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Planewave-corrected methods have proven effective for accurately modeling nuclear magnetic resonance (NMR) parameters in crystalline systems. Recent work extended the application of planewave-corrected calculations beyond the second row, predicting EFG tensor parameters for 35Cl using a simple molecular correction to projector augmented-wave (PAW) density functional theory (DFT). Here we extend this work using fragment and cluster-based calculations coupled with polarizable continuum (PCM) methods to improve further the accuracy of planewave-corrected 35Cl EFG tensor calculations. Benchmark data from a test set comprised of 105 individual 35Cl EFG tensor principal components for chlorine-containing molecular crystals and crystalline chloride salts shows fragment-corrected planewave calculations using the PBE0 hybrid density functional improve the accuracy of predicted EFG tensor components by 30 % relative to traditional planewave calculations. We compare the influence of different geometry optimization methods and density functionals on the accuracy of predicted 35Cl EFG tensor parameters. Four cases of spectral assignment are presented to demonstrate the utility of improving the accuracy of predicted 35Cl EFG tensor parameters.
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Solid-state nuclear magnetic resonance (NMR) spectroscopy and quantum chemical density functional theory (DFT) calculations are widely used to characterize vanadium centers in biological and pharmaceutically relevant compounds. Several techniques have been recently developed to improve the accuracy of predicted NMR parameters obtained from DFT. Fragment-based and planewave-corrected methods employing hybrid density functionals are particularly effective tools for solid-state applications. A recent benchmark study involving molecular crystal compounds found that fragment-based NMR calculations using hybrid density functionals improve the accuracy of predicted 51V chemical shieldings by 20% relative to traditional planewave methods. This work extends the previous study, including a careful analysis of 51V chemical shift anisotropy, electric field gradient calculations, and a more extensive test set. The accuracy of planewave-corrected techniques and recently developed fragment-based methods using electrostatic embedding based on the polarized continuum model (PCM) are found to be highly competitive with previous methods. Planewave-corrected methods achieve a 34% improvement in the errors of predicted 51V chemical shieldings relative to planewave. Additionally, planewave-corrected and fragment-based calculations were performed using PCM embedding, improving the accuracy of predicted 51V chemical shielding (CS) tensor principal values by 30% and C q values by 15% relative to traditional planewave methods. The performance of these methods is further examined using a redox-active oxovandium complex and a common 51V NMR reference compound.
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Ab initio predictions of chemical shifts and electric field gradient (EFG) tensor components are frequently used to help interpret solid-state nuclear magnetic resonance (NMR) experiments. Typically, these predictions employ density functional theory (DFT) with generalized gradient approximation (GGA) functionals, though hybrid functionals have been shown to improve accuracy relative to experiment. Here, the performance of a dozen models beyond the GGA approximation are examined for the prediction of solid-state NMR observables, including meta-GGA, hybrid, and double-hybrid density functionals and second-order Møller-Plesset perturbation theory (MP2). These models are tested on organic molecular crystal data sets containing 169 experimental 13C and 15N chemical shifts and 114 17O and 14N EFG tensor components. To make these calculations affordable, gauge-including projector augmented wave (GIPAW) Perdew-Burke-Ernzerhof (PBE) calculations with periodic boundary conditions are combined with a local intramolecular correction computed at the higher level of theory. Within the context of typical NMR property calculations performed on a static, DFT-optimized crystal structure, the benchmarking finds that the double-hybrid DFT functionals produce errors versus experiment that are no smaller than those of hybrid functionals in the best cases, and they can be larger. MP2 errors versus experiment are even bigger. Overall, no practical advantages are found for using any of the tested double-hybrid functionals or MP2 to predict experimental solid-state NMR chemical shifts and EFG tensor components for routine organic crystals, especially given the higher computational cost of those methods. This finding likely reflects error cancellation benefiting the hybrid functionals. Improving the accuracy of the predicted chemical shifts and EFG tensors relative to experiment would probably require more robust treatments of the crystal structures, their dynamics, and other factors.
