Distinguishing between COOH, COO- , and hydrogen disordered COOH sites in solids with 13 C chemical shift anisotropy and T1 measurements.

Since 1993, it has been known that 13 C chemical shift tensor (i.e., δ11 , δ22 , and δ33 ) provides information sufficient to distinguish between COOH and COO- sites. Herein, four previously unreported metrics are proposed for differentiating COOH/COO- moieties. A new relationship is also introduced that correlates the asymmetry (i.e., δ11 -δ22 ) of COOH sites to the proximity of hydrogen bond donating partners within 2.6 Å with high accuracy (±0.05 Å). Conversely, a limitation to all proposed metrics is that they fail to distinguish between COO- and hydrogen disordered COOH sites. To reconcile this omission, a new approach is proposed based on T1 measurements of both 1 H and 13 C. The 13 C T1 values are particularly sensitive with the T1 for hydrogen disordered COOH moieties found to be nearly six times smaller than T1 's from COO- sites.

Synergistic Steric and Electronic Effects on the Photoredox Catalysis by a Multivariate Library of Titania Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) that display photoredox activity are attractive materials for sustainable photocatalysis. The ability to tune both their pore sizes and electronic structures based solely on the choice of the building blocks makes them amenable for systematic studies based on physical organic and reticular chemistry principles with high degrees of synthetic control. Here, we present a library of eleven isoreticular and multivariate (MTV) photoredox-active MOFs, UCFMOF-n, and UCFMTV-n-x% with a formula Ti6O9[links]3, where the links are linear oligo-p-arylene dicarboxylates with n number of p-arylene rings and x mol% of multivariate links containing electron-donating groups (EDGs). The average and local structures of UCFMOFs were elucidated from advanced powder X-ray diffraction (XRD) and total scattering tools, consisting of parallel arrangements of one-dimensional (1D) [Ti6O9(CO2)6]∞ nanowires connected through the oligo-arylene links with the topology of the edge-2-transitive rod-packed hex net. Preparation of an MTV library of UCFMOFs with varying link sizes and amine EDG functionalization enabled us to study both their steric (pore size) and electronic (highest occupied molecular orbital-lowest unoccupied molecular orbital, HOMO-LUMO, gap) effects on the substrate adsorption and photoredox transformation of benzyl alcohol. The observed relationship between the substrate uptake and reaction kinetics with the molecular traits of the links indicates that longer links, as well as increased EDG functionalization, exhibit impressive photocatalytic rates, outperforming MIL-125 by almost 20-fold. Our studies relating photocatalytic activity with pore size and electronic functionalization demonstrate how these are important parameters to consider when designing new MOF photocatalysts.

A new depsidone from the neotricone-rich chemotype of the lichenised fungus Usnea fulvoreagens.

Individuals of Usnea fulvoreagens (Parmeliaceae, lichenised Ascomycota), a shrubby corticolous species that is widespread in Europe, East Asia and North America, produce medullary lichen acids in several distinct chemotypic patterns. One such chemotype reportedly contains an unidentified substance as the major secondary metabolite. We isolated this compound from Californian specimens of U. fulvoreagens and identified it as the rare depsidone neotricone. A co-occurring compound, conneotricone, was identified as 4,10-dihydroxy-5-(hydroxymethyl)-8-methyl-3,7-dioxo-1,3-dihydro-7H-isobenzofuro[4,5-b][1,4]benzodioxepine-11-carboxylic acid by NMR and HPLC-UV-MSn comparison with the material synthesised from salazinic acid.

Benchmark accuracy of predicted NMR observables for quadrupolar 14 N and 17 O nuclei in molecular crystals.

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.

Improving the accuracy of GIPAW chemical shielding calculations with cluster and fragment corrections.

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.

Rapid, Quantitative Nuclear Magnetic Resonance Test for Oxygen-17 Enrichment in Water.

