Halide and hydroxide anion binding in water.

The formation of halide and hydroxide anion complexes with two ligands L1 (3,6-bis(morpholin-4-ylmethyl)-1,2,4,5-tetrazine) and L2 (3,6-bis(morpholin-4-ylethyl)-1,2,4,5-tetrazine) was studied in aqueous solution, by means of potentiometric and ITC procedures. In the solid state, HF2-, Cl- and Br- complexes of H2L22+ were analysed by single crystal XRD measurements. Further information on the latter was obtained with the use of density functional theory (DFT) calculations in combination with the polarizable continuum model (PCM). The presence of two halide or bifluoride HF2- (F-H-F-) anions forming anion-π interactions, respectively above and below the ligand tetrazine ring, is the leitmotiv of the [(H2L2)X2] (X = HF2, Cl, Br, I) complexes in the solid state, while hydrogen bonding between the anions and protonated morpholine ligand groups contributes to strengthen the anion-ligand interaction, in particular in the case of Cl- and Br-. In contrast to the solid state, only the anion : ligand complexes of 1 : 1 stoichiometry were found in solution. The stability of these complexes displays the peculiar trend I- > F- > Br- > Cl- which was rationalized in terms of electrostatic, hydrogen bond, anion-π interactions and solvent effects. DFT calculations performed on [(H2L2)X]+ (X = F, Cl, Br, I) in PCM water suggested that the ligand assumes a U-shaped conformation to form one anion-π and two salt bridge interactions with the included anions and furnished structural information to interpret the solvation effects affecting complex formation. The formation of hydroxide anion complexes with neutral (not protonated) L1 and L2 molecules represents an unprecedented case in water. The stability of the [L(OH)]- (L = L1, L2) complexes is comparable to or higher than the stability of halide complexes with protonated ligand molecules, their formation being promoted by largely favourable enthalpic contributions that prevail over unfavourable entropic changes.

Probing the molecular and electronic structure of capsaicin: a spectroscopic and quantum mechanical study.

The conformational preferences of capsaicin were investigated by using the hybrid meta density functional theory (DFT) method MPWB1K. Its flexible, pendant side chain allows for a multitude of conformations only slightly different in energy. The distinctive vibrational features of the most stable conformers were characterized. To elucidate the most favorable reaction sites of capsaicin for radical scavenging, various homolytic bond-dissociation energies were also calculated. Of the possible radical intermediates, the allyl and benzyl radicals are energetically preferred. The filled and empty electronic structures of capsaicin were investigated by exploiting the photoelectron and electron-transmission spectra also of reference molecules and suitable quantum-mechanical calculations. On this basis, a reliable pattern of the vertical ionization energies and electron-attachment energies of capsaicin was proposed. The frontier pi molecular orbitals are concentrated over the vanillyl moiety, with a modest influence of the amidic-aliphatic chain. The (negative) first vertical electron affinity is predicted to be similar to that of benzene. The absorption spectrum of capsaicin and its change by conversion into a phenolic deprotonated anion (modest bathochromic displacement) or a phenoxyl neutral radical (from colorless to red) were interpreted with time-dependent DFT calculations. ESR measurements following chemical or electrochemical reduction of capsaicin did not lead to detection of the corresponding radical anion. The spectra show fragmentation of the original molecule and formation of a variety of radical species which are believed to have a semiquinonic structure.

Spectroscopic and theoretical study of the electronic structure of curcumin and related fragment molecules.

The low volatility and thermal instability made the photoelectron (PE), electron transmission (ET), and dissociative electron attachment (DEA) spectroscopy measurements on curcumin (a potent chemopreventive agent) unsuccessful. The filled and empty electronic structure of curcumin was therefore investigated by exploiting the PES, ETS, and DEAS results for representative fragment molecules and suitable quantum-mechanical calculations. On this basis, a reliable pattern of the vertical ionization energies and electron attachment energies of curcumin was proposed. The pi frontier molecular orbitals (MOs) are characterized by sizable interaction between the two phenol rings transmitted through the dicarbonyl chain and associated with a remarkably low ionization energy and a negative electron attachment energy (i.e., a largely positive electron affinity), diagnostic of a stable anion state not observable in ETS. The lowest energy electronic transitions of half-curcumin and curcumin and their color change by alkalization were interpreted with time-dependent density functional theory (DFT) calculations. For curcumin, it is shown that loss of a phenolic proton occurs in alkaline ethanolic solution.

Evaluation of free energy landscape for base-amino acid interactions using ab initio force field and extensive sampling.

Structural data of protein-DNA complex show redundancy and flexibility in base-amino acid interactions. To understand the origin of the specificity in protein-DNA recognition, we calculated the interaction free energy, enthalpy, entropy, and minimum energy maps for AT-Asn, GC-Asn, AT-Ser, and GC-Ser by means of a set of ab initio force field with extensive conformational sampling. We found that the most preferable interactions in these pairs are stabilized by hydrogen bonding, and are mainly enthalpy driven. However, minima in the free energy maps are not necessarily the same as those in the minimum energy map or enthalpy maps, due to the entropic effect. The effect of entropy is particularly important in the case of GC-Asn. Experimentally observed structures of base-amino acid interactions are within preferable regions in the calculated free energy maps, where there are many different interaction configurations with similar energy. The full geometry optimization procedure using ab initio molecular orbital method was applied to get the optimal interaction geometries for AT-Asn, GC-Asn, AT-Ser, and GC-Ser. We found that there are various base-amino acid combinations with similar interaction energies. These results suggest that the redundancy and conformational flexibility in the base-amino acid interactions play an important role in the protein-DNA recognition.

Quinolone derivatives: synthesis and binding evaluation on cholecystokinin receptors.

A series of 1,2-dihydro-4-phenylquinolin-2-one-3-carboxylic acid and of 3-amino-4-phenylcarbostyril derivatives were synthesized and examined for their CCK receptor affinities. These compounds displayed micromolar affinities for CCK-A rather than CCK-B receptor and the results have been discussed on the basis of a molecular modelling study.