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Nuclear quadrupole resonances for 14 N and 17 O nuclei are exquisitely sensitive to interactions with surrounding atoms. As a result, nitrogen and oxygen solid-state nuclear magnetic resonance (ssNMR) provides a powerful tool for investigating structure and dynamics in complex systems. First-principles calculations are increasingly used to facilitate spectral assignment and to evaluate and adjust crystal structures. Recent work combining the strengths of planewave density functional theory (DFT) calculations with a single molecule correction obtained using a higher level of theory has proven successful in improving the accuracy of predicted chemical shielding (CS) tensors and 17 O quadrupolar coupling constants ( C q ). Here we extend this work by examining the accuracy of predicted 14 N and 17 O electric field gradient (EFG) tensor components obtained using alternative planewave-corrections involving cluster and two-body fragment-based calculations. We benchmark the accuracy of CS and EFG tensor predictions for both nitrogen and oxygen using planewave, two-body fragment, and enhanced planewave-corrected techniques. Combining planewave and two-body fragment calculations reduces the error in predicted 17 O C q values by 35% relative to traditional planewave calculations. These enhanced planewave-correction methods improve the accuracy of 17 O and 14 N EFG tensor components by 15% relative to planewave DFT but yield minimal improvement relative to a simple molecular correction. However, in structural environments involving either high symmetry or strong intermolecular interactions, enhanced planewave-corrected methods provide a distinct advantage.
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Ab initio methods for predicting NMR parameters in the solid state are an essential tool for assigning experimental spectra and play an increasingly important role in structural characterizations. Recently, a molecular correction (MC) technique has been developed which combines the strengths of plane-wave methods (GIPAW) with single molecule calculations employing Gaussian basis sets. The GIPAW + MC method relies on a periodic calculation performed at a lower level of theory to model the crystalline environment. The GIPAW result is then corrected using a single molecule calculation performed at a higher level of theory. The success of the GIPAW + MC method in predicting a range of NMR parameters is a result of the highly local character of the tensors underlying the NMR observable. However, in applications involving strong intermolecular interactions we find that expanding the region treated at the higher level of theory more accurately captures local many-body contributions to the N15 NMR chemical shielding (CS) tensor. We propose alternative corrections to GIPAW which capture interactions between adjacent molecules at a higher level of theory using either fragment or cluster-based calculations. Benchmark calculations performed on N15 and C13 data sets show that these advanced GIPAW-corrected calculations improve the accuracy of chemical shielding tensor predictions relative to existing methods. Specifically, cluster-based N15 corrections show a 24% and 17% reduction in RMS error relative to GIPAW and GIPAW + MC calculations, respectively. Comparing the benchmark data sets using multiple computational models demonstrates that N15 CS tensor calculations are significantly more sensitive to intermolecular interactions relative to C13. However, fragment and cluster-based corrections that include direct hydrogen bond partners are sufficient for optimizing the accuracy of GIPAW-corrected methods. Finally, GIPAW-corrected methods are applied to the particularly challenging NMR spectral assignment of guanosine dihydrate which contains two guanosine molecules in the asymmetric unit.
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Guanosina , Espectroscopia de Ressonância Magnética/métodos , Ligação de HidrogênioRESUMO
The ability to theoretically predict accurate NMR chemical shifts in solids is increasingly important due to the role such shifts play in selecting among proposed model structures. Herein, two theoretical methods are evaluated for their ability to assign 15 N shifts from guanosine dihydrate to one of the two independent molecules present in the lattice. The NMR data consist of 15 N shift tensors from 10 resonances. Analysis using periodic boundary or fragment methods consider a benchmark dataset to estimate errors and predict uncertainties of 5.6 and 6.2â ppm, respectively. Despite this high accuracy, only one of the five sites were confidently assigned to a specific molecule of the asymmetric unit. This limitation is not due to negligible differences in experimental data, as most sites exhibit differences of >6.0â ppm between pairs of resonances representing a given position. Instead, the theoretical methods are insufficiently accurate to make assignments at most positions.
