Demetrio Pitea

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.

Kinetics of biodegradation of mixtures containing 2,4-dichlorophenol in a continuous stirred reactor

A solution containing 2,4-dichlorophenol (DCP) and phenol (or glucose), in the ratio 1:1 in terms of carbon, was fed to a completely mixed continuous flow reactor with recycle and controlled wasting of the activated sludge, operated at steady-state conditions at 20°C. A carefully adapted sludge was able to degrade DCP, besides the accompanying substrate, with no evidence of substrate inhibition in the concentration range covered (156 mg l−1 in the influent). The reactivity order was found to be glucose ⪢ phenol > DCP. The results of a series of kinetic runs with phenol + DCP were interpreted by a first-order equation for phenol and by the Monod model for DCP.

A hypothesis on the mechanism of PCDD biological activity based on molecular electrostatic potential modeling. Part 2

We have focused our attention on the electrostatic properties of a set of PCDDs, polychlorinated dibenzo-p-dioxins, of known binding affinities for the Ah receptor. In this paper we analyze the molecular electrostatic potential (MEP) of the six selected isomers, 2,3,6-TrCDD, 1,2,4,7,8-PeCDD, 1,2,3,4-TCDD, 1,2,3,4,7-PeCDD, 1,2,4-TrCDD and 1-MCDD, in order to validate the results previously obtained on a test set of eight PCDDs. A visual analysis of the MEP distributions shows that the stepwise differentiation from the electrostatic characteristics typical of the most active isomers is associated with a decrease in binding affinity; however, the simultaneous occurrence of different trends for different electrostatic requirements for activity does not make for a simple definition of the relationships between MEP patterns and affinities for the whole set of isomers. The information retained in the overall MEP distributions is summed up in a few carefully chosen descriptors, i.e. the MEP values in particular points located around the molecules. A statistical analysis performed by linear and non-linear methods elucidates the electrostatic requirements effective in the recognition process with the Ah receptor; from this there also emerges a physical interpretation of the process. In particular, two different types of electrostatic feature associated with two subsets of PCDD isomers appear to be recognized by the Ah receptor.

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.

Degradation of Octachlorodibenzofuran and Octachlorodibenzo-p-dioxin Spiked on Fly Ash: Kinetics and Mechanism.

Octachlorodibenzofuran (OCDF) degradation kinetics in a moist nitrogen stream and those of octachlorodibenzo-p-dioxin (OCDD) in a dry or moist airstream on pretreated fly ash were studied in a laboratory pilot plant with temperature ranging from 200 to 350 °C and reaction times varying from 15 to 240 min. The mathematical treatment of experimental data indicated that two reaction pathways, decomposition and dechlorination, operated independently because of a partition of the reagents in the fly ash according to a physical and a chemical adsorption. The decomposition reaction was of the first order with respect to the reactant adsorbed physically. The dechlorination reaction involved first-order series reactions. Here, the kinetic scheme for the first two dechlorination steps is discussed. Kinetic constants and partition constants at different temperatures as well as Arrhenius and Eyring parameters and the isosteric enthalpy of adsorption are calculated.

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.