Teresa M. R. Maria

Self-assembled liquid crystals by hydrogen bonding between bipyridyl and alkylbenzoic acids: solvent-free synthesis by mechanochemistry

A series of thermotropic hydrogen-bonded liquid crystalline structures based on 4,4′-bipyridyl and aliphatic carboxylic acids was prepared by a mechanosynthesis technique. This series was characterised by polarising optical microscope, differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray powder diffraction and 1H NMR relaxometry experimental techniques. In these complexes, the bipyridyl component, a non-mesogenic substance by itself, acts as a double H-bond acceptor, whereas the alkylbenzoic acid acts as a H-bond donor, in a 1:2 proportion. The so-formed complexes exhibit mesophases that are not observed by the single components. A characteristic phase (smectic A) is identified and shown to be affected by the alkyl chain length. The isotropisation temperature is increased by the supramolecular aggregation through the H-bonds.

A thermodynamic based approach on the investigation of a diflunisal pharmaceutical co-crystal with improved intrinsic dissolution rate

A thermodynamic based approach is used to investigate diflunisal+nicotinamide binary and solution mixtures. A 2:1 co-crystal could be prepared by liquid assisted ball mill grinding and by solution crystallization from ethanol. The diflunisal+nicotinamide+ethanol ternary phase diagram points out conditions for co-crystal scaling-up. From the diflunisal+nicotinamide binary phase diagram, besides identification of the co-crystal stoichiometry, two additional useful binary compositions, eutectic mixtures, were characterized. From a solution enthalpy based approach, the enthalpic stabilization of the co-crystal relative to the pure solid components is quantified. Intrinsic dissolution rate, IDR, in test conditions consistent with USP requirements, including those referred in the diflunisal tablet monograph, were carried out, indicating that the co-crystal improves diflunisal IDR by about 20%. The systematic study of diflunisal+nicotinamide mixtures presented in this work is of particular interest due to the relevance of diflunisal, both as a non-steroidal anti-inflammatory drug and also due to the potentiality of orally administrated diflunisal in familial amyloid polyneuropathy.

The low temperature crystalline and glassy states of methyl α-hydroxy-isobutyrate

The low temperature crystalline and glassy phases of methyl α-hydroxy-isobutyrate (MHib) were identified and characterized structurally by differential scanning calorimetry, IR and Raman spectroscopy and molecular modeling. Within the temperature range 13–171 K, MHib exists as a glassy state, where individual molecules may assume the two conformational states previously observed for this compound isolated in an argon matrix and in the liquid phase [S. Jarmelo and R. Fausto, J. Mol. Struct., 1999, 509, 193]. At ca. 171 K, devitrification occurs and a crystalline phase may then be formed [T(onset)≈213 K], the enthalpy of crystallization being ca. 5 kJ mol−1. The crystalline phase was found to exhibit conformational selectivity—in this phase all individual molecules assume a conformation analogous to the most stable conformer found for the isolated molecule and in the liquid (the Syn-syn s-cis conformer, where the H–O–C–C, O–C–CO and OC–O–C dihedrals are ca. 0°). Molecular modeling and Raman data are consistent with a structural unit within the crystal where two MHib molecules form a centrosymmetrical hydrogen bonded dimer. The observed temperature of fusion [Tf(peak)] for the crystal is 240 K.

Structural and vibrational characterization of methyl glycolate in the low temperature crystalline and glassy states

The low temperature phases of methyl glycolate (MGly) were identified and characterized structurally by differential scanning calorimetry, infrared and Raman spectroscopies and molecular modeling. Within the temperature range 13–273 K, MGly may exist in three solid phases. A crystalline phase (I) can be formed from the liquid upon slow cooling [Tonset=222–227 K] or from the low temperature glassy state resulting from fast deposition of the vapour onto a cold substrate at 13 K and subsequent warming. A mixture of the glassy state and crystalline phase (I) is obtained by cooling the liquid at higher cooling rates (vcooling10 K min−1). Upon heating this mixture, devitrification occurs at ca. 175 K, the cold liquid then formed giving rise to a second crystalline variety (II) at Tonset=198–207 K. In the glassy state, individual MGly molecules may assume the two conformational states previously observed for this compound isolated in an argon matrix and in the liquid phase [S. Jarmelo and R. Fausto, J. Mol. Struct., 1999, 509, 183]. On the contrary, the crystalline phase I was found to exhibit conformational selectivity—in this phase, all individual molecules assume a conformation analogous to the most stable conformer found for the isolated molecule and in the liquid (the syn-syn s-cis conformer, where the H–O–C–C, O–C–CO and OC–O–C dihedrals are ca. 0°). In agreement with the spectroscopic results, a molecular modeling analysis reveals that, in this phase, two non-equivalent molecules exhibiting an intramolecular OH···O hydrogen bond exist, which are connected by a relatively strong intermolecular OH···O′ hydrogen bond. Crystalline state II could not be characterized in detail structurally, but the thermodynamic studies seem to indicate that it corresponds to a metastable crystalline form having a more relaxed structure and a slightly higher energy than crystalline state I. The observed temperature of fusion for the two observed crystalline forms are: I, 264 K and II, 260 K.

A calorimetric study of phase transitions for some cyclohexanediols

Phase transitions in solid cis-1,2-cyclohexanediol and trans-1,2-cyclohexanediol and cis/trans-1,4-cyclohexanediol have been studied by differential scanning calorimetry over the temperature range 241 to 383 K. Besides a low-temperature crystalline form, DSC curves show the existence of a solid rotator phase in cis-1,2-cyclohexanediol whilst for the others, only one solid phase is present. Enthalpies of sublimation and vaporization were determined by evaporation into a vacuum using an isothermal calorimeter.