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Nuclear magnetic resonance (NMR) spectroscopy plays a crucial role in determining molecular structure for complex biological and pharmaceutical compounds. NMR investigations are increasingly reliant on computation for mapping spectral features to chemical structures. Here we benchmark the accuracy of fragment-based 51V chemical shielding tensor calculations using a training set comprised of 10 biologically and pharmaceutically relevant oxovanadium complexes. Using our self-consistent reproduction of the Madelung potential (SCRMP) electrostatic embedding model, we demonstrate comparable performance between fragment methods and computationally demanding cluster-based techniques. Specifically, fragment methods employing hybrid density functionals are capable of reproducing the experimental 51V isotropic chemical shifts with a training set rms error of ~9 âppm, representing a 20% improvement over traditional plane wave techniques. We provide training set-derived linear regression models for mapping the absolute shieldings obtained from computation to the experimentally determined chemical shifts using four common density functionals; PBE0, B3LYP, PBE, and BLYP. Finally, we establish the utility of fragment methods and the reported regression parameters examining four oxovanadium structures excluded from the training set including the tetracoordinate oxovanadium silicate [Formula: see text] , VO15NGlySalbz which contains redox-active ligands, and the solid-state form of the common 51V NMR reference compound VOCl3.
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Espectroscopia de Ressonância Magnética , Ligantes , Espectroscopia de Ressonância Magnética/métodos , Estrutura Molecular , Oxirredução , Eletricidade EstáticaRESUMO
BACKGROUND: People who inject drugs (PWID) are at increased risk for HIV acquisition and could benefit from antiretroviral pre-exposure prophylaxis (PrEP). However, PrEP has been underutilized in this population, and PrEP adherence intervention needs are understudied. METHODS: To inform PrEP intervention development, we reviewed evidence on antiretroviral therapy (ART) adherence among HIV-infected PWID. Guided by a behavioral model of healthcare utilization and using the PICOS framework, we conducted a systematic review in four electronic databases to identify original research studies of ART adherence in HIV-infected PWID in the United States and Canada between Jan 1, 2006-Dec 31, 2016. We synthesized and interpreted findings related to developing recommendations for PrEP adherence interventions for PWID. RESULTS: After excluding 618 duplicates and screening 1049 unique records, we retained 20 studies of PWID (mean n = 465) with adherence-related outcomes (via pharmacy records: n = 9; self-report: n = 8; biological markers: n = 5; electronic monitoring: n = 2). Predisposing factors (patient-level barriers to adherence) included younger age, female sex, and structural vulnerability (e.g., incarceration, homelessness). Enabling resources (i.e., facilitators) that could be leveraged or promoted by interventions included self-efficacy, substance use treatment, and high-quality patient-provider relationships. Competing needs that require specific intervention strategies or adaptations included markers of poor physical health, mental health comorbidities (e.g., depression), and engagement in transactional sex. CONCLUSIONS: HIV treatment adherence research carries important lessons for efforts to optimize PrEP adherence among PWID. Despite limitations, this systematic review suggests that strategies are needed to engage highly vulnerable and marginalized sub-groups of this underserved population (e.g., younger PWID, women who inject drugs) in PrEP adherence-related research and programming.
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Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Abuso de Substâncias por Via Intravenosa/epidemiologia , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Canadá/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , Profilaxia Pré-Exposição/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados Unidos/epidemiologiaRESUMO
The opioid receptors modulate a variety of biological functions, including pain, mood, and reward. As a result, opioid ligands are being explored as potential therapeutics for a variety of indications. Multifunctional opioid ligands, which act simultaneously at more than one type of opioid receptor, show promise for use in the treatment of addiction, pain, and other conditions. Previously, we reported the creation of bifunctional kappa opioid receptor (KOR) agonist/mu opioid receptor (MOR) partial agonist ligands from the classically delta opioid receptor (DOR) antagonist selective dimethyltyrosine-tetrahydroisoquinoline (Dmt-Tiq) scaffold through the addition of a 7-benzyl pendant on the tetrahydroisoquinoline ring. This study further explores the structure-activity relationships surrounding 7-position pendants on the Dmt-Tiq scaffold. Some analogues maintain a KOR agonist/MOR partial agonist profile, which is being explored in the development of a treatment for cocaine addiction. Others display a MOR agonist/DOR antagonist profile, which has potential to be used in the creation of a less addictive pain medication. Ultimately, we report the synthesis and in vitro evaluation of novel opioid ligands with a variety of multifunctional profiles.
