halogen-bonded co-crystalline product materials. Single-crystal X-ray diffraction (XRD) structures of three novel co-crystals which exhibit a 1:1 stoichiometry between decamethonium diiodide (i.e., [(CH3)3N(+)(CH2)10N(+)(CH3)3][2 I(-)]) and different para-dihalogen-substituted benzene moieties (i.e., p-C6X2Y4, X=Br, I; Y=H, F) are presented. (13)C and (15)N NMR experiments carried out on these and related systems validate sample purity, but also serve as indirect probes of the formation of a halogen bond in the co-crystal complexes in the solid state. Long-range changes in the electronic environment, which manifest through changes in the electric field gradient (EFG) tensor, are quantitatively measured using (14)N NMR spectroscopy, with a systematic decrease in the (14)N quadrupolar coupling constant (CQ) observed upon halogen bond formation. Attempts at (127)I solid-state NMR spectroscopy experiments are presented and variable-temperature (19)F NMR experiments are used to distinguish between dynamic and static disorder in selected product materials, which could not be conclusively established using solely XRD. Quantum chemical calculations using the gauge-including projector augmented-wave (GIPAW) or relativistic zeroth-order regular approximation (ZORA) density functional theory (DFT) approaches complement the experimental NMR measurements and provide theoretical corroboration for the changes in NMR parameters observed upon the formation of a halogen bond.