Replacing the ammonium polar head in cationic lipids 1 (A=N) by a phosphonium or an arsonium group (A=P, As) improves their properties as synthetic vectors for DNA transfection. The increased volume of the cationic head is supposed to modify the interactions of the vector with the solvent and DNA.

Replacing the ammonium polar head in cationic lipids 1 (A=N) by a phosphonium or an arsonium group (A=P, As) improves their properties as synthetic vectors for DNA transfection. The increased volume of the cationic head is supposed to modify the interactions of the vector with the solvent and DNA.

A series of ferrocenyl conjugates to fatty acids have been designed and synthesized to establish the key properties required for use in biomolecular binding studies. Amperometric detection of the ferrocene conjugates was sought in the region of 0.3 V (vs Ag/AgCl) for use in protein/blood solutions. Different linkers and solubilizing moieties were incorporated to produce a conjugate with optimal electrochemical properties. In electrochemical studies, the linker directly attached to the ferrocene was found to affect significantly the E(1/2) value and the stability of the ferrocenium cation. Ester-linked ferrocene conjugates had E(1/2) ranging from +400 to +410 mV, while amide-linked compounds ranged from +350 to +370 mV and the amines +260 to +270 mV. Folding of long-chain substituents around the ferrocene, also significantly affected by the choice of linker, was inferred as a secondary effect that increased E(1/2). The stability of the ferrocenium cation decreased systematically as E(1/2) increased. Disubstituted ferrocene ester and amide conjugates, with oxidation potentials of +640 and +570 mV, respectively, showed only a barely discernible reduction wave in cyclic voltammetry at 50 mV/s. Electrochemical measurements identified two lead compounds with the common structural characteristics of an amide and carbamate linker (compounds 17 and 21) with a C(11) fatty acid chain attached. It is envisaged that such molecules can be used to mimic and study the biomolecular binding interaction between fatty acids and molecules such as human serum albumin.

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Methodologies to access water soluble large ringed calixarenes in good yield using efficient synthetic procedures have been investigated. Symmetrical partial functionalisations at the lower rim are described using activated [n]ethylene glycol chains and the addition behaviour contrasted with that of bromoalkanenitriles which proceeds with no observed regioselectivity. Full functionalisations of the calixarenes bearing hydrophilic groups are then investigated and a two-step procedure established which appears to be generally applicable for the addition of different [n]ethylene glycol chains. Furthermore, difunctionalisation under different reaction conditions are described. Throughout, strategies for the characterisation of these high mass compounds are outlined.

Durch Ersetzen der polaren Ammoniumgruppe in kationischen Lipiden 1 (A=N) durch eine Phosphonium‐ oder eine Arsoniumgruppe (A=P, As) wird die Fähigkeit dieser Lipide, als synthetische Vektoren für die DNA‐Transfektion zu dienen, deutlich verbessert. Das vergrößerte Volumen der kationischen Kopfgruppe beeinflusst dabei die Wechselwirkungen des Vektors mit dem Lösungsmittel und der DNA.

The development of electrochemical probes useful for investigating the occupancy by other molecules of sites on complex proteins such as human serum albumin (HSA) is described. Ferrocenyl-(oxoethylene)-fatty acid compounds of different fatty acid chain length probed different binding sites on HSA. The interaction could be changed from one primarily with a drug binding site, when the probe was ferrocene methanol, to one predominantly with medium-chain fatty acid binding sites, by adding an (oxoethylene)-fatty acid substituents. Finally, the interaction could be changed to one interacting primarily with high-affinity long-chain fatty acid binding sites, as the fatty acid chain length in ferrocene-(oxoethylene)-fatty acid molecules increased. These results strongly implied that the binding could be further tailored by relatively simple modifications to the probe, for example, by changing the balance of hydrophobicity and hydrophilicity. The possibility of a procedure using mass-produced electrochemical cells to determine the fractional occupancy of different sites on HSA is demonstrated.