Structure Determination of Biogenic Crystals Directly from 3D Electron Diffraction Data.

Highly reflective assemblies of purine, pteridine, and flavin crystals are used in the coloration and visual systems of many different animals. However, structure determination of biogenic crystals by single-crystal XRD is challenging due to the submicrometer size and beam sensitivity of the crystals, and powder XRD is inhibited due to the small volumes of powders, crystalline impurity phases, and significant preferred orientation. Consequently, the crystal structures of many biogenic materials remain unknown. Herein, we demonstrate that the 3D electron diffraction (3D ED) technique provides a powerful alternative approach, reporting the successful structure determination of biogenic guanine crystals (from spider integument, fish scales, and scallop eyes) from 3D ED data confirmed by analysis of powder XRD data. The results show that all biogenic guanine crystals studied are the previously known ß-polymorph. This study highlights the considerable potential of 3D ED for elucidating the structures of biogenic molecular crystals in the nanometer-to-micrometer size range. This opens up an important opportunity in the development of organic biomineralization, for which structural knowledge is critical for understanding the optical functions of biogenic materials and their possible applications as sustainable, biocompatible optical materials.

Exploiting solid-state dynamic nuclear polarization NMR spectroscopy to establish the spatial distribution of polymorphic phases in a solid material.

Solid-state DNP NMR can enhance the ability to detect minor amounts of solid phases within heterogenous materials. Here we demonstrate that NMR contrast based on the transport of DNP-enhanced polarization can be exploited in the challenging case of early detection of a small amount of a minor polymorphic phase within a major polymorph, and we show that this approach can yield quantitative information on the spatial distribution of the two polymorphs. We focus on the detection of a minor amount (<4%) of polymorph III of m-aminobenzoic acid within a powder sample of polymorph I at natural isotopic abundance. Based on proposed models of the spatial distribution of the two polymorphs, simulations of 1H spin diffusion allow NMR data to be calculated for each model as a function of particle size and the relative amounts of the polymorphs. A comparison between simulated and experimental NMR data allows the model(s) best representing the spatial distribution of the polymorphs in the system to be established.

Unraveling the Complex Solid-State Phase Transition Behavior of 1-Iodoadamantane, a Material for Which Ostensibly Identical Crystals Undergo Different Transformation Pathways.

Phase transitions in crystalline molecular solids have important implications in the fundamental understanding of materials properties and in the development of materials applications. Herein, we report the solid-state phase transition behavior of 1-iodoadamantane (1-IA) investigated using a multi-technique strategy [synchrotron powder X-ray diffraction (XRD), single-crystal XRD, solid-state NMR, and differential scanning calorimetry (DSC)], which reveals complex phase transition behavior on cooling from ambient temperature to ca. 123 K and on subsequent heating to the melting temperature (348 K). Starting from the known phase of 1-IA at ambient temperature (phase A), three low-temperature phases are identified (phases B, C, and D); the crystal structures of phases B and C are reported, together with a re-determination of the structure of phase A. Remarkably, single-crystal XRD shows that some individual crystals of phase A transform to phase B, while other crystals of phase A transform instead to phase C. Results (from powder XRD and DSC) on cooling a powder sample of phase A are fully consistent with this behavior while also revealing an additional transformation pathway from phase A to phase D. Thus, on cooling, a powder sample of phase A transforms partially to phase C (at 229 K), partially to phase D (at 226 K) and partially to phase B (at 211 K). During the cooling process, each of the phases B, C, and D is formed directly from phase A, and no transformations are observed between phases B, C, and D. On heating the resulting triphasic powder sample of phases B, C, and D from 123 K, phase B transforms to phase D (at 211 K), followed by the transformation of phase D to phase C (at 255 K), and finally, phase C transforms to phase A (at 284 K). From these observations, it is apparent that different crystals of phase A, which are ostensibly identical at the level of information revealed by XRD, must actually differ in other aspects that significantly influence their low-temperature phase transition pathways. This unusual behavior will stimulate future studies to gain deeper insights into the specific properties that control the phase transition pathways in individual crystals of this material.

Boron Nitride-Doped Polyphenylenic Organogels.