Nuclear magnetic resonance (NMR) studies involving 17O are increasingly important in molecular biology, material science, and other disciplines. A large number of these studies employ H217O as a source of 17O, and this reliance can be limiting because the high cost of H217O. To overcome this constraint, a recent study proposed a distillation scheme capable of producing significant quantities of H217O at a low cost. Although this method is reported to be effective, the reactions proposed to quantify percent of 17O enrichment are either time intensive or have a risk of errors due to the isotope effect. Here, an alternative reaction scheme is described to measure 17O water that ultimately creates methyl benzoate as the sole 17O-containing product. The proposed reaction is completed in a matter of minutes at room temperature, produces only one 17O product, and requires no clean-up step. The large isotope shift observed in solution NMR between the 13C═16O and 13C═17O resonances allows for integration of the individual peaks. This 13C NMR analysis is found to be highly accurate over a wide enrichment range and is accessible to most NMR spectroscopists.

Proline Isomerization as a Key Determinant for Hsp90-Toxin Interactions.

The A chains of ADP-ribosylating toxins exploit Hsp90 for translocation into the host cytosol. Here, we hypothesize that cis proline residues play a key role in toxin recognition by Hsp90. Our model is largely derived from studies on the unusual interplay between Hsp90 and the catalytic A1 subunit of cholera toxin (CTA1), including the recent identification of an RPPDEI-like binding motif for Hsp90 in CTA1 and several other bacterial toxins. Cis/trans proline isomerization is known to influence protein-protein interactions and protein structure/function, but it has not yet been proposed to affect Hsp90-toxin interactions. Our model thus provides a new framework to understand the molecular basis for Hsp90 chaperone function and Hsp90-driven toxin translocation.

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.

Modeling Small Structural and Environmental Differences in Solids with 15 N†NMR Chemical Shift Tensors.

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 6.2 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 >6.0 ppm between pairs of resonances representing a given position. Instead, the theoretical methods are insufficiently accurate to make assignments at most positions.

NMR structural characterization from one-bond 13 C13 C couplings: Complete assignment of a hydrogen-poor depsidone.

The connectivity, conformation, tautomeric form, and dynamics of a new depsidone (perisalazinic acid) were characterized using one-bond 13 C13 C NMR scalar couplings (1 JCC ) obtained from the INADEQUATE experiment. Characterization of perisalazinic acid using more conventional NMR techniques is problematic due to the extremely limited number of CH protons present. In the present study, 81 candidate structures were considered and a best fit structure was selected by comparing computed 1 JCC values for each candidate to 15 experimental values. Of the six flexible moieties in perisalazinic acid, three are adequately represented by a single orientation stabilized by intramolecular hydrogen bonding. The three remaining groups are present as mixtures of conformers with two sites consisting of a pair of conformations and another disordered over six orientations. This study demonstrates the feasibility of complete three-dimensional structural characterization of an unknown using only theoretical and experimental 1 JCC values.

"One-Shot" Measurement of Residual Chemical Shift Anisotropy Using Poly-γ-benzyl-l-glutamate as an Alignment Medium.

A method for the measurement of residual chemical shift anisotropy in one experiment using a biphasic isotropic/anisotropic lyotropic liquid crystalline medium based on poly-γ-benzyl-l-glutamate as the alignment medium is presented. This approach is demonstrated on the model compound strychnine and neotricone, a depsidone natural product with a questionable structural assignment based on comparison with the closely related excelsione and in-depth density functional theory calculations.

Characterization of a Bio-sourced, Fluorescent, Ratiometric pH Indicator with Alkaline pKa.

Utilizing organisms as sources of fluorophores relieves the demand for petroleum feedstock in organic synthesis of fluorescent products, and endophytic fungi provide a promising vein for natural fluorescent products. We report the characterization of a pH-responsive fluorophore from an endophytic fungus isolated from sand pine. The endogenous fluorescence of the live organism was measured using fluorescence microscopy. Computational interpretation of the spectra was accomplished with time-dependent density functional theory methods. The combined use of experimental and theoretically predicted spectra revealed the pH equilibria and photoexcited tautomerization of the natural product, 5-methylmellein. This product shows promise both as a stand-alone pH-indicating fluorophore, with alkaline pKa , and as "green" feedstock for synthesis of custom fluorophores.

