Metal-organic compounds: a new approach for drug discovery. N1-(4-methyl-2-pyridyl)-2,3,6-trimethoxybenzamide copper(II) complex as an inhibitor of human immunodeficiency virus 1 protease.

The use of metal-organic complexes is a potentially fruitful approach for the development of novel enzyme inhibitors. They hold the attractive promise of forming stronger attachments with the target by combining the co-ordination ability of metals with the unique stereoelectronic properties of the ligand. We demonstrated that this approach can be successfully used to inhibit the protease of the human immunodeficiency virus (type 1). Several ligands bearing substituents designed to interact with the catalytic site of the enzyme when complexed to Cu(2+) were synthesised. The inhibition pattern of the resulting copper(II) complexes was analysed. We showed that the copper(II) complex of N1-(4-methyl-2-pyridyl)-2,3,6-trimethoxybenzamide (C1) interacts with the active site of the enzyme leading to competitive inhibition. On the other hand, N2-pyridine-amide ligands and oxazinane carboxamide ligand were found to be poor chelators of the cupric ion under the enzymatic assay conditions. In these cases, the observed inhibition was attributed to released cupric ions which react with cysteine residues on the surface of the protease. While unchelated metal cations are not likely to be useful agents, metal chelates such as C1 should be considered as promising lead compounds for the development of targeted drugs.

Photochemical electrocyclization of the indolinylphenylethenes involving a C-N bond formation.

[reaction: see text] A novel oxidative photodehydrocyclization of indolinylphenylethenes to a polycyclic heteroaromatic cation with good yields was described. Starting from the trans derivative, the phototransformation is a multistep process. The process includes two photochemical reactions and a trans-cis isomerization reaction, followed by an 1-aza-1,3,5-hexatrienic electrocyclic reaction involving the formation of a C-N bond. The cyclized product gives the stable heteroaromatic cations from hydride elimination with oxygen from air or iodine.

Solvatochromic behavior of donor-acceptor-polyenes: dimethylamino-cyano-diphenylbutadiene.

4-(Dimethylamino)-4'-cyano-1,4-diphenylbutadiene (DCB) and 4-(dimethylamino)-2,6-dimethyl-4'-cyano-1,4-diphenylbutadiene (DMDCB) have been characterized spectroscopically. Quantum chemical calculations were performed for comparison. Solvatochromic shifts of the fluorescence were strong and showed a linear dependence on the solvent polarity parameters, whereas shifts in the absorption spectra are very weak only correlate better with the polarizability of the solvents. Excited state dipole moments derived from fluorescence using the Onsager model are very large and similar for both compounds. It is concluded that a strongly allowed and highly dipolar pi, pi* state is the lowest excited state in polar solvents. The strong difference in absorption and fluorescence solvatochromic slopes suggests that the simple Onsager model with a point dipole approximation is not sufficient here.

Dual fluorescent polyaniline model compounds: steric and temperature effects on excited state charge separation.

Low temperature dual fluorescence of several derivatives of 4-aminodiphenylamine is investigated quantitatively. A strong thermochromic and solvatochromic redshift is indicative of the high dipole moment of the CT state emitting at long wavelength. The combination of steady state and time-resolved data allowed the calculation of the excited-state equilibrium. The absence of CT-risetimes in diethyl ether and their presence in butyronitrile points to the complication by additional ground state conformational equilibria. Both ground and excited state equilibria depend on solvent polarity and temperature. High solvent polarity favours one of the ground state conformers.

Photoswitching of cation complexation with A monoaza-crown dithienylethene photochrome.

A photochromic dithienylethene, bearing a phenyl azacrown as an ionophore and a formyl group as an electron-accepting substituent, changes its binding ability for Ca2+ by a factor higher than 103 by photoirradiation. This new photoionochromic displays a wavelength-dependent competition between fluorescence and photocyclization assigned to a red-shifted absorption of the fluorescing conformer compared to the absorption of the photoreactive conformer.

Tripodal ligand incorporating dual fluorescent ionophore: a coordinative control of photoinduced electron transfer.

p-(N,N-Dimethylamino)benzenesulfonamide (DMABSA), a dual fluorescent fluorophore, has been derivatized into two new fluoroionophores for transition metal cations. The electron-acceptor sulfonamide group has been N-substituted by a 2-pyridylmethylene group to lead to a bidentate ligand which forms a 2:1 complex with Cu(II). The crystal structure of the copper(II) complex is reported. The Cu(II) is coordinated through the pyridine N- and sulfonamide N-deprotonated atom which account for the blue-shift of the absorption and the partly quenched fluorescence. When DMABSA was incorporated into the tris(2-aminoethyl)amine (tren), a tripodal, dual-fluorescent ligand, is obtained which shows higher binding affinity for Zn(II) than for Cu(II). Furthermore, the large increase of the short wavelength emission and the disappearance of the TICT emission, upon Zn complexation, allow measurements of the Zn(II) concentration from relative fluorescence intensity at two wavelengths.

Structural modelling of optical and electrochemical properties of 4-aminodiphenylamines - optoelectronic studies on a polyaniline repeating unit.

Amino-diphenylanilines and their planarized and twisted model compounds have been investigated by steady state and time-resolved absorption and emission, as well as by spectroelectrochemistry. These polyaniline model compounds show that the observation of excited states with full charge separation is linked to molecular twisting where the diaminobenzene is the donor and the phenyl group the acceptor. The observable charge transfer fluorescence shows the characteristic features of twisted intramolecular charge transfer (TICT) excited states, i.e. forbidden emissive properties and strong solvatochromic red shift. The transient absorption spectrum of the TICT state matches the ground state absorption spectrum of the electrochemically produced radical cation of the molecule. This is the first example where excited-state properties of the neutral and ground state properties of the radical cation are directly linked.