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Circular dichroism (CD) spectra of non-covalent ligand : biomolecule couples contain information on the equilibrium geometries of the associated structures that can be retrieved upon comparison of the sign and intensity of the experimental CD bands with the quantum mechanically calculated rotational strengths of low energy supramolecular complexes, obtained from molecular modelling methods. For both chiral and achiral ligands this approach proved useful to reach a structure based rationale of ground and excited state properties of the non-covalent ligand : protein associates. In this Perspective we illustrate the potential of this method focusing on the main achievements of our recent spectroscopic, conformational and photochemical studies on drug-albumin complexes and collocate it in the frame of current methodologies of molecular modelling and spectroscopic investigation of ligand : biomolecule binding.

Energy transfer in a series of hetero-dyads of zinc porphyrin and free-base porphyrin connected at the beta position by pi conjugated bridges has been determined. The dyads have been characterized and compared with the homo dyads, excellent models for the donor and the acceptor porphyrins in the electronically conjugated system. The homo dyads provide reliable parameters for the determination of the energy transfer rate calculated according to the Förster theory. This model was inadequate to account for the experimental findings and an electron exchange mechanism was shown to contribute. A favorable coplanar arrangement of the bridge and the tetrapyrroles facilitates the energy transfer process, which displays a very low distance dependence and an efficiency >98%.

A combined approach using global analysis of circular dichroism multiwavelength data and time resolved fluorescence was applied to investigate the interaction of R-(-)- and S-(+)-ketoprofen with bovine serum albumin in buffer solution at neutral pH. A characterization of the most stable drug : protein adducts of 1 : 1 and 2 : 1 stoichiometry, as individual chemical species, was obtained. The stability constants and the absolute circular dichroism spectra of the diastereomeric complexes were determined. The spectra of the 1 : 1 conjugates are opposite in sign, those of the 2 : 1 complexes are both negative, but different in shape from each other (peaks at 358 and 342 nm for S-(+)- and R-(-)-ketoprofen, respectively). A tryptophan residue was shown to be involved in the binding of the drug, in the primary site for the R-(-) and in the secondary site for the S-(+) enantiomer, thereby showing that chiral recognition by the protein causes the site of highest affinity being not the same for both optical antipodes.

A series of triphenylamine (TPA) based compounds is investigated by means of density functional theory and cyclic voltammetry. Using the Nicholson's formalism, the measured deltaE(p) are correlated with B3LYP/6-31G* calculated reorganisation energies (lambda), elucidating the trend followed by the electron transfer rate of these compounds. Besides the direct dependency upon the dimension of the cationic fragment contributing to the hole stabilisation, the lambdas are tuned by the symmetry local to the TPA units, as evidenced by the structural relaxation of the cations. MDTAB shows the interesting combination of low ionisation potential (IP) and low lambda. This can make this compound interesting for practical applications in organic light emitting diode (OLEDs) devices, due to the direct correlation of the IP and lambda with the hole transfer efficiency to the anode, along with the hole mobility.