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Analgésicos Opioides/metabolismo , Peptidomiméticos/química , Peptidomiméticos/farmacologia , Tetra-Hidroisoquinolinas/química , Tetra-Hidroisoquinolinas/farmacologia , Animais , Células CHO , Linhagem Celular , Cricetulus , Humanos , Dor/tratamento farmacológico , Dor/metabolismo , Manejo da Dor/métodos , Receptores Opioides/metabolismo , Relação Estrutura-AtividadeRESUMO
Standard nuclear magnetic resonance (NMR) spectroscopy experiments measure isotropic chemical shifts, but measuring the chemical shielding anisotropy (CSA) tensor can provide additional insights into solid state chemical structures. Interpreting the principal components of these tensors is facilitated by first-principles chemical shielding tensor predictions. Here, the ability to predict molecular crystal CSA tensor components for 13C and 15N nuclei with fragment-based electronic structure techniques is explored. Similar to what has been found previously for isotropic chemical shifts, the benchmarking demonstrates that fragment-based techniques can accurately reproduce CSA tensor components. The use of hybrid density functionals like PBE0 or B3LYP provide higher accuracy than generalized gradient approximation functionals like PBE. Unlike for planewave density functional techniques, hybrid density functionals can be employed routinely with modest computational cost in fragment approaches. Finally, good consistency between the regression parameters used to map either isotropic shieldings or CSA tensor components is demonstrated, providing further evidence for the quality of the models and highlighting that models trained for isotropic shifts can also be applied to CSA tensor components.
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Molecular crystals occur widely in pharmaceuticals, foods, explosives, organic semiconductors, and many other applications. Thanks to substantial progress in electronic structure modeling of molecular crystals, attention is now shifting from basic crystal structure prediction and lattice energy modeling toward the accurate prediction of experimentally observable properties at finite temperatures and pressures. This Account discusses how fragment-based electronic structure methods can be used to model a variety of experimentally relevant molecular crystal properties. First, it describes the coupling of fragment electronic structure models with quasi-harmonic techniques for modeling the thermal expansion of molecular crystals, and what effects this expansion has on thermochemical and mechanical properties. Excellent agreement with experiment is demonstrated for the molar volume, sublimation enthalpy, entropy, and free energy, and the bulk modulus of phase I carbon dioxide when large basis second-order Møller-Plesset perturbation theory (MP2) or coupled cluster theories (CCSD(T)) are used. In addition, physical insight is offered into how neglect of thermal expansion affects these properties. Zero-point vibrational motion leads to an appreciable expansion in the molar volume; in carbon dioxide, it accounts for around 30% of the overall volume expansion between the electronic structure energy minimum and the molar volume at the sublimation point. In addition, because thermal expansion typically weakens the intermolecular interactions, neglecting thermal expansion artificially stabilizes the solid and causes the sublimation enthalpy to be too large at higher temperatures. Thermal expansion also frequently weakens the lower-frequency lattice phonon modes; neglecting thermal expansion causes the entropy of sublimation to be overestimated. Interestingly, the sublimation free energy is less significantly affected by neglecting thermal expansion because the systematic errors in the enthalpy and entropy cancel somewhat. Second, because solid state nuclear magnetic resonance (NMR) plays an increasingly important role in molecular crystal studies, this Account discusses how fragment methods can be used to achieve higher-accuracy chemical shifts in molecular crystals. Whereas widely used plane wave density functional theory models are largely restricted to generalized gradient approximation (GGA) functionals like PBE in practice, fragment methods allow the routine use of hybrid density functionals with only modest increases in computational cost. In extensive molecular crystal benchmarks, hybrid functionals like PBE0 predict chemical shifts with 20-30% higher accuracy than GGAs, particularly for 1H, 13C, and 15N nuclei. Due to their higher sensitivity to polarization effects, 17O chemical shifts prove slightly harder to predict with fragment methods. Nevertheless, the fragment model results are still competitive with those from GIPAW. The improved accuracy achievable with fragment approaches and hybrid density functionals increases discrimination between different potential assignments of individual shifts or crystal structures, which is critical in NMR crystallography applications. This higher accuracy and greater discrimination are highlighted in application to the solid state NMR of different acetaminophen and testosterone crystal forms.