Herein, we describe the synthesis of the first boron nitride-doped polyphenylenic material obtained through a [4 + 2] cycloaddition reaction between a triethynyl borazine unit and a biscyclopentadienone derivative, which undergoes organogel formation in chlorinated solvents (the critical jellification concentration is 4% w/w in CHCl3). The polymer has been characterized extensively by Fourier-transform infrared spectroscopy, solid-state 13C NMR, solid-state 11B NMR, and by comparison with the isolated monomeric unit. Furthermore, the polymer gels formed in chlorinated solvents have been thoroughly characterized and studied, showing rheological properties comparable to those of polyacrylamide gels with a low crosslinker percentage. Given the thermal and chemical stability, the material was studied as a potential support for solid-state electrolytes. showing properties comparable to those of polyethylene glycol-based electrolytes, thus presenting great potential for the application of this new class of material in lithium-ion batteries.

A structure determination protocol based on combined analysis of 3D-ED data, powder XRD data, solid-state NMR data and DFT-D calculations reveals the structure of a new polymorph of l-tyrosine.

We report the crystal structure of a new polymorph of l-tyrosine (denoted the ß polymorph), prepared by crystallization from the gas phase following vacuum sublimation. Structure determination was carried out by combined analysis of three-dimensional electron diffraction (3D-ED) data and powder X-ray diffraction (XRD) data. Specifically, 3D-ED data were required for reliable unit cell determination and space group assignment, with structure solution carried out independently from both 3D-ED data and powder XRD data, using the direct-space strategy for structure solution implemented using a genetic algorithm. Structure refinement was carried out both from powder XRD data, using the Rietveld profile refinement technique, and from 3D-ED data. The final refined structure was validated both by periodic DFT-D calculations, which confirm that the structure corresponds to an energy minimum on the energy landscape, and by the fact that the values of isotropic 13C NMR chemical shifts calculated for the crystal structure using DFT-D methodology are in good agreement with the experimental high-resolution solid-state 13C NMR spectrum. Based on DFT-D calculations using the PBE0-MBD method, the ß polymorph is meta-stable with respect to the previously reported crystal structure of l-tyrosine (now denoted the α polymorph). Crystal structure prediction calculations using the AIRSS approach suggest that there are three other plausible crystalline polymorphs of l-tyrosine, with higher energy than the α and ß polymorphs.

Biogenic Guanine Crystals Are Solid Solutions of Guanine and Other Purine Metabolites.

Highly reflective crystals of the nucleotide base guanine are widely distributed in animal coloration and visual systems. Organisms precisely control the morphology and organization of the crystals to optimize different optical effects, but little is known about how this is achieved. Here we examine a fundamental question that has remained unanswered after over 100 years of research on guanine: what are the crystals made of? Using solution-state and solid-state chemical techniques coupled with structural analysis by powder XRD and solid-state NMR, we compare the purine compositions and the structures of seven biogenic guanine crystals with different crystal morphologies, testing the hypothesis that intracrystalline dopants influence the crystal shape. We find that biogenic "guanine" crystals are not pure crystals but molecular alloys (aka solid solutions and mixed crystals) of guanine, hypoxanthine, and sometimes xanthine. Guanine host crystals occlude homogeneous mixtures of other purines, sometimes in remarkably large amounts (up to 20% of hypoxanthine), without significantly altering the crystal structure of the guanine host. We find no correlation between the biogenic crystal morphology and dopant content and conclude that dopants do not dictate the crystal morphology of the guanine host. The ability of guanine crystals to host other molecules enables animals to build physiologically "cheaper" crystals from mixtures of metabolically available purines, without impeding optical functionality. The exceptional levels of doping in biogenic guanine offer inspiration for the design of mixed molecular crystals that incorporate multiple functionalities in a single material.

Solid-State Structural Properties of Alloxazine Determined from Powder XRD Data in Conjunction with DFT-D Calculations and Solid-State NMR Spectroscopy: Unraveling the Tautomeric Identity and Pathways for Tautomeric Interconversion.

We report the solid-state structural properties of alloxazine, a tricyclic ring system found in many biologically important molecules, with structure determination carried out directly from powder X-ray diffraction (XRD) data. As the crystal structures containing the alloxazine and isoalloxazine tautomers both give a high-quality fit to the powder XRD data in Rietveld refinement, other techniques are required to establish the tautomeric form in the solid state. In particular, high-resolution solid-state 15N NMR data support the presence of the alloxazine tautomer, based on comparison between isotropic chemical shifts in the experimental 15N NMR spectrum and the corresponding values calculated for the crystal structures containing the alloxazine and isoalloxazine tautomers. Furthermore, periodic DFT-D calculations at the PBE0-MBD level indicate that the crystal structure containing the alloxazine tautomer has significantly lower energy. We also report computational investigations of the interconversion between the tautomeric forms in the crystal structure via proton transfer along two intermolecular N-H···N hydrogen bonds; DFT-D calculations at the PBE0-MBD level indicate that the tautomeric interconversion is associated with a lower energy transition state for a mechanism involving concerted (rather than sequential) proton transfer along the two hydrogen bonds. However, based on the relative energies of the crystal structures containing the alloxazine and isoalloxazine tautomers, it is estimated that under conditions of thermal equilibrium at ambient temperature, more than 99.9% of the molecules in the crystal structure will exist as the alloxazine tautomer.

