Search for: All records

An arrayed combination of water-soluble deep cavitands and cationic dyes has been shown to optically sense insect pheromones at micromolar concentration in water. Machine learning approaches were used to optimize the most effective array components, which allows differentiation between small structural differences in targets, including between different diastereomers, even though the pheromones have no innate chromophore. When combined with chiral additives, enantiodiscrimination is possible, dependent on the size and shape of the pheromone. 

NMR-assisted crystallography—the integrated application of solid-state NMR, X-ray crystallography, and first-principles computational chemistry—holds significant promise for mechanistic enzymology: by providing atomic-resolution characterization of stable intermediates in enzyme active sites, including hydrogen atom locations and tautomeric equilibria, NMR crystallography offers insight into both structure and chemical dynamics. Here, this integrated approach is used to characterize the tryptophan synthase α-aminoacrylate intermediate, a defining species for pyridoxal-5′-phosphate–dependent enzymes that catalyze β-elimination and replacement reactions. For this intermediate, NMR-assisted crystallography is able to identify the protonation states of the ionizable sites on the cofactor, substrate, and catalytic side chains as well as the location and orientation of crystallographic waters within the active site. Most notable is the water molecule immediately adjacent to the substrate β-carbon, which serves as a hydrogen bond donor to the ε-amino group of the acid–base catalytic residue βLys87. From this analysis, a detailed three-dimensional picture of structure and reactivity emerges, highlighting the fate of the L-serine hydroxyl leaving group and the reaction pathway back to the preceding transition state. Reaction of the α-aminoacrylate intermediate with benzimidazole, an isostere of the natural substrate indole, shows benzimidazole bound in the active site and poised for, but unable to initiate, the subsequent bond formation step. When modeled into the benzimidazole position, indole is positioned with C3 in contact with the α-aminoacrylate C β and aligned for nucleophilic attack. Here, the chemically detailed, three-dimensional structure from NMR-assisted crystallography is key to understanding why benzimidazole does not react, while indole does. 

A water-soluble host molecule can bind tetrahydrocannabinol ( Δ9-THC ) and its metabolites in aqueous solution. By pairing this recognition event in a sensing array with fluorescent reporters and varying external mediators, pattern recognition-based detection is possible, which allows selective discrimination of the THC metabolites. The selective sensing can be performed in aqueous solution with micromolar sensitivity, as well as in biofluids such as urine and saliva. Metabolites as similar as Δ8- and Δ9-THC , differing only in the position of a double bond, can be distinguished. 

Arrayed cavitand:fluorophore sensor complexes can selectively sense small citrulline modifications at arginine residues on post-translationally modified peptides. The sensor can differentiate between different numbers of citrulline modifications, and a simple two-fluorophore, 6-component array can effect cross-reactive discrimination between single modifications in aqueous solution. 

A host–guest based fluorescence sensor array can sense small differences in protein structure. The combination of three cavitand hosts and two fluorophores to form a 4-component array is sufficient to fully discriminate five structurally similar Ig protein isotypes. The array can be applied to recognize Ig deficiencies in serum, when combined with a Protein L-based extraction process, allowing analysis of immunodeficiency in a simpler, lower cost manner than tests that require multiple specific antibodies. 

Crystals composed of photoreactive molecules represent a new class of photomechanical materials with the potential to generate large forces on fast timescales. An example is the photodimerization of 9- tert -butyl-anthracene ester ( 9TBAE ) in molecular crystal nanorods that leads to an average elongation of 8%. Previous work showed that this expansion results from the formation of a metastable crystalline product. In this article, it is shown how a novel combination of ensemble oriented-crystal solid-state NMR, X-ray diffraction, and first principles computational modeling can be used to establish the absolute unit cell orientations relative to the shape change, revealing the atomic-resolution mechanism for the photomechanical response and enabling the construction of a model that predicts an elongation of 7.4%, in good agreement with the experimental value. According to this model, the nanorod expansion does not result from an overall change in the volume of the unit cell, but rather from an anisotropic rearrangement of the molecular contents. The ability to understand quantitatively how molecular-level photochemistry generates mechanical displacements allows us to predict that the expansion could be tuned from +9% to −9.5% by controlling the initial orientation of the unit cell with respect to the nanorod axis. This application of NMR-assisted crystallography provides a new tool capable of tying the atomic-level structural rearrangement of the reacting molecular species to the mechanical response of a nanostructured sample. 

A synergistic combination of a deep cavitand host, fluorophore guests and transition metal ions can be used to sense small molecule thiols of biological interest with good efficiency and selectivity in complex aqueous media.