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Cristalografia/métodos , Espectroscopia de Ressonância Magnética/métodos , Termodinâmica , Acetaminofen/química , Modelos Químicos , Modelos Moleculares , Teoria Quântica , Temperatura , Testosterona/químicaRESUMO
NMR studies measuring chemical shift tensors are increasingly being employed to assign structure in difficult-to-crystallize solids. For small organic molecules, such studies usually focus on 13 C sites, but proteins and peptides are more commonly described using 15 N amide sites. An important and often neglected consideration when measuring shift tensors is the evaluation of their accuracy against benchmark standards, where available. Here we measure 15 N tensors in the dipeptide glycylglycine at natural abundance using the slow-spinning FIREMAT method with SPINAL-64 decoupling. The accuracy of these 15 N tensors is evaluated by comparing to benchmark single crystal NMR 15 N measurements and found to be statistically indistinguishable. These FIREMAT experimental results are further used to evaluate the accuracy of theoretical predictions of tensors from four different density functional theory (DFT) methods that include lattice effects. The best theoretical approach provides a root mean square (rms) difference of ±3.9â ppm and is obtained from a fragment-based method and the PBE0 density functional.
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Ressonância Magnética Nuclear Biomolecular , Peptídeos/química , Modelos Moleculares , Conformação Proteica , Teoria QuânticaRESUMO
The performance of fragment-based ab initio(1)H, (13)C, (15)N and (17)O chemical shift predictions is assessed against experimental NMR chemical shift data in four benchmark sets of molecular crystals. Employing a variety of commonly used density functionals (PBE0, B3LYP, TPSSh, OPBE, PBE, TPSS), we explore the relative performance of cluster, two-body fragment, and combined cluster/fragment models. The hybrid density functionals (PBE0, B3LYP and TPSSh) generally out-perform their generalized gradient approximation (GGA)-based counterparts. (1)H, (13)C, (15)N, and (17)O isotropic chemical shifts can be predicted with root-mean-square errors of 0.3, 1.5, 4.2, and 9.8 ppm, respectively, using a computationally inexpensive electrostatically embedded two-body PBE0 fragment model. Oxygen chemical shieldings prove particularly sensitive to local many-body effects, and using a combined cluster/fragment model instead of the simple two-body fragment model decreases the root-mean-square errors to 7.6 ppm. These fragment-based model errors compare favorably with GIPAW PBE ones of 0.4, 2.2, 5.4, and 7.2 ppm for the same (1)H, (13)C, (15)N, and (17)O test sets. Using these benchmark calculations, a set of recommended linear regression parameters for mapping between calculated chemical shieldings and observed chemical shifts are provided and their robustness assessed using statistical cross-validation. We demonstrate the utility of these approaches and the reported scaling parameters on applications to 9-tert-butyl anthracene, several histidine co-crystals, benzoic acid and the C-nitrosoarene SnCl2(CH3)2(NODMA)2.
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Ab initio chemical shielding calculations greatly facilitate the interpretation of nuclear magnetic resonance (NMR) chemical shifts in biological systems, but the large sizes of these systems requires approximations in the chemical models used to represent them. Achieving good convergence in the predicted chemical shieldings is necessary before one can unravel how other complex structural and dynamical factors affect the NMR measurements. Here, we investigate how to balance trade-offs between using a better basis set or a larger cluster model for predicting the chemical shieldings of the substrates in two representative examples of protein-substrate systems involving different domains in tryptophan synthase: the N-(4'-trifluoromethoxybenzoyl)-2-aminoethyl phosphate (F9) ligand which binds in the α active site, and the 2-aminophenol quinonoid intermediate formed in the ß active site. We first demonstrate that a chemically intuitive three-layer, locally dense basis model that uses a large basis on the substrate, a medium triple-zeta basis to describe its hydrogen-bonding partners and/or surrounding van der Waals cavity, and a crude basis set for more distant atoms provides chemical shieldings in good agreement with much more expensive large basis calculations. Second, long-range quantum mechanical interactions are important, and one can accurately estimate them as a small-basis correction to larger-basis calculations on a smaller cluster. The combination of these approaches enables one to perform density functional theory NMR chemical shift calculations in protein systems that are well-converged with respect to both basis set and cluster size.
