Stereochemical aspects of crystalline synthetic macromolecules

The most relevant conformational aspects of different skeletal sequences of macromolecules in the crystalline state are discussed. The general importance of the minimum intramolecular energy rule is stressed. Because of the higher energy barriers separating the rotational isomers, sequences of C atoms show a much greater tendency to regular (i.e. “staggered”) conformations than those involving CH₂O or CH₂N bonds. This is reflected in the surprisingly large variety of conformational polymorphs observed especially in polyoxides and in polyformals.     

Identification of the Schistosoma mansoni molecular target for the antimalarial drug artemether

Plasmodium falciparum and Schistosoma mansonii are the parasites responsible for most of the malaria and schistosomiasis cases in the world. Notwithstanding their many differences, the two agents have striking similarities in that they both are blood feeders and are targets of an overlapping set of drugs, including the well-known artemether molecule. Here we explore the possibility of using the known information about the mode of action of artemether in Plasmodium to identify the molecular target of the drug in Schistosoma and provide evidence that artemether binds to SmSERCA, a putative Ca2?-ATPase of Schistosoma . We also predict the putative binding mode of the molecule for both its Plasmodium and Schistosoma targets. Our analysis of the mode of binding of artemether to Ca2?-ATPases also provides an explanation for the apparent paradox that, although the molecule has no side effect in humans, it has been shown to possess antitumoral activity.     

Pros and Cons of the Cannabinoid System in Cancer: Focus on Hematological Malignancies

The endocannabinoid system (ECS) is a composite cell-signaling system that allows endogenous cannabinoid ligands to control cell functions through the interaction with cannabinoid receptors. Modifications of the ECS might contribute to the pathogenesis of different diseases, including cancers. However, the use of these compounds as antitumor agents remains debatable. Pre-clinical experimental studies have shown that cannabinoids (CBs) might be effective for the treatment of hematological malignancies, such as leukemia and lymphoma. Specifically, CBs may activate programmed cell death mechanisms, thus blocking cancer cell growth, and may modulate both autophagy and angiogenesis. Therefore, CBs may have significant anti-tumor effects in hematologic diseases and may synergistically act with chemotherapeutic agents, possibly also reducing chemoresistance. Moreover, targeting ECS might be considered as a novel approach for the management of graft versus host disease, thus reducing some symptoms such as anorexia, cachexia, fatigue, anxiety, depression, and neuropathic pain. The aim of the present review is to collect the state of the art of CBs effects on hematological tumors, thus focusing on the essential topics that might be useful before moving into the clinical practice.     

The configurational free energy of a polymer chain

The configurational, or elastic, free energy A_el of a polymer chain is discussed in terms of the Fourier configurational approach. The importance of accounting for all degrees of freedom of the chain is shown in comparison with affine mean-field theories and with scaling theories of chain expansion and contraction. In case of strong contraction the chain does show neither affinity nor self-similarity, and we get A_el ∼ N^1/3, N being the number of chain bonds. Conversely, in case of good-solvent expansion we find A_el ∼ N. The same result holds in the vicinity of the Θ-temperature, where A_el is also proportional to [(T − Θ)/T]².     

Chiral crystallization of helical polymers

Crystallization of achiral or racemic helical polymers in chiral crystals is quite frequent and while in some cases it may relate to the thermodynamic stability of the chiral polymorph, in others it must be associated with kinetic factors. Analysis of the available literature data suggests that in the second instance a key role must be played by the nucleation step, i.e. specifically by the formation of precrystalline entities. Furthermore a survey of the chiral crystal structures for helical polymers evidences that they are frequently characterized by a quasi-hexagonal packing. The hexagonality index H, defined as the ratio of the largest to the smallest distance between the axis of the reference helix and its six nearest neighbors, appears to be a reliable indicator of the presence of helices of a single handedness or, respectively, of both in a given crystal structure. A detailed analysis of the general energetic and entropic factors favouring chiral crystallization of helical polymers is carried out. It is shown that a hexagonal or pseudo-hexagonal arrangement (i.e. the six-fold coordination) in either the crystalline or in a precrystalline state, promotes chiral crystallization and is in its own turn favoured by clustering of isochiral helices.     

Molecular dynamics simulation of semirigid polymers

The chain rigidity of poly(p-hydroxybenzoate) was estimated through the theoretical evaluation of its persistence length (L_p). A non-Brownian molecular dynamics (MD) simulation of an isolated chain with 20 monomeric units was performed. The sampled conformational population was analyzed and the orientational correlation function between monomeric units along the chain was calculated. An algorithm based on the worm-like chain model was applied to evaluate the persistence length. The results were compared with those obtained from equilibrium models like the freely-rotating-chain and the rotational-matrix method with fluctuations. Equilibrium models give different results depending on the degree of accuracy used in describing the monomeric unit. The inclusion of thermal fluctuations is crucial to obtain realistic results. These coincide with those given by MD simulation when only nearest-neighbour orientational correlations are taken into account: inclusion of higher-order correlation terms leads to lower values of the persistence length. The origin of this discrepancy was investigated. The MD simulation results are characterized by an overrepresentation of conformations with a short end-to-end distance resulting from an anomalous energy concentration in the first bending mode of the chain. In analogy with previous simulation results from systems characterized by a week coupling amoung their degrees of freedom, failure in the energy equipartition is proposed as a likely explanation of the anomalous dynamical behaviour.