18-crown-6-sodium cholate complex: thermochemistry, structure and stability

18-crown-6, one of the most relevant crown ethers, and sodium cholate, steroidal surfactant classified as natural bile salt, are components of novel, synthesized coordination complex ; 18-crown-6-sodium cholate (18C6•NaCh). Like crown ethers, bile salts act as building blocks in supramolecular chemistry in order to design new functionalized materials with a desired structure and properties. In order to obtain thermal behavior of this 1:1 coordination complex, thermogravimetry and differential thermal analysis were used, as well as microscopic observations and differential scanning calorimetry. Temperature dependent infrared spectroscopy (IR) gave a detailed view into phase transitions. The structures during thermal treatment were observed with powder X-ray diffraction, and molecular models of the phases are made. Hard, glassy, colorless compound 18C6•NaCh goes through crystalline – crystalline polymorphic phase transitions at higher temperatures. The room temperature phase is indexed to a triclinic lattice, while in the high temperature phases molecules take randomly one of the two different configurations in the unit cell, resulting in the 2-fold symmetry. The formation of cholesteric liquid crystalline phase occurs simultaneously with partial decomposition, followed by the isotropisation with simultaneous and complete decomposition at much higher temperature, as obtained by IR. The results provide valuable information about the relationship between molecular structure, thermal properties, and stability of the complex, indicating the importance of an appropriate choice of cation, amphiphilic, and crown ether unit in order to synthesize compounds with desired behavior

Supramolecular variations on a molecular theme: The structural diversity of phosphazenes (RNH)6P3N3 in the solid state

Herein, we introduce an extremely 'soft' tecton, which interacts via 'soft' synthons displaying an unprecedented variety of supramolecular architectures in the solid state. Hexakis(organoamino) cyclotriphosphazene derivatives, (RNH)6P3N3, contain a polar core comprising an equatorial belt of three ring nitrogen atoms and six NH functions which is sandwiched between hemispheres of lipophilic substituents R. A range of derivatives equipped with hydrocarbon side chains were synthesised and structurally characterised including R = tert-butyl (1), cyclohexyl (2), iso-propyl (3), benzyl (4), 2-phenylethyl (5), iso-butyl (6), phenyl (7), p-tolyl (8), n-propyl (9), allyl (10), propargyl (11) and methyl (12). The study shows that subtle modifications of the lipophilic periphery lead to considerable changes in the solid-state aggregation pattern. With the exception of 1 all solid-state structures show intermolecular NH mellip; N bonding with motifs containing one, two, three and four H-bridges. Supramolecular architectures include monomer (1), dimer (2), cyclic hexamer (3), zigzag chain (4, 6), linear chain (5·thf, 7, 8) double chain (9), graphite-type sheet (10), rectangular grid (11) and hexagonal close-packed sheet (12). The structural variety is due to easy rotation around exocyclic P-N bonds, which allows variable directionalities of all six N-H bonds. M.O. calculations on the gas phase dimer of (H2N)6P3N3 mirror the H-bridging motifs observed in crystal structures of (RNH)6P 3N3 derivatives

Acridinediones: Selective and potent inhibitors of the malaria parasite mitochondrial bc(1) complex

The development of drug resistance to affordable drugs has contributed to a global increase in the number of deaths from malaria. This unacceptable situation has stimulated research for new drugs active against multidrug-resistant Plasmodium falciparum parasites. In this regard, we show here that deshydroxy-1-imino derivatives of acridine (i.e., dihydroacridinediones) are selective antimalarial drugs acting as potent (nanomolar K-i) inhibitors of parasite mitochondrial bc(1) complex. Inhibition of the bc(1) complex led to a collapse of the mitochondrial membrane potential, resulting in cell death (IC50 similar to 15 nM). The selectivity of one of the dihydroacridinediones against the parasite enzyme was some 5000-fold higher than for the human bc(1) complex, significantly higher (similar to 200 fold) than that observed with atovaquone, a licensed bc(1)-specific antimalarial drug. Experiments performed with yeast manifesting mutations in the bc(1) complex reveal that binding is directed to the quinol oxidation site (Q(o)) of the bc(1) complex. This is supported by favorable binding energies for in silico docking of dihydroacridinediones to P. falciparum bc(1) Q(o). Dihydroacridinediones represent an entirely new class of bc(1) inhibitors and the potential of these compounds as novel antimalarial drugs is discussed