(PER.1) A realistic potential model for the study of the solvation of N-methylacetamide water system using molecular dynamics simulations

Prof. Antonio Laganà and Dr. Noelia Faginas Lago

The role played by water in influencing structure and functions of biological macromolecules is not yet completely understood. A way of improving our understanding of these mechanisms is to carry out Molecular Dynamics (MD) studies of the processes leading to the solvation of biological macromolecules in water. This is indeed the goal of the proposed bachelor thesis that deals with the extension of a previous MD study of the effect of diluting a water solution of the N-methylacetamide (NMA). In particular the investigation is aimed at analyzing how the structure of hydrogen bonds of the system water-NMA (which are known to stabilize polypeptide secondary structures) vary with the dilution of the system.

The MD study will focus on the following two important limiting cases:

a.) diluted NMA in which the hydration of the peptide group leads to specific structures of the hydrogen-bonded oligomers in aqueous solution.

b.) concentrated NMA in which water fills the interstitial space of an environment rich in peptide groups.

The MD simulations will be carried out using the DL_POLY package and two recent formulations of the related force field (a new bond-bond and an AMPF force field for the NMA and water, respectively). Out of the results of the MD simulations it will be possible to calculate the radial distribution functions (RDF), the chemical shifts and the shape of the hydrogen bonds networks.

(PER. 2) Synthesis of hybrid organic-inorganic nanoparticles with controlled photochemical behaviour

Prof. Loredana Latterini

Hybrid organic-inorganic nanostructures having a defined morphology and structure controlled at nanometric level with functions which can be optically activated represent a new and interesting class of materials with potential applications in electronic and optoelectronic materials, in controlled drug release, and for diagnostic and therapeutic purposes. The controlled entrapment of organic chromophores/fluorophores in semiconductor (SiO2, TiO2, ZnO, etc.) nanoparticles can lead to an increase of their photostability and emission intensity (brightness) with respect to the free molecules or to control the photochemical reactivity of the chromophore. Such improved performances result from the prevention or reduction of quenching phenomena, the loss of degree of freedom and the confinement of defined molecular configurations in nanospace.

Among various processes to synthesize nanomaterials, sol-gel method appears to be one of the most versatile and cost-effective process for producing nanomaterials in various shapes and forms. Changing the structure of precursors affects the porosity of the nanomaterials and thus the density of the inorganic nanomatrix. Chromophore-doped semiconductor nanoparticles can be achieved by entrapping the organic photoactive molecules or by covalently conjugating the dye to one of the precursors. The possibility to easily change the preparation conditions enables inflection of the arrangement of the chromophore molecules in the nanoparticles thus tuning their photophysical and photochemical behavior.

The project involves the development of methods for the preparation of dye-doped semiconductor nanoparticles with designed porosity and their characterization using optical, electron, and scanning probe microscopy, as well as different spectroscopic techniques. Then the photochemical behavior of the entrapped dye is carried out and the results used to modify the preparation procedure in order to achieve a full control over the optical response of the material (fluorescence enhancement, electron transfer, photoisomerization, photochromism, etc.).

The summer program may be broken down into many small projects involving different techniques. Participants may choose from various simple projects related to synthesis and characterization of nanoparticles, including the more sophisticated procedures to use the photoinduced reaction to optically modify the nanoparticle surface chemistry.

(PER. 3) Advanced NMR Studies on Metallorganic Catalysts: Understanding Supramolecular Structure/Reactivity Relationships

Prof. Alceo Macchioni

Our research focuses on the intra and intermolecular characterization of metallorganic catalysts through advanced NMR techniques. In particular, innovative methodologies have been developed for the determination of the interionic structure of organometallic salts exploiting the complementarity of information deriving from NOE (Nuclear Overhauser Effect) (Macchioni, A. Eur. J. Inorg. Chem. 2003 , 195) and PGSE (Pulsed Field Gradient Spin-Echo) (Macchioni, A. et al. Chem. Soc Rev., 2008, 37, 479) NMR techniques. PGSE experiments are used to determine the relative orientation of ionic fragments while NOE experiments allow the average hydrodynamic size of ionic species to be evaluated. In recent years, we have studied catalyst precursors for (i) CO/olefin copolimerization reactions (Binotti, B. et al. Chem. Eur. J., 2007.13, 1570), (ii) hydrogenation reactions by hydrogen transfer to ketones (Zuccaccia, D. et al. Organometallics, 2007, 26, 3930) (iii) the polymerization of olefins (Rocchigiani, L. et al. Chem. Eur J. 2008, 14, 6589) and (iv) catalytic gold (I) systems (Zuccaccia, D. et al. J. Am. Chem. Soc 2009, 131, 3170).

