Conformational polymorphism in a Schiff-base macrocyclic organic ligand : an experimental and theoretical study

Polymorphism in the highly flexible organic Schiffbase macrocycle ligand 3,6,9,17,20,23-hexa-azapentacyclo (23.3.1.1^11,15^.0^2,6^.0^16,20^)triaconta-1(29),9,11,13,15(30),23,-25,27-octaene (DIEN, C24H30N6) has been studied by singlecrystal X-ray diffraction and both solid-state and gas-phase density functional theory (DFT) calculations. In the literature, only solvated structures of the title compound are known. Two new polymorphs and a new solvated form of DIEN, all obtained from the same solvent with different crystallization conditions, are presented for the first time. They all have P1bar symmetry, with the macrocycle positioned on inversion centres. The two unsolvated polymorphic forms differ in the number of molecules in the asymmetric unit Z', density and cohesive energy. Theoretical results confirm that the most stable form is (II\uba), with Z' = 1.5. Two distinct molecular conformations have been found, named \u2018endo\u2019 or \u2018exo\u2019 according to the orientation of the imine N atoms, which can be directed towards the interior or the exterior of the macrocycle. The endo arrangement is ubiquitous in the solid state and is shared by two independent molecules which constitute an invariant supramolecular synthon in all the known crystal forms of DIEN. It is also the most stable arrangement in the gas phase. The exo form, on the other hand, appears only in phase (II\uba), which contains both the conformers. Similarities and differences among the occurring packing motifs, as well as solvent effects, are discussed with the aid of Hirshfeld surface fingerprint plots and correlated to the results of the energy analysis. A possible interconversion path in the gas phase between the endo and the exo conformers has been found by DFT calculations; it consists of a two-step mechanism with activation energies of the order of 30\u2013 40 kJ mol^-1. These findings have been related to the empirical evidence that the most stable phase (II\uba) is also the last appearing one, in accordance with Ostwald\u2019s rule

Sinopse das espécies nativas e subespontâneas de Andropogoneae Dumort. (Poaceae) na Ilha de Santa Catarina, Brasil A synopsis of the Andropogoneae Dumort. (Poaceae) native and subspontaneous to the Island of Santa Catarina, Florianópolis, SC, Brazil

O presente trabalho consiste no levantamento dos táxons da tribo Andropogoneae (Panicoideae - Poaceae) ocorrentes na Ilha de Santa Catarina, Florianópolis, Brasil. A partir da revisão de materiais de herbários e coletas a campo foi confirmada a ocorrência de 10 gêneros e 20 espécies, 17 nativas e duas subespontâneas: Andropogon L. (7 spp.), Bothriochloa Kuntze (2), Eriochrysis P. Beauv. (1), Hyparrhenia Andersson ex E. Fourn. (1), Imperata Cirillo (1), Ischaemum L. (1), Rhytachne Desv. (1), Saccharum L. (3), Schizachyrium Nees (2) e Sorghum Moench (1). Os gêneros Bothriochloa e Rhytachne são registrados pela primeira vez para a Ilha de Santa Catarina. São apresentadas chaves de identificação para gêneros e espécies, ilustrações, informações sobre distribuição geográfica, habitat, período de floração e comentários para cada táxon.<br>The present work is a survey of the taxa in the tribe Andropogoneae (Panicoideae - Poaceae) that occur on the Island of Santa Catarina, Florianópolis, Brazil. Based on a review of herbarium specimens and fieldwork, 20 species were recorded in the following 10 genera: Andropogon L. (7 spp.), Bothriochloa Kuntze (2), Eriochrysis P. Beauv. (1), Hyparrhenia Andersson ex E. Fourn. (1), Imperata Cirillo (1), Ischaemum L. (1), Rhytachne Desv. (1), Saccharum L. (3), Schizachyrium Nees (2) and Sorghum Moench (1). Seventeen of the species are native, and two species are subspontaneous. Bothriochloa and Rhytachne are recorded here, for the first time, for the Island of Santa Catarina. This work provides key to the genera and species, as well as illustrations, information about geographic distribution, habitat, phenology, and comments about each taxon presented in the study

Antiepileptic drug discontinuation by people with epilepsy in the general population

Objective: Rate, reasons, and predictors of antiepileptic drug (AED) discontinuation were investigated in a well-defined cohort of people with epilepsy to verify efficacy and tolerability of treatment up to 20 years from treatment initiation. Methods: The history of AED usage in children and adults with epilepsy registered with 123 family physicians in an area of Northern Italy between 2000 and 2008 was recorded. Cumulative probabilities of AED withdrawal for specific reasons were estimated using cumulative incidence functions. The probabilities of withdrawing for terminal remission, and of achieving sustained remission while still on treatment, were also evaluated. The roles of sex, age at diagnosis, seizure types, duration at diagnosis, and syndrome were assessed with hazard ratios and 95% confidence intervals. Results: Seven hundred thirty-one of 747 individuals were treated with one or more AEDs during the disease course. The three commonest drugs were valproate, carbamazepine, and phenobarbital. Reported reasons for AED withdrawal were, in decreasing order, terminal remission, ineffectiveness, and adverse events. The probability of withdrawing the first AED for terminal remission was 1.0% at 1 year and increased to 20.0% at 20 years. Corresponding rates were 2.9% and 12.6% for ineffectiveness and 0.5% and 3.3% for adverse events. Reasons for withdrawal varied with individuals' age, sex, disease characteristics, and drugs. Significance: The initial AED given was retained in the majority of cases. Terminal remission, lack of efficacy, and adverse effects were, in decreasing order, the commonest reasons for AED discontinuation. Withdrawal could be predicted by age at diagnosis, sex, and clinical characteristics and varies among drugs

Long-term prognosis of epilepsy, prognostic patterns and drug resistance : a population-based study

Background and purpose: Seizures in most people with epilepsy remit but prognostic markers are poorly understood. There is also little information on the long-term outcome of people who fail to achieve seizure control despite the use of two antiepileptic drugs (drug resistance). Methods: People with a validated diagnosis of epilepsy in whom two antiepileptic drugs had failed were identified from primary care records. All were registered with one of 123 family physicians in an area of northern Italy. Remission (uninterrupted seizure freedom lasting 2 years or longer) and prognostic patterns (early remission, late remission, remission followed by relapse, no remission) were determined. Results: In all, 747 individuals (381 men), aged 11 months to 94 years, were followed for 11 045.5 person-years. 428 (59%) were seizure-free. The probability of achieving 2-year remission was 18% at treatment start, 34% at 2 years, 45% at 5, 52% at 10 and 67% at 20 years (terminal remission, 60%). Epilepsy syndrome and drug resistance were the only independent predictors of 2- and 5-year remission. Early remission was seen in 101 people (19%), late remission in 175 (33%), remission followed by relapse in 85 (16%) and no remission in 166 (32%). Treatment response was the only variable associated with differing prognostic patterns. Conclusion: The long-term prognosis of epilepsy is favourable in most cases. Early seizure remission is not invariably followed by terminal remission and seizure outcome varies according to well-defined patterns. Prolonged seizure remission and prognostic patterns can be predicted by broad syndromic categories and the failure of two antiepileptic drugs