Supramolecular Materials

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Hypertension or high-blood pressure is considered a multi- factorial disease being an important worldwide public-health challenge due to its high frequency and concomitant risks of cardiovascular as well as other diseases. It has been identified as the leading risk factor for mortality, being ranked as the third cause of disability-adjusted life-years. The worldwide prevalence of hypertension has been widely reported. During the past century, hypertension has changed from a minor cause of death and disability to one of the major contributors to the global burden of disease.

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Plot from the final Rietveld refinement. Black crosses represent observed data, the red line indicates the calculated pattern and the blue line at the bottom represents the difference between the observed and calculated patterns. Green vertical bars indicate Bragg reflections. After 30° (2θ) the pattern was magnified (5×) for better visualization.

LASSBio-1289 compound has been found to promote intense vasodilation and antihypertensive activity. It is an innovative compound, without structural similarities to the three main classes of calcium antagonists (1,4-dihydropyridines, benzothiazepines and phenylalkylamines) commonly used. A complete knowledge of the structure, including stereochemistry, is essential to lead optimization in drug discovery. For this reason, in this work we determined the crystal structure of this novel vasoactive N-methyl-N-acylhydrazone derivative by means of X-ray powder diffraction data and an ab initio simulating annealing approach, allowing us to observe the relative configuration E of the imine double bond and its conformation as well as its most relevant intermolecular interactions. These findings were also checked by a FTIR analysis and confirmed in solution by NMR. The compound crystallized under a monoclinic crystal system with space group P21/c and unit cell parameters a = 14.5118(3) Å, b = 12.1374(2) Å, c = 7.5498(1) Å, β = 91.113(1)°, V = 1329.53(4) Å3Z = 4, Z′ = 1 and ρcalc = 1.44042(4) g cm−3. Moreover, a crystal morphology prediction, experimentally compared with SEM inferred images, allowed a direct comparison of the microcrystalline habit and quality, allowing a study of the potential solvent effect on the crystal growth. See more in “Structural characterization of LASSBio-1289: a new vasoactive N-methyl-N-acylhydrazone derivative”.

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(a) Molecular structure of LASSBio-1289 compound indicating all non-hydrogen atoms as spheres. Light grey spheres represent the hydrogen atoms (not labelled). (b) Unit cell of LASSBio-1289, along the c-axis, with Z = 4.

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