This work has shown spin selectivity in electron transfer (ET) of diastereomers of (R,S)-naproxen-(S)-N-methylpyrrolidine and (R,S)-naproxen-(S)-tryptophan dyads. Photoinduced ET in these dyads is interesting because of the still unexplained phenomenon of stereoselectivity in the drug activity of enantiomers. The chemically induced dynamic nuclear polarization (CIDNP) enhancement coefficients of (R,S)-diastereomers are double those of the (S,S)-analogue. These facts are also interesting because spin effects are among the most sensitive, even to small changes in spin and molecular dynamics of paramagnetic particles. Therefore, CIDNP reflects the difference in magnetoresonance parameters (hyperfine interaction constants (HFIs), g-factor difference) and lifetimes of the paramagnetic forms of (R,S)- and (S,S)-diastereomers. The difference in HFI values for diastereomers has been confirmed by a comparison of CIDNP experimental enhancement coefficients with those calculated. Additionally, the dependence of the CIDNP enhancement coefficients on diastereomer concentration has been observed for the naproxen-N-methylpyrrolidine dyad. This has been explained by the participation of ET in homo-(R,S-R,S or S,S-S,S) and hetero-(R,S-S,S) dimers of dyads. In this case, the effectivity of ET, and consequently, CIDNP, is supposed to be different for (R,S)- and (S,S)-homodimers, heterodimers, and monomers. The possibility of dyad dimer formation has been demonstrated by using high-resolution X-ray and NMR spectroscopy techniques.

Two polymorphs of tolazamide, N-[(azepan-1-ylamino)carbonyl]-4-methylbenzenesulfonamide, a sulfonylurea anti-diabetic drug, have different densities and molecular packings. Polymorph II converts into polymorph I in the solid state on heating or via recrystallization if solvent-assisted. The effect of pressure on the two forms and the possibility of a transformation to a denser form on compression have been studied.No phase transitions have been observed in either of the forms in a pentane-isopentane mixture (when no recrystallization is possible). Polymorph II recrystallized partly into a denser polymorph I in methanol at 0.1 GPa, but the transformation stopped at an early stage. Solid state DFT calculations of the two forms as well as conformational landscape investigation in the gas phase were used to rationalize this result. The anisotropic pressure-induced strain of the two polymorphs has been compared in relation to changes in the hydrogen bond geometry and the behavior of stacking interactions. † Electronic supplementary information (ESI) available: Information on tolazamide crystallization in methanol, low-temperature experiments, details of computational techniques and other data for tolazamide polymorphs: summary of the structural data at multiple pressures and temperatures; data on H-bonds and stacking interactions under pressure, parameters of the equations of state, and information on the strain ellipsoids; figures presenting the tolazamide molecule conformational landscape, conformational disorder in form II and pressure dependencies of tolazamide polymorphs' enthalpies. CCDC 1495203-1495210 and 1493069-1493078. For ESI and crystallographic data in CIF or other electronic format see

In the present case study of tolazamide we illustrate how many seemingly contradictoryr esults that have been obtained from experimental observationsa nd theoretical calculationsc an finally startf ormingaconsistent picture: a" puzzle put together". For many years, tolazamide was considered to have no polymorphs. This made this drug substance unique amongt he large familyo fs ulfonylureas, which was known to be significantly more pronet op olymorphism than many other organic compounds. The present work employs ab road and in-deptha nalysist hat includest he use of optical microscopy,s ingle-crystal and powder X-ray diffraction,I Ra nd Ramans pectroscopies, DSC, semiempiricalP IXEL calculations and DFT of three polymorphs of tolazamide. This case study showsh ow the polymorphs of amolecular crystalc an be overlooked even if discovered serendipitously on one of numerous crystallizations, and how very different molecular packings can be practically isoenergetic but still crystallize quite selectively and transform one into anotherirreversibly upon heating.