Direct-Space Structure Determination of Covalent Organic Frameworks from 3D Electron Diffraction Data.

Structure determination of covalent organic frameworks (COFs) with atomic precision is a bottleneck that hinders the development of COF chemistry. Although three-dimensional electron diffraction (3D-ED) data has been used to solve structures of sub-micrometer-sized COFs, successful structure solution is not guaranteed as the data resolution is usually low. We demonstrate that the direct-space strategy for structure solution, implemented using a genetic algorithm (GA), is a successful approach for structure determination of COF-300 from 3D-ED data. Structural models with different geometric constraints were considered in the GA calculations, with successful structure solution achieved from room-temperature 3D-ED data with a resolution as low as ca. 3.78 Å. The generality of this strategy was further verified for different phases of COF-300. This study demonstrates a viable strategy for structure solution of COF materials from 3D-ED data of limited resolution, which may facilitate the discovery of new COF materials in the future.

Boron-Nitrogen-Doped Nanographenes: A Synthetic Tale from Borazine Precursors.

In this work, a comprehensive account of the authors' synthetic efforts to prepare borazino-doped hexabenzocoronenes by using the Friedel-Crafts-type electrophilic aromatic substitution is reported. Hexafluoro-functionalized aryl borazines, bearing an ortho fluoride leaving group on each of the N- and B-aryl rings, was shown to lead to cascade-type electrophilic aromatic substitution events in the stepwise C-C bond formation, giving higher yields of borazinocoronenes than those obtained with borazine precursors bearing fluoride leaving groups at the ortho positions of the B-aryl substituents. By using this pathway, an unprecedented boroxadizine-doped PAH featuring a gulf-type periphery could be isolated, and its structure proven by single-crystal X-ray diffraction analysis. Mechanistic studies on the stepwise Friedel-Crafts-type cyclization suggest that the mechanism of the planarization reaction proceeds through extension of the π system. To appraise the doping effect of the boroxadizine unit on the optoelectronic properties of topology-equivalent molecular graphenes, the all-carbon and pyrylium PAH analogues, all featuring a gulf-type periphery, were also prepared. As already shown for the borazino-doped hexabenzocoronene, the replacement of the central benzene ring by its B3 N2 O congener widens the HOMO-LUMO gap and dramatically enhances the fluorescence quantum yield.

Exploiting in situ NMR to monitor the formation of a metal-organic framework.

The formation processes of metal-organic frameworks are becoming more widely researched using in situ techniques, although there remains a scarcity of NMR studies in this field. In this work, the synthesis of framework MFM-500(Ni) has been investigated using an in situ NMR strategy that provides information on the time-evolution of the reaction and crystallization process. In our in situ NMR study of MFM-500(Ni) formation, liquid-phase 1H NMR data recorded as a function of time at fixed temperatures (between 60 and 100 °C) afford qualitative information on the solution-phase processes and quantitative information on the kinetics of crystallization, allowing the activation energies for nucleation (61.4 ± 9.7 kJ mol-1) and growth (72.9 ± 8.6 kJ mol-1) to be determined. Ex situ small-angle X-ray scattering studies (at 80 °C) provide complementary nanoscale information on the rapid self-assembly prior to MOF crystallization and in situ powder X-ray diffraction confirms that the only crystalline phase present during the reaction (at 90 °C) is phase-pure MFM-500(Ni). This work demonstrates that in situ NMR experiments can shed new light on MOF synthesis, opening up the technique to provide better understanding of how MOFs are formed.

Rationalization of the X-ray photoelectron spectroscopy of aluminium phosphates synthesized from different precursors.

