The Amorphous Form of Salicylsalicylic Acid: Experimental Characterization and Computational Predictability

Amorphous solids challenge our understanding of phase behavior. For small organic molecules, particularly pharmaceuticals, they offer improved solubility and bioavailability. A computational approach to understanding of amorphous stability and ease of formation would be valuable. An apparently ideal test case is salicylsalicylic acid (salsalate), which has been reported to form an amorphous phase that is long-term stable below and above its glass temperature. In this study we report the application of computational crystal structure prediction (CSP) techniques to salsalate, supported by an experimental investigation of the amorphous phase by solid form screening and X-ray derived pair distribution functions (PDFs). CSP reveals a pair of hydrogen bonding motifs that appear to be severely detrimental to the molecule’s ability to pack efficiently and stably, indicating an explanation for salsalate’s formation of a stable amorphous phase. However, experimental data caution against overstating this stability. The amorphous phase is found to crystallize under a wider variety of conditions than has previously been reported. Furthermore the molecule is prone to thermal degradation, giving rise to impurities that may play a role in frustrating crystallization

"Pure shift" 1H NMR, a robust method for revealing heteronuclear couplings in complex spectra

We investigate the utility of “pure shift” techniques in revealing heteronuclear couplings in complex 1H NMR spectra. The results show the technique to be a robust and valuable complement to the standard 1H spectrum, and an attractive alternative to heteronuclear decoupling since the technique is independent of the size of the heteronuclear couplings and the chemical shift range(s) of the heteronuclei involved. We highlight some possible artefacts, and the subtle effects due to the presence of 13C nuclei in otherwise symmetric molecules when bilinear rotational decoupling (BIRD) elements are present in the pulse sequence

Extraction and Visualization of Swirl and Tumble Motion from Engine Simulation Data

Figure 1: Unsteady visualization of vortices from in-cylinder tumble motion in a gas engine and its relationship to the boundary. During the valve cycle (left to right), the piston head that shapes the bottom of the geometry moves down (not shown). The volume rendering shows vortices using a two-dimensional transfer function of λ2 and normalized helicity (legend). The main tumble vortex is extracted and visible as off-center and with an undesired diagonal orientation. The flow structure on the boundary is visualized using boundary topology. A direct correspondence between the volume and boundary visualizations can be observed. In the third image, the intersection of the main vortex with the boundary results in critical points on the front and back walls. Optimizing the combustion process within an engine block is central to the performance of many motorized vehicles. Associated with this process are two important patterns of flow: swirl and tumble motion, which optimize the mixing of fluid within each of an engine’s cylinders. Good visualizations are necessary to analyze the simulation data of these in-cylinder flows. We present a range of methods including integral, feature-based, and imagebased schemes with the goal of extracting and visualizing these tw

Separating the coherence transfer from chemical shift evolution in high-resolution pure shift COSY NMR

Recent developments in data sampling and processing techniques have made it possible to acquire 2‐dimensional NMR spectra of small molecules at digital resolutions in both dimensions approaching the intrinsic limitations of the equipment and sample on a realistic timescale. These developments offer the possibility of enormously increased effective resolution (peak dispersion) and the ability to effectively study samples where peak overlap was previously a limiting factor. Examples of such spectra have been produced for a number of 2‐dimensional techniques including TOCSY and HSQC. In this paper, we investigate some of the problems in applying such techniques to COSY spectra and suggest a modification to the classic experiment that alleviates some of these problems

Using remote substituents to control solution structure and anion binding in lanthanide complexes.

A study of the anion-binding properties of three structurally related lanthanide complexes, which all contain chemically identical anion-binding motifs, has revealed dramatic differences in their anion affinity. These arise as a consequence of changes in the substitution pattern on the periphery of the molecule, at a substantial distance from the binding pocket. Herein, we explore these remote substituent effects and explain the observed behaviour through discussion of the way in which remote substituents can influence and control the global structure of a molecule through their demands upon conformational space. Peripheral modifications to a binuclear lanthanide motif derived from α,α′-bis(DO3 Ayl)-m-xylene are shown to result in dramatic changes to the binding constant for isophthalate. In this system, the parent compound displays considerable conformational flexibility, yet can be assumed to bind to isophthalate through a well-defined conformer. Addition of steric bulk remote from the binding site restricts conformational mobility, giving rise to an increase in binding constant on entropic grounds as long as the ideal binding conformation is not excluded from the available range of conformers

Lanthanide Complexes that Respond to Changes in Cyanide Concentration in Water

Cyanide ions are shown to interact with lanthanide complexes of phenacylDO3A derivatives in aqueous solution, giving rise to changes in the luminescence and NMR spectra. These changes are the consequence of cyanohydrin formation, which is favored by the coordination of the phenacyl carbonyl group to the lanthanide center. These complexes display minimal affinity for fluoride and can detect cyanide at concentrations less than 1 μm. By contrast, lanthanide complexes with DOTAM derivatives display no affinity for cyanide in water, but respond to changes in fluoride concentration

Lanthanide appended rotaxanes respond to changing chloride concentration

Lanthanide appended rotaxanes have been prepared by the CuAAC ‘click’ reaction between an azide appended rotaxane and lanthanide complexes of propargyl DO3A. The resulting complexes are luminescent, and exhibit chloride responsive luminescence behavior consistent with the existence of two independent halide binding pockets, one in the rotaxane cavity and one on the ninth (axial) coordination site of the lanthanide. Strong halide binding to europium gives rise to changes in the relative intensity of the hypersensitive ΔJ = 2 transition compared to the rest of the europium emission spectrum, combined with quenching of the overall intensity of emission as a consequence of non-radiative quenching by the bound halide. The weaker interaction with the rotaxane pocket mediates a subsequent recovery of intensity of the europium centered luminescence despite the considerable separation between the lanthanide and the rotaxane binding pocket

Using Remote Substituents to Control Solution Structure and Anion Binding in Lanthanide Complexes

A study of the anion-binding properties of three structurally related lanthanide complexes, which all contain chemically identical anion-binding motifs, has revealed dramatic differences in their anion affinity. These arise as a consequence of changes in the substitution pattern on the periphery of the molecule, at a substantial distance from the binding pocket. Herein, we explore these remote substituent effects and explain the observed behaviour through discussion of the way in which remote substituents can influence and control the global structure of a molecule through their demands upon conformational space. Peripheral modifications to a binuclear lanthanide motif derived from α,α′-bis(DO3 Ayl)-m-xylene are shown to result in dramatic changes to the binding constant for isophthalate. In this system, the parent compound displays considerable conformational flexibility, yet can be assumed to bind to isophthalate through a well-defined conformer. Addition of steric bulk remote from the binding site restricts conformational mobility, giving rise to an increase in binding constant on entropic grounds as long as the ideal binding conformation is not excluded from the available range of conformers