Chemical Shift Tensors of Cimetidine Form A Modeled with Density Functional Theory Calculations: Implications for NMR Crystallography.

The principal components of the 13C chemical shift tensors for the ten crystallographically distinct carbon atoms of the active pharmaceutical ingredient cimetidine Form A have been measured using the FIREMAT technique. Density functional theory (DFT) calculations of 13C and 15N magnetic shielding tensors are used to assign the 13C and 15N peaks. DFT calculations were performed on cimetidine and a training set of organic crystals using both plane-wave and cluster-based approaches. The former set of calculations allowed several structural refinement strategies to be employed, including calculations utilizing a dispersion-corrected force field that was parametrized using 13C and 15N magnetic shielding tensors. The latter set of calculations featured the use of resource-intensive hybrid-DFT methods for the calculation of magnetic shielding tensors. Calculations on structures refined using the new force-field correction result in improved values of 15N magnetic shielding tensors (as gauged by agreement with experimental chemical shift tensors), although little improvement is seen in the prediction of 13C shielding tensors. Calculations of 13C and 15N magnetic shielding tensors using hybrid functionals show better agreement with experimental values in comparison to those using GGA functionals, independent of the method of structural refinement; the shielding of carbon atoms bonded to nitrogen are especially improved using hybrid DFT methods.

Solid-State 13 C†NMR Evidence for Long Multicenter Intradimer Bonding in Zwitterion-like Structures.

The principal values of the 13 C chemical shift tensor for the ß and δ polymorphs of π-[TTF⋅⋅⋅TCNE] (TTF=tetrathiafulvalene; TCNE=tetracyanoethylene) have been analyzed to understand the abnormally long intra-dimer bonding of singlet π-[TTFδ+ ⋅⋅⋅TCNEδ- ]. These structures possess 12 intradimer contacts <3.40 Å, with the shortest intra π-[TTF⋅⋅⋅TCNE] separations involving 2-center (2c) C-S and 3c C-C-C orbital overlap contributions between the [TTF]δ+ and [TCNE]δ- . This solid-state NMR study compares the [TTF⋅⋅⋅TCNE] 13 C tensor data against previously reported π-[TTF]2 2+ and π-[TCNE]2 2- homo-dimers to determine how the tensor principal values change as a function of electronic structure for both TTF and TCNE moieties. In the ß and δ phases of [TTF⋅⋅⋅TCNE], the TCNE ethylenic 13 C shift tensors predict TCNE oxidation states of -0.46 and -0.73, respectively. The TTF sites are less similar to benchmark 13 C data with the ß-phase differing primarily in the ethylenic π-electrons. The δ form differs significantly from the homo-dimer data at all principal values at both the ethylenic and CH sites, indicating changes to both the π-electrons and σ-bonds. In both hetero-dimer phases, the NMR changes supports long bond formation at nitrile and CH sites not observed in homo-dimers.

Solid State Multicolor Emission in Substitutional Solid Solutions of Metal-Organic Frameworks.

Preparing crystalline materials that produce tunable organic-based multicolor emission is a challenge due to the inherent inability to control the packing of organic molecules in the solid state. Utilizing multivariate, high-symmetry metal-organic frameworks, MOFs, as matrices for organic-based substitutional solid solutions allows for the incorporation of multiple fluorophores with different emission profiles into a single material. By combining nonfluorescent links with dilute mixtures of red, green, and blue fluorescent links, we prepared zirconia-type MOFs and found that the bulk materials exhibit features of solution-like fluorescence. Our study found that MOFs with a fluorophore link concentration of around 1 mol % exhibit fluorescence with decreased inner filtering, demonstrated by changes in spectral profiles, increased quantum yields, and lifetime dynamics expected for excited-state proton-transfer emitters. Our findings enabled us to prepare organic-based substitutional solid solutions with tunable chromaticity regulated only by the initial amounts of fluorophores. These materials emit multicolor and white light with high quantum yields (∼2-14%), high color-rendering indices (>93), long shelf life, and superb hydrolytic stability at ambient conditions.