The aim of this paper is to clarify the assignments of X-ray photoelectron spectra of aluminium phosphate materials prepared from the reaction of phosphoric acid with three different aluminium precursors [Al(OH)3, Al(NO3)3 and AlCl3] at different annealing temperatures. The materials prepared have been studied by X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (XRD), infrared spectroscopy and high-resolution solid-state 31P NMR spectroscopy. A progressive polymerization from orthophosphate to metaphosphates is observed by XRD, ATR-FTIR and solid state 31P NMR, and on this basis the oxygen states observed in the XP spectra at 532.3 eV and 533.7 eV are assigned to P-O-Al and P-O-P environments, respectively. The presence of cyclic polyphosphates at the surface of the samples is also evident.

Polymorphism of l-Tryptophan.

A new polymorph of l-tryptophan was prepared through crystallization from the gas phase, with structure determination carried out directly from powder XRD data augmented by periodic DFT-D calculations. The new polymorph (denoted ß) and the previously reported polymorph (denoted α) are both based on alternating hydrophilic and hydrophobic layers, but with substantially different hydrogen-bonding arrangements. The ß polymorph exhibits the energetically favourable l2-l2 hydrogen-bonding arrangement, which is unprecedented for amino acids with aromatic side chains. The specific molecular conformations adopted in the ß polymorph facilitate this hydrogen-bonding scheme while avoiding steric conflict of the side chains.

A Strategy for Probing the Evolution of Crystallization Processes by Low-Temperature Solid-State NMR and Dynamic Nuclear Polarization.

Crystallization plays an important role in many areas, and to derive a fundamental understanding of crystallization processes, it is essential to understand the sequence of solid phases produced as a function of time. Here, we introduce a new NMR strategy for studying the time evolution of crystallization processes, in which the crystallizing system is quenched rapidly to low temperature at specific time points during crystallization. The crystallized phase present within the resultant "frozen solution" may be investigated in detail using a range of sophisticated NMR techniques. The low temperatures involved allow dynamic nuclear polarization (DNP) to be exploited to enhance the signal intensity in the solid-state NMR measurements, which is advantageous for detection and structural characterization of transient forms that are present only in small quantities. This work opens up the prospect of studying the very early stages of crystallization, at which the amount of solid phase present is intrinsically low.

Exploiting in-situ solid-state NMR spectroscopy to probe the early stages of hydration of calcium aluminate cement.

We report a high-field in-situ solid-state NMR study of the hydration of CaAl2O4 (the most important hydraulic phase in calcium aluminate cement), based on time-resolved measurements of solid-state 27Al NMR spectra during the early stages of the reaction. A variant of the CLASSIC NMR methodology, involving alternate recording of direct-excitation and MQMAS 27Al NMR spectra, was used to monitor the 27Al species present in both the solid and liquid phases as a function of time. Our results provide quantitative information on the changes in the relative amounts of 27Al sites with tetrahedral coordination (the anhydrous reactant phase) and octahedral coordination (the hydrated product phases) as a function of time, and reveal significantly different kinetic and mechanistic behaviour of the hydration reaction at the different temperatures (20 °C and 60 °C) studied.

Establishing the Transitory Existence of Amorphous Phases in Crystallization Pathways by the CLASSIC NMR Technique.

With the growing realization that crystallization processes may evolve through a sequence of different solid forms, including amorphous precursor phases, the development of suitable in-situ experimental probes is essential for comprehensively mapping the time-evolution of such processes. Here we demonstrate that the CLASSIC NMR (Combined Liquid- And Solid-State In-situ Crystallization NMR) strategy is a powerful technique for revealing the transitory existence of amorphous phases during crystallization processes, applying this technique to study crystallization of dl-menthol and l-menthol from their molten liquid phases. The CLASSIC NMR results provide direct insights into the conditions (including the specific time period) under which the molten liquid phase, transitory amorphous phases and final crystalline phases exist during these crystallization processes.

Polymorphic phase transformations of 3-chloro-trans-cinnamic acid and its solid solution with 3-bromo-trans-cinnamic acid.

We have investigated the polymorphic phase transformations above ambient temperature for 3-chloro-trans-cinnamic acid (3-ClCA, C9H7ClO2) and a solid solution of 3-ClCA and 3-bromo-trans-cinnamic acid (3-BrCA, C9H7BrO2). At 413 K, the γ polymorph of 3-ClCA transforms to the ß polymorph. Interestingly, the structure of the ß polymorph of 3-ClCA obtained in this transformation is different from the structure of the ß polymorph of 3-BrCA obtained in the corresponding polymorphic transformation from the γ polymorph of 3-BrCA, even though the γ polymorphs of 3-ClCA and 3-BrCA are isostructural. We also report a high-temperature phase transformation from a γ-type structure to a ß-type structure for a solid solution of 3-ClCA and 3-BrCA (with a molar ratio close to 1:1). The γ polymorph of the solid solution is isostructural with the γ polymorphs of pure 3-ClCA and pure 3-BrCA, while the ß-type structure produced in the phase transformation is structurally similar to the ß polymorph of pure 3-BrCA.

