The structure of the lipoplex formed from DNA and the sugar-based cationic gemini surfactant 1, which exhibits excellent transfection efficiency, has been investigated in the pH range 8.8-3.0 utilizing small-angle X-ray scattering (SAXS) and cryo-electron microscopy (cryo-TEM). Uniquely, three well-defined morphologies of the lipoplex were observed upon gradual acidification: a lamellar phase, a condensed lamellar phase, and an inverted hexagonal (H(II)) columnar phase. Using molecular modeling, we link the observed lipoplex morphologies and physical behavior to specific structural features in the individual surfactant, illuminating key factors in future surfactant design, viz., a spacer of six methylene groups, the presence of two nitrogens that can be protonated in the physiological pH range, two unsaturated alkyl tails, and hydrophilic sugar headgroups. Assuming that the mechanism of transfection by synthetic cationic surfactants involves endocytosis, we contend that the efficacy of gemini surfactant 1 as a gene delivery vehicle can be explained by the unprecedented observation of a pH-induced formation of the inverted hexagonal phase of the lipoplex in the endosomal pH range. This change in morphology leads to destabilization of the endosome through fusion of the lipoplex with the endosomal wall, resulting in release of DNA into the cytoplasm.

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Functionalized gluconamides and their metal complexes are shown to give supramolecular assemblies, in some cases chiral, and to form organogels in a large variety of organic solvents, e.g. methacrylate mixtures which can be poly merized, as well as o-xylene, chloroform, ethyl acetate, ethanol and tetrahydrofuran.

Cytochrome P450 is one of Nature's oxidative workhorses and is utilized in a wide variety of roles, one of the most important being the detoxification of foreign bodies within the liver. As a result of its fundamental importance it has been extensively investigated, modeled and mimicked over the past 30 years, and more recently modified and mutated. During this period the complexity, beauty and activity of the biomimetic model systems developed in the laboratory have grown considerably. The synthetic analogues of the cytochrome P450 system have evolved dramatically from simple sterically hindered porphyrin models through to more complex model systems combining cavities such as cyclodextrins and utilizing the interactions between host and guest to generate substrate selectivity and stereoselectivity in product formation. More recently, researchers have tried to combine knowledge obtained from the developing field of supramolecular chemistry and from biochemistry to construct self-assembling systems that contain all the components of the natural system and even utilize molecular oxygen as the oxidant. These systems are successful in that they can achieve turnover numbers comparable to those observed for the natural system. The history of these developments and the current 'state-of-the-art' in construction of mimics of the natural enzyme will be presented.

Multiple in situ and time-resolved spectroscopic techniques (EDXAFS, UV-vis, EPR, and NMR), with a focus on simultaneously acquired EDXAFS and time-resolved UV-vis, are described to reveal detailed structural and electronic information on reaction intermediates of an important Cu(II)-catalyzed N-arylation of imidazole. The N-arylation of imidazole was performed in a NMP/ H 2 O solvent mixture, at ambient temperature and atmosphere, using the commercially available Cu catalyst [Cu(OH)(TMEDA)] 2 Cl 2 (I). The spectroscopic study resulted in the characterization of most reaction intermediates, and a novel mechanism for the Cu(II)-catalyzed arylation reaction is proposed. The first and selectivity-determining step is the reaction of the dimeric Cu(II) starting complex with imidazole, forming a mononuclear Cu(II)(imidazole) intermediate, II. After subsequent addition of phenylboronic acid, we propose the formation of a Cu(III)(imidazolate)(phenyl) intermediate, III, which after reductive elimination forms the phenylimidazole product, and a known Cu(I) monomeric species, IV, is identified. Finally, this Cu species is reoxidized, forming back an equilibrium mixture of Cu(II) mononuclear and dinuclear complexes. Inhibition of the reaction by imidazole and phenylimidazole is observed. The phenylboronic acid is, in combination with H 2 O, involved in the oxidation and reoxidation steps in the described catalytic cycle.

