Search

The origin of the DNA alkylation selectivity was evaluated through analysis of the reversed and sandwiched analogs of duocarmycin SA. Studies suggested that the ground state destabilization of the substrate disrupted the amide stabilization of the alkylation subunit and increased its reactivity toward nucleophiles. The DNA adenine-thymine minor grove binding mediates the reaction.

The adenine N3 alkylation is mediated by additional characteristics that resemble the imposed stereoelectronic control. Reactive 2,3,10,10a-tetrahydrocyclopropa(d)benzo(f)quinol-5-one (CBQ)-based agents alkylate same sites as the corresponding DSA-, CPI-, DA-, and CI-based agents. These agents have less selectivity among the established alkylation sites and low efficiency to alkylate DNA. Adducts obtained from adenine N3 addition to the least substituted cyclopropane carbon were detected under the relevant conditions of limiting agent.

A new synthesis method is proposed for CC-1065 and duocarmycin analogs that incorporate the 2,3,10, 10a-tetrahydro-1H-cyclopropa(d)benzo(f)quinol-5-one (CBQ) alkylation subunit. The synthesis involves a key 6-exo-trig aryl radical alkene cyclization and subsequent Winstein Ar-3' alkylation. These CBQ-based analogs show marked solvolysis reactivity and mixed solvolysis regioselectivity. These analogs are highly stable and their potent activity is correlated with their chemical stability.

This study focuses on the structure of different supramolecular assemblies formed in the gel phase and in the solid state by a naphthalene-bisimide organogelator: N,N′-di(2-(3,4,5-trioctyloxybenzamido))eth-1-yl naphthalene-1,4,5,8 tetracarboxylic acid bisimide (NDI2). This molecule is formed by a naphthalene bisimide core with symmetric dendrons composed of a flexible alkyl linker, an amide group and a trialkoxyphenyl group. The structure, especially the original polymorphism of this molecule, was correlated with optical and electronic properties in the solid state. Four polymorphs have been prepared in pure form: a dried gel phase, a quenched metastable liquid crystalline phase, a crystalline phase and its sister phase with molten alkyl side chains. The molecular packing of those phases was determined by X-ray diffraction, electron diffraction and high resolution TEM. UV-vis and infrared spectroscopy of the polymorphs uncover the nature of intermolecular π-stacking and H-bonding interactions. In the fibrils of the gel phase, NDI2 molecules form columnar stacks and the fiber axes correspond to the direction of H-bonds between amide groups. The crystalline phase shows an unusual packing where each NDI is π-stacked between two phenyl groups of the adjacent NDI2 molecules. In the metastable LC phase NDI2 molecules assemble into 6/1 supramolecular helices grouped in a frustrated trigonal unit cell. Temperature-dependent TEM, UV-vis and FTIR helped to unveil the molecular reorganization upon transformation between these different polymorphs. Finally, a global phase diagram has been obtained. [ABSTRACT FROM AUTHOR]

Self-assembled helices are used as templates to form helical pores in organic matrices. The imprints are obtained with a high resolution and facilitated by the choice of a high cross-linking density network, which prevents any shrinking of the matrix.

A five-membered ring, associated with the alkylation subunits of CC-1065 and duocarmycin, exhibits geometrical constraints that induce stereoelectronic control on the cleavage of cyclopropane that needs addition to the carbon with least substitution. Chemical and structural properties of N-BOC-CBQ and N-BOC-CB1 reveal the direct relationship of chemical stability to cytotoxic potency.

In iron-deficient conditions, Pseudomonas aeruginosa secretes a major fluorescent siderophore named pyoverdin (Pvd), which after chelating iron(III) is transported back into the cell via its outer membrane receptor FpvA. FpvA is a TonB-dependent transport protein and has the ability to bind Pvd in its apo- or iron-loaded form. The fluorescence properties of Pvd were used to determine the binding kinetics of metal-free and metal-loaded Pvd to FpvA and showed two major features. First, the kinetics of formation of the FpvA-Pvd complex, in vivo and in vitro, are markedly slower compared to those observed for FpvA-Pvd-metal. Second, apo-Pvd and Pvd-metal absorbed with biphasic kinetics to FpvA: the bimolecular step (association of the ligand with the receptor) is followed by a slower step (t½ values of 5 and 34 min for Pvd-metal and Pvd, respectively) that presumably leads to a more stable complex. The most likely explanation for this second step is that the binding of the ligand to the receptor induces a conformational change on FpvA, which may be different, depending on the loading status of Pvd. Analysis of the dissociation of metal-free Pvd from FpvA revealed an energy and a TonB dependency. The dissociation of iron-free Pvd from FpvA in the absence of the TonB protein occurs with slow kinetics in the range of hours, but it can be highly activated by the protonmotive force and TonB to reach a kinetic with a t½ of 1 min. Apparently, under iron-limited conditions, TonB activates the FpvA receptor, resulting in a fast release of iron-free Pvd and generating an unloaded FpvA receptor, competent for binding extracellular Pvd-Fe. [ABSTRACT FROM AUTHOR]

Identifies subtle structural features that contribute to the regioselectivity of the adenine N3 alkylation reaction. Details of some DNA alkylation properties; Analyses on the adenine N3 adduct obtained by thermal depurination; Benefit of the regiochemcial course of the adenine N3 DNA alkylation reaction; Features that complement regioselectivity.

Nanohybrid systems are prepared from organogels of a partially fluorinated molecule and from thermoreversible gels of syndiotactic polystyrene. The thermodynamic behavior, morphology, and structure are investigated by using differential scanning calorimetry, atomic force microscopy, small-angle X-ray scattering (SAXS), and small-angle neutron scattering (SANS). The outcomes of these investigations suggest that the fibrils of the organogel coil around the sPS fibrils, probably through a heterogeneous nucleation process. These systems therefore differ from previously investigated sPS/OPV systems (oligo vinylene phenylene) where OPV fibrils pervade the sPS network.

Investigations into the formation of nanosized structures, particularly nanotubes, by a diamide ester compound are reported. Two aspects are concurrently examined: the role of the solvent and the role of the alkyl chain. The former is addressed by using a benzene derivative (o-xylene) and a totally saturated double ring (trans-decahydronaphthalene) whereas the latter is achieved by replacing the hydrogenous alkyl chain with its fluorinated counterpart while keeping the overall architecture the same. The thermodynamic behavior by differential scanning calorimetry, the morphology by transmission electron microscopy, and the structure by X-ray scattering and small-angle neutron scattering are studied. Despite the identical architecture, the fluorinated molecule does not produce any nanotubes, unlike its totally hydrogenous counterpart. Also, o-xylene prevents the hydrogenous molecule from forming nanotubes, while nanotapes are produced instead. Conversely, the fluorinated molecule produces regularly twisted protostructures in either solvent. Neutron scattering experiments show that the fluorinated alky chain is located within the core of this structure. This suggests that the prerequisite for forming nanotubes relies on the necessity of the alkyl group to point outward.