Ugo Cosentino

On the structure of polaronic defects in thiophene oligomers: a combined Hartree–Fock and Density Functional Theory study

Abstract Thiophene oligomer radical cations were studied as model for the polaronic defects in doped polythiophenes. Oligomers of increasing size (2 to 10 rings) were characterized by means of ab initio calculations. Optimized geometries and charge distributions were computed at both the Hartree–Fock (HF) and Density Functional Theory (DFT) levels. When electron correlation is taken into account the whole shape of the polaronic defect changes so that the self-localization of the positive charge and the corresponding quinoid structural distortion are greatly reduced. The energetics of the aromatic vs. quinoid geometry is investigated using substituted bithiophenes as model compounds. The discrepancy between HF and DFT results is confirmed. Traditional post-HF approach is found to agree with DFT.

NIR emitting ytterbium chelates for colourless luminescent solar concentrators

A new oxyiminopyrazole-based ytterbium chelate enables NIR emission upon UV excitation in colorless single layer luminescent solar concentrators for building integrated photovoltaics.

Modeling and prediction of molecular properties. Theory of Grid-Weighted Holistic Invariant Molecular (G-WHIM) descriptors

Abstract Recently proposed three-dimensional molecular indices (WHIM descriptors) have been used to search for quantitative structure-activity and structure-property relationships for several classes of compounds. WHIM descriptors contain information about the whole molecular structure in terms of size, shape, symmetry and atom distribution. These indices are calculated from the Cartesian coordinates of the atoms weighted in different manners and represent a very general approach to describe molecules in a unitary conceptual framework. In this paper the WHIM descriptor approach is extended to treat interaction scalar fields. The new G-WHIM (grid-weighted holistic invariant molecular) descriptors are calculated from the coordinates of the grid points where the field has been evaluated, each being weighted by the field value. The fields considered in the proposed example are related to non-bonding, electrostatic, and H-bonding interaction energies, evaluated by classical potentials. Two different sets of descriptors are obtained, for negative and positive potential values separately. The information contained in the whole grid is synthesized in a few parameters to be used in structure-activity relationship studies, thus avoiding difficulties related to chemical information spread out over a great number of grid points and thereby overcoming the problem of the dependence of the results upon molecule alignment. The interpretability of the results is quite evident and is defined by the same mathematical properties of the algorithm used for their calculation. The models obtained confirm the great modeling power of the G-WHIM descriptors.

Ab initio effective core potential calculations on lanthanide complexes: basis sets and electron correlation effects in the study of [Gd-(H2O)9]3+

Abstract Calculations on [Gd-(H 2 O) 9 ] 3+ at the restricted Hartree-Fock (RHF), density functional theory (DFT) and Moller- Plesset 2 (MP2) levels were performed using an effective core potential (ECP) including 4f electrons in the core for gadolinium. An optimized valence basis set with different contraction schemes for the metal, and the STO-3G, 3-21G, 6-31G ∗ , 6-31G ∗∗ and D95 ∗∗ basis sets for water molecules were used. Geometry optimization provided three main conformations: a minimum and two saddle points, each corresponding to a tricapped trigonal prism arrangement of the coordinated water molecules. The minimum energy conformation is of D 3 symmetry and does not correspond to any known experimental structure. The geometries of the two saddle points are of C 3 h and D 3 h symmetry, respectively, and correspond to two different crystallographic structures. At the DFT/D95 ∗∗ (RHF/D95 ∗∗ ) level these are respectively 4.95 (4.92) and 6.97 (6.26) kcal mol −1 above the global minimum. The results show that the major structural features of the coordination cage observed in the crystallographic structures are mainly due to intramolecular interactions between the coordinated water molecules. Intermolecular interactions, such as crystal packing forces and hydrogen-bond networks, should be responsible for the energy stabilization of the C 3 h and D 3 h structures in the solid state. At the RHF level, the STO-3G basis set is very sensitive to the choice of basis set on the metal center and, even in the best cases, provides unsatisfactory results. On the contrary, the 3-21G basis set provides, independently of the metal basis set, quite reliable geometries and conformational energies in qualitative agreement with those obtained using polarized basis sets. The results from the polarized basis sets themselves are consistent; further, inclusion of the electron correlation causes only a little shortening of the gadolinium-oxygen bond distances with respect to RHF and the conformational energies are substantially unaffected. These results highlight that calculations with the adopted ECP for the metal can provide reliable results in the study of gadolinium complexes also at the RHF level; further, a satisfactory representation of the potential energy surface of these systems can be obtained by 6-31G ∗ single point energy calculations on optimized 3-21G geometries.

The anti-fibrillogenic activity of tetracyclines on PrP 106-126: A 3D-QSAR study

There is evidence that Tetracyclines are potentially useful drugs to treat prion disease, the fatal neurodegenerative disease in which cellular prion proteins change in conformation to become a disease-specific species (PrPSc). Based on an in vitro anti-fibrillogenesis test, and using the peptide PrP106–126 in the presence of tetracycline and 14 derivatives, we carried out a three-dimensional quantitative structure-activity relationship (3D-QSAR) study to investigate the stereoelectronic features required for anti-fibrillogenic activity. A preliminary variable reduction technique was used to search for grid points where statistical indexes of interaction potential distributions present local maximum (or minimum) values. Variable selection genetic algorithms were then used to search for the best 3D-QSAR models. A 6-variable model showed the best predictability of the anti-fibrillogenic activity that highlighted the best tetracycline substitution patterns: hydroxyl group presence in positions 5 and 6, electrodonor substituents on the aromatic D-ring, alkylamine substituent at the amidic group in position 2 and non-epi configuration of the NMe2 group.

