Nomeda Valevičienė

NMR, Raman and DFT Study of Lyotropic Chromonic Liquid Crystals of Biomedical Interest: Tautomeric Equilibrium and Slow Self-Assembling in Sunset Yellow Aqueous Solutions

Temperature and composition effects in Sunset Yellow FCF (SSY) aqueous solutions were studied by the 1H, 15N NMR as well as Raman spectroscopy passing through all phase transitions between isotropic phase (I) and chromonic phases-nematic (N) and columnar (M). It was shown that the tautomeric equilibrium in SSY is strongly shifted toward the hydrazone form. The corresponding equilibrium constant p KT = 2.5 was deduced using the density functional theory solvent model density model. The dominance of the hydrazone form was confirmed experimentally using the long-range 1H-15N correlation, widely known as heteronuclear multiple bond correlation. The peak found in the 1H NMR spectra at ca. 14.5 ppm can be attributed to the proton in the intramolecular N-H···O bond. The existence of this signal shows that (i) the growth of the SSY aggregates is accompanied by the segregation of water in the intercolumnar areas with no access for exchange with the N-H protons in the internal layers of the columnar stacks and that (ii) the lifetime of those aggregates is ≥10-8 s or even longer. The temperature dependences of H2O chemical shift and Raman O-H stretching band shape show that water confined in the intercolumnar areas behaves as in the neat substance. When the sample is heated and the transition from M phase to N phase occurs, the molecular motion of water is seen to change in a manner similar to that when water is melting. The equilibration time for N + M→ M is very long because of slow supramolecular restructuring, i.e., the growing of columnar stacks and building of hexagonal arrays. If the sample is cooled down to the temperature below N → M transition relatively fast, the structural changes are behind, and the system falls into supercooled state. In this case, the system evolves via long-lasting self-assembling from the supercooled state to the equilibrium. This process affects the shape of the 1H NMR signal and is easy to monitor.

Late arrhythmia in patients with repaired tetralogy of Fallot: who is at risk?

Summary Tetralogy of Fallot (TOF) is the most common cause of cyanotic congenital heart defect. Over the last century, the life expectancy of TOF patients has significantly improved. This, however, has brought new challenges both to patients and their health-care providers, the main of them being late arrhythmia. Ironically, late arrhythmia is predominantly generated due to the fibrotic scars caused by the life-saving surgical repair. Once the first two mainly arrhythmia-free decades after the repair pass, the risk of developing late arrhythmia and, therefore, SCD becomes substantial. Consequently, young adults with repaired Tetralogy of Fallot (rTOF) require careful outpatient monitoring. There have been many attempts to predict the risk of life-threatening arrhythmia in rTOF patients. This has led to the defining of various risk factors, ranging from the widely used QRS prolongation to novel predictors, derived from cardiac magnetic resonance (CMR) based anatomical findings (left ventricular dyssynchrony indexes, right ventricular output tract akinetic length, right ventricular mass-to-volume ratio). The latter predictors have recently established CMR as a tool of high significance in evaluation of rTOF patients. Although the role of Holter monitoring findings in rTOF patient-assessment remains unclear, it may be useful in those who are 25 years and older. Implantable cardioverter–defibrillator (ICD) implantation is the first-line treatment for secondary prevention of sudden cardiac death (SCD). rTOF patients suffer from the highest rate of inappropriate and the lowest rate of appropriate ICD shocks, when compared to other congenital heart diseases. As a consequence, ICD implantation for primary SCD prevention should be carefully weighed. Catheter-based ablation therapy leads to high rate of initial success when abolishing monomorphic ventricular tachycardia and intra-atrial reentrant tachycardia, however recurrence rates remain high.