Crystals of maleates of three amino acids with hydrophobic side chains [L-leucenium hydrogen maleate, C6H14NO2(+)·C4H3O4(-), (I), L-isoleucenium hydrogen maleate hemihydrate, C6H14NO2(+)·C4H3O4(-)·0.5H2O, (II), and L-norvalinium hydrogen maleate-L-norvaline (1/1), C5H11NO2(+)·C4H3O4(-)·C5H12NO2, (III)], were obtained. The new structures contain C2(2)(12) chains, or variants thereof, that are a common feature in the crystal structures of amino acid maleates. The L-leucenium salt is remarkable due to a large number of symmetrically non-equivalent units (Z' = 3). The L-isoleucenium salt is a hydrate despite the fact that L-isoleucine is a nonpolar hydrophobic amino acid (previously known amino acid maleates formed hydrates only with lysine and histidine, which are polar and hydrophilic). The L-norvalinium salt provides the first example where the dimeric cation L-Nva...L-NvaH(+) was observed. All three compounds have layered noncentrosymmetric structures. Preliminary tests have shown the presence of the second harmonic generation (SGH) effect for all three compounds.

Metacetamol is a structural isomer of the widely used drug paracetamol and is being considered as a promising alternative to the latter because of its lower toxicity. Due to the importance of the well-known polymorphism of paracetamol, an investigation of the polymorphism of metacetamol was successfully undertaken. A new polymorph of metacetamol has been discovered and extensively characterised using a variety of analytical techniques (IR-and Raman spectroscopy, UV-visible optical spectroscopy, X-ray powder and single-crystal diffraction, TGA and DSC). A procedure for the reliable and reproducible preparation of the new polymorph is described. Its properties and crystal structure are compared with those of the previously known polymorph, as well as with those of paracetamol. CrystEngComm This journal isScheme 1 Molecular structures of metacetamol (left) and paracetamol (right) containing the same characteristic functional groups.

The present study delivers a computational approach for the understanding of the mechanism of phase transitions between polymorphs of small organic molecules. By using state of the art periodic DFT calculations augmented with dispersion corrections and an external stress tensor together with gas-phase cluster calculations, we thoroughly explained the reversible phase transitions of three polymorphs of the model system, namely crystalline l-serine in the pressure range up to 8 GPa. This study has shown that at the macroscopic level the main driving force of the phase transitions is the decrease in the volume of the crystal unit cell, which contributes to the enthalpy difference between the two forms, but not to the difference in their internal crystal energies. At the microscopic level we suggest that hydrogen bond overstrain leads to a martensitic-like, cooperative, displacive phase transition with substantial experimental hysteresis, while no such overstrain was found for the "normal type", atom per atom, reconstructive phase transition. The predicted pressures for the phase transitions deducted by the minimum enthalpy criterion are in reasonable agreement with the observed ones. By delivering unambiguous explanations not provided by previous studies and probably not accessible to experiment, this work demonstrates the predictive and explanatory power of quantum chemistry, confirming its indispensable role in structural studies.

A number of modifications to traditional techniques are suggested in order to overcome problems that frequently arise when growing crystals from solution. These improvements, and their combination, help to avoid problems such as poor nucleation, the spontaneous precipitation of many poor-quality small powder-like crystals, crystals adhering to the crystallization vessel or to each other, and chemical degradation of the solution. The proposed techniques can be used to crystallize desirable metastable polymorphs reliably. None of the suggested methods demands the usage of any special or expensive equipment, or specific skills, and they can be implemented in the chemistry curriculum even at secondary school level. Examples are given for the crystallization of small organic molecules such as carboxylic acids, amino acids, pharmaceuticals etc., but the same techniques are applicable to other classes of compound.

l-Leucinium hydrogen maleate crystals are very plastic at ambient conditions. Here it is shown that this plasticity is preserved at least down to 77 K. The structural changes in the temperature range 293-100 K were followed in order to rationalize the large anisotropic plasticity in this compound. To the best of our knowledge, this is the first reported example of an organic compound remaining so plastic at cryogenic conditions.