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Ressonância Magnética Nuclear Biomolecular/métodos , Proteínas/química , Cristalografia , Modelos Químicos , Modelos MolecularesRESUMO
We assess the quality of fragment-based ab initio isotropic (13)C chemical shift predictions for a collection of 25 molecular crystals with eight different density functionals. We explore the relative performance of cluster, two-body fragment, combined cluster/fragment, and the planewave gauge-including projector augmented wave (GIPAW) models relative to experiment. When electrostatic embedding is employed to capture many-body polarization effects, the simple and computationally inexpensive two-body fragment model predicts both isotropic (13)C chemical shifts and the chemical shielding tensors as well as both cluster models and the GIPAW approach. Unlike the GIPAW approach, hybrid density functionals can be used readily in a fragment model, and all four hybrid functionals tested here (PBE0, B3LYP, B3PW91, and B97-2) predict chemical shifts in noticeably better agreement with experiment than the four generalized gradient approximation (GGA) functionals considered (PBE, OPBE, BLYP, and BP86). A set of recommended linear regression parameters for mapping between calculated chemical shieldings and observed chemical shifts are provided based on these benchmark calculations. Statistical cross-validation procedures are used to demonstrate the robustness of these fits.
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Controlling charge transfer at a molecular scale is critical for efficient light harvesting, energy conversion, and nanoelectronics. Dipole-polarization electrets, the electrostatic analogue of magnets, provide a means for "steering" electron transduction via the local electric fields generated by their permanent electric dipoles. Here, we describe the first demonstration of the utility of anthranilamides, moieties with ordered dipoles, for controlling intramolecular charge transfer. Donor-acceptor dyads, each containing a single anthranilamide moiety, distinctly rectify both the forward photoinduced electron transfer and the subsequent charge recombination. Changes in the observed charge-transfer kinetics as a function of media polarity were consistent with the anticipated effects of the anthranilamide molecular dipoles on the rectification. The regioselectivity of electron transfer and the molecular dynamics of the dyads further modulated the observed kinetics, particularly for charge recombination. These findings reveal the underlying complexity of dipole-induced effects on electron transfer and demonstrate unexplored paradigms for molecular rectifiers.
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ortoaminobenzoatos/química , Transporte de Elétrons , Elétrons , Cinética , Simulação de Dinâmica Molecular , Eletricidade Estática , EstereoisomerismoRESUMO
OBJECTIVE: To explore the association between human papillomavirus (HPV) vaccination and risk of coronavirus disease 2019 (COVID-19). Specifically, our study aimed to test the hypothesis that HPV vaccination may also induce trained immunity, which would potentially reduce the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and improve clinical outcomes. BACKGROUND: Several vaccines have been reported to trigger non-specific immune reactions that could offer protection from heterologous infections. A recent case report showed that verruca vulgaris regressed after COVID-19, suggesting a possible negative association between COVID-19 and HPV infection. METHODS: We enrolled 57,584 women with HPV vaccination and compared them with propensity score-matched controls who never received HPV vaccination in relation to the risk of COVID-19 incidence. Cox proportional hazard regression analysis was conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses stratified by age, race, comorbid asthma, and obesity were performed. RESULTS: The risk of COVID-19 incidence was significantly lower in those who had recently received the HPV vaccine (within 1 year after HPV vaccination, aHR: 0.818, 95% CI 0.764-0.876; within 1-2 years after HPV vaccination, aHR: 0.890, 95% CI 0.824-0.961). Several limitations were recognized in this study, including residual confounding, problems of misclassification due to the use of electronic health record data, and that we were unable to keep track of the patients' HPV infection status and the HPV antibody levels in those who had received the vaccine. CONCLUSIONS: Recent HPV vaccination was associated with a lower risk of incident COVID-19 and hospitalization. Based on the promising protective effect of HPV vaccine shown in this study, these findings should be replicated in an independent dataset. Further studies are needed to provide a better understanding of the underlying mechanisms and the differences in risks among 2-, 4-, or 9-valent HPV vaccine recipients.
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COVID-19 , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Humanos , Feminino , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/complicações , Papillomavirus Humano , Estudos de Coortes , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/complicações , SARS-CoV-2 , VacinaçãoRESUMO
Water-soluble deep cavitands with cationic functions at the lower rim can selectively bind iodide anions in purely aqueous solution. By pairing this lower rim recognition with an indicator dye that is bound in the host cavity, optical sensing of anions is possible. The selectivity for iodide is high enough that micromolar concentrations of iodide can be detected in the presence of molar chloride. Iodide binding at the "remote" lower rim causes a conformational change in the host, displacing the bound dye from the cavity and effecting a fluorescence response. The sensing is sensitive, selective, and works in complex environments, so will be important for optical anion detection in biorelevant media.
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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.