Summer projects for undergraduates will involve the synthesis and characterization of metallorganic complexes belonging to one of the (i)-(iv) classes. In the course of their research projects, students will learn how to handle air-sensitive compounds and advance NMR techniques.

(PER. 4) Ab-initio study of water’s intermolecular interactions

Prof. Francesco Tarantelli

While the interaction energy surfaces of water with a large number of other chemical systems have been extensively and accurately studied, very little still is known about the very nature of these non-covalent interactions beyond standard van-der-Waals models. As a result, while water is the most ubiquitous and arguably the most important chemical species for the sustainment of life on earth, there are still severe limits to our understanding of hydrogen bonding, of solvation, and of other important interactions of atmospheric chemistry. We propose to use our recently introduced theoretical analysis of the electron charge displacement taking place upon formation of a chemical interaction to obtain useful and detailed information on the nature of intermolecular forces. A wide choice of molecular complexes, typically of small to medium size will be studied. In particular, we focus on the role played by charge-transfer components and attempt to explain the marked directionality which appears to be so peculiar of water’s interactions. The electron density studied in these investigations is obtained by the most accurate quantum-chemical methods available today. As previous experience has shown, due to the small size of the molecules studied and the high degree of modularity of the project, some of these investigations are ideally suited to be carried out in few weeks. The subject matter is of basic, general appeal, and oriented towards the illustration of fundamental aspects of chemical bonding. The visiting student will be gradually exposed to the underlying theoretical models and rapidly enabled to carry out calculations in autonomy, using the most popular ab-initio programs.

(PER. 5) Polymer-supported organocatalysts as efficient tools for the definition of novel green synthesis of target molecules

Dr. Luigi Vaccaro

Currently, in the Green Synthetic Organic Chemistry group of the Università di Perugia the research is aimed at the development of new solid catalytic systems with the intention of optimizing synthetic processes both from the chemical and environmental point of views. Catalytic systems are specifically designed to achieve the highest efficiency when used in the presence of environmentally-friendly reaction media (http://www.fda.gov/cder/guidance/index.htm) or under solvent-free conditions. In addition, our investigations intend to define the role of the solid support in the optimization of cyclic continuous-flow reactors (automated synthesis) facilitating or not the recovery and reuse of the catalysts and the minimization of the organic solvent needed for the isolation of the final product. Attention is further focused on the definition of green processes for the preparation of target molecules.Interesting studies have reported on how the molecular features of solid support influences the "swelling" process, through which the organic solvent soaks the polymeric matrix and swells it, allowing or not the facile access of the reagents to the catalytic sites. We plan to follow two main directions to increase the efficiency of solid organocatalysts:

a.) Increase the space between the polystyrene network by using polymers known as "Janda Jel", where the cross-linker is a 1-(4'-phenoxybutoxy)benzene. This should ensure a higher accessibility of the reactants to the catalytic sites.

b.) Increase the loading by increasing the number of functionalizable sites allowing a higher reactants/catalyst ratio by using Rasta resins. In fact this type of polymers typically feature a high loading capacity and posses a molecular architecture that should make easier the approach of reactants to the catalytic sites.

The novel catalytic systems will be used to promote fundamental organic transformations mainly focusing on carbon-carbon bond forming processes. As an example, an on-going project involves a novel green procedure for the synthesis of Warfarin and its derivatives. Sold as Coumadin by Bristol-Myers Squibb, it is one of the two world best-selling antithrombotic drug. Together with Plavix by Sanofi-Aventis, it represents around 700 million dollars per year, with a synthesis based on the Michael addition of active methylenes on alpha-beta-unsaturated compounds.

Undergraduate students can participate in this research by choosing small projects concerning the catalyst preparation, the reaction condition optimization or the scale-up process for the set-up of a continuous-flow reactor and the definition of an automated protocol.