A detailed mechanistic study on the M ukaiyam a epoxidation of lim onene with dioxygen as oxidant, bis(acetylacetonato)nickel(II) as catalyst, and an aldehyde as co-reagent is reported.All m ajor products of the reaction have been quantitatively identified, both with i-butyraldehyde and 2-methylundecanal as co-reacting aldehydes. Lim onene epoxide is form ed in good yield. The main products evolving from the aldehyde are carboxylic acid, CO2, C O , and low er m olecular w eight ketone and alcohol (K+A). A m echanism is proposed in which an acylperoxy radical form ed by the autoxidation of the aldehyde is the epoxidizing species. The observation of carbon dioxide and (K+A) in a 1:1 m olar ratio supports this mechanism. CO 2 and (K+A) are form ed in m olar amounts of 50-60% with respect to the am ount of epoxide produced, indicating that epoxidation not only takes place via acylperoxy radicals, but also via a peracid route.Cyclohexene epoxidation was also investigated with a num ber of different metal com plexes as catalysts. Cyclohexene is very sensitive for allylic oxidation, which provides inform ation about the action of the catalyst, e.g. metals which form strongly oxidizing stable high valence com plexes are more likely to induce allylic oxidation. Color changes in the reaction m ixture indicate the presence of such high valence species. In the case of nickel, it was found that high valence com plexes are absent during the reaction which is in line with the fact that this metal displays the highest selectivity for epoxide. A mechanism which accounts for the observations is presented.

Gluconamides can be easily functionalized to give a variety of compounds that form organogels with a high viscosity. N-n-octyl-D-gluconamide-6-benzoate gelates a large variety of organic solvents, including 1,2-xylene, chloroform, ethyl acetate, and ethanol, to form gels which are, in some cases, stable even above the boiling point of the pure solvent. The 2-methoxy, 6-imidazolyl, 6-acetyl, and 6-cyclohexanoyl derivatives also show gelation, but the 2,4;3,5-dimethylene-protected derivatives do not. Detailed 1 H NMR, IR, and X-ray powder diffraction studies reveal that the molecules of most gelators are packed in a head-to-tail fashion. If there is, however, the possibility to form interlayer hydrogen bonds, as in the case of N-n-octyl-D-gluconamide or N-n-octyl-D-gluconamide-6-(3pyridyl carboxylate), the molecules are packed head-to-head. Some gluconamides, e.g., those with aliphatic substituents, express their molecular chirality in the supramolecular structures, whereas others, in particular those containing a large aromatic substituent on carbon atom C 6 , yield nonchiral aggregates, probably due to interfering π-π stacking interactions of the substituents. DSC experiments show that the formation of the gels is an entropy-driven process.

The incorporation characteristics of three simple tetraarylporphyrins into bilayers of dioctadecyldimethylam monium surfactants was studied by UV-vis, fluorescence, and EPR spectroscopy. The porphyrins used are tetraphenylporphyrin (TPP), tetrakis(4-(hexadecyloxy)phenyl)porphyrin (THPP), and tris(4-(hexadecyloxy)-phenyl)(4-methylpyridinium)porphyrin tosylate (TrHPyP). At low porphyrin to surfactant molar ratios (<5 x 10"4) the porphyrins show a strong fluorescence. Increasing this ratio to 5 X 10~3 causes a change in the UV-vis spectra and a decrease of the fluorescence intensity. Time-resolved fluorescence measurements indicated that the latter is due to the formation of non-fluorescent porphyrin aggregates. The spectral characteristics of the porphyrin aggregates are discussed in terms of the formation of different types of aggregates. The location of the porphyrins within the bilayers was investigated by fluorescence quenching experiments using iodide, 9( 10)-bromooctadecanoic acid, and 16-bromohexadecanoic acid. These experiments suggest that THPP is located in the middle of the bilayer and TrHPyP near the aqueous interface. For the parent compound TPP no well-defined position was found. EPR spectroscopy on cast films of dioctadecyldimethylammonium surfactants with the copper derivatives of the porphyrins incorporated (porphyrin-to-surfactant ratio = 5 x 10~3) revealed a clear anisotropic distribution of the latter molecules in the cast bilayers. The angles between the porphyrin normals and the bilayer normal were determined by comparison of experiment with simulated spectra. In the case of THPP and TrHPyP these angles agree very well with an arrangement in which the long porphyrin axis lies parallel to the bilayer surface. The arrangement of TPP aggregates could not be established.