The reluctant polymorph: investigation into the effect of self-association on the solvent mediated phase transformation and nucleation of theophylline

Little is known concerning the pathway of the crystallization of the thermodynamically stable polymorph of theophylline, form IV. Here we study the reasons why the thermodynamically stable theophylline form IV can be obtained only by slow, solvent mediated phase transformation (SMPT) in specific solvents, and whether the presence of prenucleation aggregates affect the polymorphic outcome. Solution concentration, polymorphic composition and morphology were monitored over time during the transformation from form II to form IV in several solvents. NMR and FTIR spectroscopy were used to detect prenucleation molecular aggregates present in the solutions. It was determined that theophylline self-associates in solvents which are good H-bond donors and the presence of these aggregates hinder the nucleation and phase transformation. SMPT from form II to form IV is a nucleation-growth controlled polymorphic transformation, nucleation is most likely homogenous, and form IV crystals grow along the (001) plane, forming plate-like crystals

Polymorph-Selective Role of Hydrogen Bonding and π-π Stacking in p-Aminobenzoic Acid Solutions

Understanding molecular self-association in solution is vital for uncovering polymorph-selective crystal nucleation pathways. In this paper, we combine solution NMR spectroscopy and molecular dynamics simulations to shed light on the structural and dynamical features of p-aminobenzoic acid (pABA) in solution, and on their role in pABA crystals nucleation. pABA is known to yield different crystal forms (α, and β) depending on solvent choice and supersaturation conditions. NMR reveals that dominant interactions stabilizing pABA oligomers are markedly solvent-dependent: in organic solvents, hydrogen bonds dominate, while water promotes π-πstacking. Despite this clear preference, both types of interactions contribute to the variety of self-associated species in all solvents considered. MD simulations support this observation and show that pABA oligomers are short-lived and display a fluxional character, therefore indicating that the growth unit involved in pABA crystallization is likely to be a single molecule. Nevertheless, we note that the interactions dominating in pABA oligomers are indicative of the polymorph obtained from precipitation. In water, at low pABA concentrations - conditions that are known to yield crystals of the β form - carboxylic-carboxylic hydrogen bonds are exclusively asymmetric. At higher pABA concentration conditions in which the crystallization is known to yield the α form - a small but statistically significant fraction of symmetric carboxylic-carboxylic hydrogen-bonded dimers is present. We interpret the presence of these interactions in solvated pABA oligomers as indicative of the fact that a simultaneous and complete desolvation of two carboxylic groups, necessary to form the symmetric hydrogen-bonded dimer typical of the α crystal form, is accessible, therefore directing the nucleation pathway toward the nucleation of α-pABA

FIBRE OPTICAL COUPLER SIMULATION BY COMSOL MULTIPHYSICS SOFTWARE

Funding: The research has been supported by the European Regional Development Fund project No.1.1.1.1/18/A/068. The Institute of Solid State Physics, University of Latvia as a Center of Excellence has received funding from the European Union’s Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017-TeamingPhase2 under grant agreement No. 739508, project CAMART2.The paper presents a simulation model developed for a special optical coupler intended for coupling radiation from signal and pump sources used for the realization of cladding-pumped doped fibre amplifiers. The model is developed in COMSOL Multiphysics and used to assess the pumping efficiency for different side pumping angles and different numbers of electromagnetic modes. The obtained results show that the highest pumping efficiency, above 75 %, is achieved for 5–14 modes when two fibres representing the pump source and the signal source form a 10-degree angle between their central axes. The search for the optimal number of modes corresponds to the development trend in optical coupler technology where the multimode pumping by light-emitting diode (LED) replaces the classical scheme with a single-mode pumping by a laser diode (LD). © 2022 Sciendo. All rights reserved. --//-- This is an open access article Elsts E., Supe A., Spolitis S., Zakis K., Olonkins S., Udalcovs A., Murnieks R., Senkans U., Prigunovs D., Gegere L., Draguns K., Lukosevics I., Ozolins O., Grube J., Bobrovs V. FIBRE OPTICAL COUPLER SIMULATION BY COMSOL MULTIPHYSICS SOFTWARE (2022) Latvian Journal of Physics and Technical Sciences, 59 (5), pp. 3 - 14, DOI: 10.2478/lpts-2022-0036 published under the CC BY-NC-ND 4.0 licence.ERDF No.1.1.1.1/18/A/068; The Institute of Solid State Physics, University of Latvia as a Center of Excellence has received funding from the European Union’s Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017-TeamingPhase2 under grant agreement No. 739508, project CAMART2

Ultrafast Fragment Screening Using Photo-Hyperpolarized (CIDNP) NMR

While nuclear magnetic resonance (NMR) is regarded asa referencein fragment-based drug design, its implementation in a high-throughputmanner is limited by its lack of sensitivity resulting in long acquisitiontimes and high micromolar sample concentrations. Several hyperpolarizationapproaches could, in principle, improve the sensitivity of NMR alsoin drug research. However, photochemically induced dynamic nuclearpolarization (photo-CIDNP) is the only method that is directly applicablein aqueous solution and agile for scalable implementation using off-the-shelfhardware. With the use of photo-CIDNP, this work demonstrates thedetection of weak binders in the millimolar affinity range using lowmicromolar concentrations down to 5 mu M of ligand and 2 mu Mof target, thereby exploiting the photo-CIDNP-induced polarizationtwice: (i) increasing the signal-to-noise by one to two orders inmagnitude and (ii) polarization-only of the free non-bound moleculeallowing identification of binding by polarization quenching, yieldinganother factor of hundred in time when compared with standard techniques.The interaction detection was performed with single-scan NMR experimentsof a duration of 2 to 5 s. Taking advantage of the readiness of photo-CIDNPsetup implementation, an automated flow-through platform was designedto screen samples at a screening rate of 1500 samples per day. Furthermore,a 212 compounds photo-CIDNP fragment library is presented, openingan avenue toward a comprehensive fragment-based screening method.ISSN:0002-7863ISSN:1520-512

Performance enhancement of multi-core fiber transmission using real-time FPGA based pre-emphasis

We experimentally demonstrate pre-emphasis based performance for a 2 km long 7-core multicore fiber link. Simultaneous transmission below the FEC threshold is achievable for all cores by using signal equalization in a FPGA