Mn doping-induced structural and magnetic transformations in the antiferroelectric phase of the Bi1−xNdxFeO3 perovskites

X-ray diffraction, differential scanning calorimetry, and magnetization measurements of the Bi0.825Nd0.175Fe1−yMnyO3 (y ≤ 0.3) compounds were carried out to follow the effect of Mn doping on the crystal structure and magnetic properties of the intermediate antiferroelectric and weak ferromagnetic phase of the Bi1−xNdxFeO3 perovskites. Suppression of the antipolar displacements typical of the parent B-site undoped compound followed by stabilization of the GdFeO3-type structure as well as decrease of the antipolar-to-nonpolar transition temperature were found in this series with increasing Mn content. Compositional variation of the spontaneous magnetization in the Bi0.825Nd0.175Fe1−yMnyO3 (y ≤ 0.3) system was shown to have a temperature-dependent character. At room temperature, a close to linear decrease of the spontaneous magnetization takes place with increase of the Mn content. At low temperatures, enhancement of the magnetization is observed with increasing the dopant concentration.

Resolved structures of two picolinamide polymorphs. Investigation of the dimorphic system behaviour under conditions relevant to co-crystal synthesis

The polymorphism of picolinamide, one of the three isomeric pyridinecarboxamides, a group of co-formers with relevance for co-crystal research, has been investigated. Particular attention has been focused on phase transitions brought about in DSC scanning experiments or during ball mill grinding, a common strategy in co-crystal synthesis. Two polymorphs, which the Burger and Ramberger empirical rules predict to be enantiotropically related, were identified. The crystal structure of the room temperature stable polymorph II, Tfus,II = 102.0 °C, was redetermined, while that of the ambient temperature metastable polymorph I, Tfus,I = 106.4 °C, was determined for the first time. This was produced as single crystals by sublimation in an oven at 90 °C. In the crystalline structure of this polymorphic form, hydrogen bonds link the molecules in tetramers, which are then packed in piles along the a axis in an arrangement that has not been found in any of the previously solved crystalline structures of isomeric pyridinecarboxamides. Hirshfeld surface analysis was performed in order to facilitate comparison of the intermolecular contacts in both polymorphs. Ball mill grinding of commercial polymorph II gives rise to different outcomes, depending on the experimental conditions: neat grinding for 120 minutes results in conversion to polymorph I, while the addition of 10 μL of toluene, ethyl acetate, dimethylsulfoxide, methanol, ethanol or isopropyl alcohol and liquid assisted grinding stabilizes polymorph II.

Synthesis of liquid crystals based on hydrogen-bonding of 4-(Octyloxy)benzoic acid with 4-alkylbenzoic acids

ABSTRACT A molecular recognition process has been used to form new mesogenic molecular structures, where intermolecular hydrogen bonding occurs between 4-(octyloxy)benzoic acid (8BAO) and four 4-alkylbenzoic acids (nBAs, n = 2, 5, 6, 7). The synthesis of these complexes has been attained by resorting to mechanochemistry. The resulting materials have been characterized by polarizing optical thermal microscopy, differential scanning calorimetry, vibrational spectroscopy, X-ray powder diffraction, and 1H NMR relaxometry. All the elements of the series show the formation of a mesophase. For one of the complexes, its electro-optical properties have also been assessed, resulting comparable to those of other widely used liquid crystals.

Co-crystals of diflunisal and isomeric pyridinecarboxamides – a thermodynamics and crystal engineering contribution

Diflunisal is an anti-inflammatory, non-steroidal drug, class II of the Biopharmaceutical Classification System, which has recently been the subject of renewed interest due to its potential for use in the oral therapy of familial amyloid polyneuropathy. In this study, a thermodynamics based approach is used to investigate binary mixtures (diflunisal + picolinamide and diflunisal + isonicotinamide) in order to identify solid forms that are potentially useful to improve the biopharmaceutical performance of this active pharmaceutical ingredient. Special emphasis is placed on the research of co-crystals and on the influence of structural changes in the pyridinecarboxamide co-former molecules for co-crystal formation with diflunisal. The thermodynamics based methodology described by ter Horst et al. in 2010 indicates that the formation of co-crystals is thermodynamically feasible for both systems. The binary solid–liquid phase diagrams were built and allowed unequivocal identification of the formation of co-crystals of diflunisal with each of the two isomers and also their stoichiometry of 1 : 1, (diflunisal : co-former) in the case of pyridine-2-carboxamide (picolinamide) and (2 : 1) for pyridine-4-carboxamide (isonicotinamide). Two binary eutectic mixtures, potentially relevant for pharmaceutical application, were also identified. Infrared spectroscopy allowed the identification of the acid⋯N-pyridine heterosynthon in the three co-crystals formed by diflunisal with the isomeric pyridinecarboxamides. However, the results clearly differentiated pyridine-2-carboxamide from pyridine-3-carboxamide and pyridine-4-carboxamide, that share similar crystalline arrangements, at least with respect to the supramolecular synthons.

Synthesis, structure and physical properties of luminescent Pr(III) β-diketonate complexes

Abstract Near infrared lanthanide(III)-based light conversion molecular devices (LCMDs) are emerging as a promising class of materials for organic light-emitting diodes (OLEDs) in some niche technologies. Three of these molecular materials -two highly coordinated Pr3+ β-diketonate monomers and a dimer- are presented and their structure and properties are discussed. Particular emphasis is placed on the solid-to-solid transformation observed for the homodinuclear compound.