TensorView: A software tool for displaying NMR tensors.

The representation of nuclear magnetic resonance (NMR) tensors as surfaces on three-dimensional molecular models is an information-rich presentation that highlights the geometric relationship between tensor principal components and the underlying molecular and electronic structure. Here, we describe a new computational tool, TensorView, for depicting NMR tensors on the molecular framework. This package makes use of the graphical interface and built-in molecular display functionality present within the Mathematica programming environment and is robust for displaying tensor properties from a broad range of commercial and user-specific computational chemistry packages. Two mathematical forms for representing tensor interaction surfaces are presented, the popular ellipsoidal construct and the more technically correct "ovaloid" form. Examples are provided for chemical shielding and shift tensors, dipole-dipole and quadrupolar couplings, and atomic anisotropic displacement parameters (thermal ellipsoids) derived from NMR crystallography.

Carbon Nitride Dots: A Selective Bioimaging Nanomaterial.

In contrast to the recent immense attention in carbon nitride quantum dots (CNQDs) as a heteroatom-doped carbon quantum dot (CQD), their biomedical applications have not been thoroughly investigated. Targeted cancer therapy is a prominently researched area in the biomedical field. Here, the ability of CNQDs as a selective bioimaging nanomaterial was investigated to assist targeted cancer therapy. CNQDs were first synthesized using four different precursor sets involving urea derivatives, and the characteristics were compared to select the best candidate material for bioapplications. Characterization techniques such as UV-vis, luminescence, X-ray photoelectron spectroscopy, nuclear magnetic resonance spectroscopy, and transmission electron microscopy were used. These CNQDs were analyzed in in vitro studies of bioimaging and labeling using pediatric glioma cells (SJGBM2) for possible selective biolabeling and nanodistribution inside the cell membrane. The in vitro cellular studies were conducted under long-wavelength emission without the interference of blue autofluorescence. Thus, excitation-dependent emission of CNQDs was proved to be advantageous. Importantly, CNQDs selectively entered SJGBM2 tumor cells, while it did not disperse into normal human embryonic kidney cells (HEK293). The distribution studies in the cell cytoplasm indicated that CNQDs dispersed into lysosomes within approximately 6 h after the incubation. The CNQDs exhibited great potential as a possible nanomaterial in selective bioimaging and drug delivery for targeted cancer therapy.

A Solvent-Free Approach for Converting Cellulose Waste into Volatile Organic Compounds with Endophytic Fungi.

Simple sugars produced from a solvent-free mechanocatalytic degradation of cellulose were evaluated for suitability as a growth medium carbon source for fungi that produce volatile organic compounds. An endophytic Hypoxylon sp. (CI-4) known to produce volatiles having potential value as fuels was initially evaluated. The growth was obtained on a medium containing the degraded cellulose as the sole carbon source, and the volatile compounds produced were largely the same as those produced from a conventional dextrose/starch diet. A second Hypoxylon sp. (BS15) was also characterized and shown to be phylogenetically divergent from any other named species. The degraded cellulose medium supported the growth of BS15, and approximately the same quantity of the volatile compounds was produced as from conventional diets. Although the major products from BS15 grown on the degraded cellulose were identical to those from dextrose, the minor products differed. Neither CI-4 or BS15 exhibited growth on cellulose that had not been degraded. The extraction of volatiles from the growth media was achieved using solid-phase extraction in order to reduce the solvent waste and more efficiently retain compounds having low vapor pressures. A comparison to more conventional liquid⁻liquid extraction demonstrated that, for CI-4, both methods gave similar results. The solid-phase extraction of BS15 retained a significantly larger variety of the volatile compounds than did the liquid⁻liquid extraction. These advances position the coupling of solvent-free cellulose conversion and endophyte metabolism as a viable strategy for the production of important hydrocarbons.