Insights into the Crystallization and Structural Evolution of Glycine Dihydrate by In†Situ Solid-State NMR Spectroscopy.

In situ solid-state NMR spectroscopy is exploited to monitor the structural evolution of a glycine/water glass phase formed on flash cooling an aqueous solution of glycine, with a range of modern solid-state NMR methods applied to elucidate structural properties of the solid phases present. The glycine/water glass is shown to crystallize into an intermediate phase, which then transforms to the ß polymorph of glycine. Our in situ NMR results fully corroborate the identity of the intermediate crystalline phase as glycine dihydrate, which was first proposed only very recently.

Ab initio random structure searching of organic molecular solids: assessment and validation against experimental data.

This paper explores the capability of using the DFT-D ab initio random structure searching (AIRSS) method to generate crystal structures of organic molecular materials, focusing on a system (m-aminobenzoic acid; m-ABA) that is known from experimental studies to exhibit abundant polymorphism. Within the structural constraints selected for the AIRSS calculations (specifically, centrosymmetric structures with Z = 4 for zwitterionic m-ABA molecules), the method is shown to successfully generate the two known polymorphs of m-ABA (form III and form IV) that have these structural features. We highlight various issues that are encountered in comparing crystal structures generated by AIRSS to experimental powder X-ray diffraction (XRD) data and solid-state magic-angle spinning (MAS) NMR data, demonstrating successful fitting for some of the lowest energy structures from the AIRSS calculations against experimental low-temperature powder XRD data for known polymorphs of m-ABA, and showing that comparison of computed and experimental solid-state NMR parameters allows different hydrogen-bonding motifs to be discriminated.

Assessing the Detection Limit of a Minority Solid-State Form of a Pharmaceutical by 1H Double-Quantum Magic-Angle Spinning Nuclear Magnetic Resonance Spectroscopy.

The lower detection limit for 2 distinct crystalline phases by 1H magic-angle spinning (MAS) solid-state nuclear magnetic resonance (NMR) is investigated for a minority amount of cimetidine (anhydrous polymorph A) in a physical mixture with the anhydrous HCl salt of cimetidine. Specifically, 2-dimensional 1H double-quantum (DQ) MAS NMR spectra of polymorph A and the anhydrous HCl salt constitute fingerprints for the presence of each of these solid forms. For solid-state NMR data recorded at a 1H Larmor frequency of 850 MHz and a MAS frequency of 30 kHz on ∼10 mg of sample, it is shown that, by following the pair of cross-peaks at a 1H DQ frequency of 7.4 + 11.6 = 19.0 ppm that are unique to polymorph A, the level of detection for polymorph A in a physical mixture with the anhydrous HCl salt is a concentration of 1% w/w.

Determination of a complex crystal structure in the absence of single crystals: analysis of powder X-ray diffraction data, guided by solid-state NMR and periodic DFT calculations, reveals a new 2'-deoxyguanosine structural motif.

Derivatives of guanine exhibit diverse supramolecular chemistry, with a variety of distinct hydrogen-bonding motifs reported in the solid state, including ribbons and quartets, which resemble the G-quadruplex found in nucleic acids with sequences rich in guanine. Reflecting this diversity, the solid-state structural properties of 3',5'-bis-O-decanoyl-2'-deoxyguanosine, reported in this paper, reveal a hydrogen-bonded guanine ribbon motif that has not been observed previously for 2'-deoxyguanosine derivatives. In this case, structure determination was carried out directly from powder XRD data, representing one of the most challenging organic molecular structures (a 90-atom molecule) that has been solved to date by this technique. While specific challenges were encountered in the structure determination process, a successful outcome was achieved by augmenting the powder XRD analysis with information derived from solid-state NMR data and with dispersion-corrected periodic DFT calculations for structure optimization. The synergy of experimental and computational methodologies demonstrated in the present work is likely to be an essential feature of strategies to further expand the application of powder XRD as a technique for structure determination of organic molecular materials of even greater complexity in the future.