On the structure of bipolaronic defects in thiophene oligomers: a density functional study

The neutral and dication species of thiophene oligomers of increasing size (2 to 12 rings) have been examined and a study made of structural modifications occurring due to the increase in molecular charge; molecular properties such as charge-density distribution have been calculated. Preliminary results concerning the effect of electron correlation included at the density functional theory level are reported. Significant differences with respect to Hartree-Fock results are observed: the whole bipolaronic defect shape changes so that in the longer oligomers the bond-length alternation is no longer present.

A selected bibliography on PCDD and PCDF formation

Abstract A list of papers appeared in the worldwide literature in the period 1970-1987 is reported. The papers are classified according to a list of subjects which outlines the most significant aspects in the study of PCDD and PCDF formation.

Pharmacophore identification by molecular modeling and chemometrics: The case of HMG-CoA reductase inhibitors

SummaryA methodology based on molecular modeling and chemometrics is applied to identify the geometrical pharmacophore and the stereoelectronic requirements for the activity in a series of inhibitors of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme involved in cholesterol biosynthesis. These inhibitors present two common structural features—a 3,5-dihydroxy heptanoic acid which mimics the active portion of the natural substrate HMG-CoA and a lipophilic region which carries both polar and bulky groups. A total of 432 minimum energy conformations of 11 homologous compounds showing different levels of biological activity are calculated by the molecular mechanics MM2 method. Five atoms are selected as representatives of the relevant fragments of these compounds and three interatomic distances, selected among 10 by means of a Principal Component Analysis (PCA), are used to describe the three-dimensional disposition of these atoms. A cluster analysis procedure, performed on the whole set of conformations described by these three distances, allows the selection of one cluster whose centroid represents a geometrical model for the HMG-CoA reductase pharmacophore and the conformations included are candidates as binding conformations. To obtain a refinement of the geometrical model and to have a better insight into the requirements for the activity of these inhibitors, the Molecular Electrostatic Potential (MEP) distributions are determined by the MNDO semiempirical method.

Computational Investigation on the Spectroscopic Properties of Thiophene Based Europium β-Diketonate Complexes

The adiabatic transition energies from the lowest triplet states of four Europium tris β-diketonate/phenantroline complexes have been determined in vacuo and in dicholomethane solution by the ΔSCF approach at the density functional theory level, using the PBE1PBE and the CAM-B3LYP hybrid functionals. The calculated adiabatic transition energies have been compared with the experimental 0-0 transitions of each complex determined from phosphorescence spectra of the corresponding Gd(3+) complexes and followed by direct comparison between simulated and experimental spectra line shapes. For compound 1, the Eu(TTA)3Phen system, triplet states other than the lowest one and conformational isomers other than the one present in the crystallographic structure have been considered. In the crystallographic structure, this compound presents three quasi-degenerate low energy triplet states, differing for the TTA ligand where the two unpaired electrons are localized and showing close adiabatic transition energies. For compound 1, the lowest triplet states of the four investigated conformational isomers show similar characteristics and close adiabatic transition energies. On the basis of these results, an investigation of compounds 2-4 (Eu(Br-TTA)3Phen, Eu(DTDK)3Phen, and Eu(MeT-TTA)3) has been performed by considering only the isomer present in the crystallographic structure and only the lowest triplet state of each compound. For compounds 1-3, the energies of the lowest triplet states calculated by both functionals in solution including zero-point energy corrections well reproduce the experimental trends as well as the values of the adiabatic transition energies: CAM-B3LYP, the best performing functional, provides energies of the lowest triplet state with deviations from experiments lower than 1200 cm(-1). Also, the calculated vibrationally resolved phosphorescence spectra and UV-vis absorptions well reproduce the main features of their experimental counterparts. Significant differences between calculated and experimental results are observed for compound 4, for which difficulties in the experimental determination of the triplet state energy were encountered: our results show that the negligible photoluminescence quantum yield of this compound is due to the fact that the energy of the most stable triplet state is significantly lower than that of the resonance level of the Europium ion, and thus the energy transfer process is prevented. These results confirm the reliability of the adopted computational approach in calculating the energy of the lowest triplet state energy of these systems, a key parameter in the design of new ligands for lanthanide complexes presenting large photoluminescence quantum yields.

A combined use of global and local approaches in 3D-QSAR

Abstract A new methodology for 3D-QSAR studies, based on the combined use of global and local approaches, is proposed. Information on the whole molecular electrostatic potential distribution is obtained from a global approach and used to build global models, based on the grid weighted holistic invariant molecular (G-WHIM) descriptors, as well as to define an alignment criterion for developing local models. Moreover, a new technique based on local correlation indexes is proposed to perform the variable reduction. Both the global and the local models are obtained by a variable selection genetic algorithms technique. The methodology is applied to a benchmark steroid data set. The molecular electrostatic potential and the experimental binding affinity constants for the corticosteroid-binding globulin are used as variables. The QSAR models obtained compared with those obtained by the CoMFA method show higher predictive ability and give insight into the local molecular features that determine high binding affinity.