Alessandro Venturini

Ab initio MC-SCF study of thermal and photochemical [2 + 2] cycloadditions

The results of a study of few prototypical polar and non-polar [2 + 2] cycloadditions are presented at a level of theory where biradical and zwitterionic mechanisms can be treated in a balanced way (CAS-SCF). The polarity of the reactants is modelled either through the inclusion of donor/acceptor substituents (cycloaddition of dicyanoethene to hydroxyethene) or through the replacement of a carbon atom of the ethylenic CC double bond with a heteroatom (silaethene and formaldehyde). Two different types of reaction mechanism are documented in each case: (i) a two-step biradical mechanism and (ii) a concerted mechanism. The surface topology describing the two-step mechanism turns out to be almost independent of the polarity introduced by the substituents or by heteroatoms. In contrast, the topology of the surface describing the concerted mechanism is sensitive to substituents and heteroatoms. In non-polar systems (e.g. ethene dimerization) a concerted synchronous or asynchronous supra–supra pathway does not exist; however, in polarized π-systems we have been able to locate a true supra–supra transition state. Since this concerted transition state is at high energy, it will eventually become important only when solvent effects are considered.A study of the photochemical [2 + 2] dimerization occuring via the lowest excited singlet (S1) and triplet states (T1) is also presented. The computations demonstrate that the lowest-energy region of the S1 potential-energy surface is centered on a singularity (i.e. a cusp) corresponding to a conical intersection between the S1 and S0 surfaces. The presence of this topological feature seems to be related to the highly stereospecific formation of cyclobutane from simple 2,3-disubstituted alkenes.Both the change in potential surface topology on moving from non-polar to polar reactants and the nature of the excited-state decay process are rationalized using the same simple VB model.

Growth of p- and n-Dopable Films from Electrochemically Generated C60 Cations

The formidable electron-acceptor properties of C60 contrast with its difficult oxidations. Only recently it has become possible to achieve reversibility of more than one electrochemical anodic process versus the six reversible cathodic reductions. Here we exploit the reactivity of electrochemical oxidations of pure C60 to grow a film of high thermal and mechanical stability on the anode. The new material differs remarkably from its precursor since it conducts both electrons and holes. Its growth and properties are consistently characterized by a host of techniques that include atomic force microscopy (AFM), Raman and infrared spectroscopies, X-ray-photoelectron spectroscopy (XPS), secondary-ion mass spectrometry (SIMS), scanning electron microscopy and energy-dispersive X-ray analysis (SEM-EDX), matrix-assisted laser desorption/ionization (MALDI), and a variety of electrochemical measurements.

The existence and stability of singlet tetramethylene biradicals: an ab initio MCSCF/MP2 study

Abstract The formation and evolution of singlet tetramethylene biradicals that occur in the dimerization of ethylene to cyclobutane has been investigated using ab initio MCSCF and MCSCF/MP2 methods with double-zeta and 6–31G* basis sets. Two minima, corresponding to a trans and gauche structure, have been located. In contrast with earlier studies, when the contribution of dynamic correlation is computed at the MP2 level, the fragmentation barriers associated with these two minima do not disappear. However when the zero-point vibrational energy corrections are taken into account, the region of the surface corresponding to the closure to cyclobutane becomes extremely flat and the gauche minimum disappears. These results seem to indicate that the tetramethylene biradical exists as a single species with a trans geometry. The MP2 results yield an activation barrier of 44.70 kcal/mol with the 6–31G* basis and 43.21 kcal/mol at the double-zeta level; the experimental value is 43.8 kcal/mol.

Modulating the thermostability of Endoglucanase I from Trichoderma reesei using computational approaches

In the last decades, effective cellulose degradation became a major point of interest due to the properties of cellulose as a renewable energy source and the widespread application of cellulases (the cellulose degrading enzymes) in many industrial processes. Effective bioconversion of lignocellulosic biomass into soluble sugars for ethanol production requires use of thermostable and highly active cellulases. The library of current cellulases includes enzymes that can work at acidic and neutral pH in a wide temperature range. However, only few cellulases are reported to be thermostable. In order to alleviate this, we have performed a hybrid approach for the thermostabilization of a key cellulase, Endoglucanase I (EGI) from Trichoderma reesei. We combined in silico and in vitro experiments to modulate the thermostability of EGI. Four different predictive algorithms were used to set up a library of mutations. Three thermostabilizer mutations (Q126F, K272F, Q274V) were selected and molecular dynamics simulations at room temperature and high temperatures were performed to analyze the effect of the mutations on enzyme structure and stability. The mutations were then introduced into the endoglucanase 1 gene, using site-directed mutagenesis, and the effect of the mutations on enzyme structure and stability were determined. MD simulations supported the fact that Q126F, K272F and Q274V mutations have a thermostabilizing effect on the protein structure. Experimental studies validated that all of the mutants exhibited higher thermostability compared with native EGI albeit with a decrease in specific activity.

Crossover of two power laws in the anomalous diffusion of a two lipid membrane

Molecular dynamics simulations of a bi-layer membrane made by the same number of 1-palmitoyl-2-oleoyl-glycero-3-phospho-ethanolamine and palmitoyl-oleoyl phosphatidylserine lipids reveal sub-diffusional motion, which presents a crossover between two different power laws. Fractional Brownian motion is the stochastic mechanism that governs the motion in both regimes. The location of the crossover point is justified with simple geometrical arguments and is due to the activation of the mechanism of circumrotation of lipids about each other.

Anilino-Substituted Multicyanobuta-1,3-diene Electron Acceptors: TICT Molecules with Accessible Conical Intersections

A theoretical investigation based on DFT, TD-DFT, and CASSCF/CASPT2 methods has been carried out to elucidate the photophysics of two anilino-substituted pentacyano- and tetracyanobuta-1,3-dienes (PCBD and TCBD, respectively). These molecules exhibit exceptional electron-accepting properties, but their effective use in multicomponent systems for photoinduced electron transfer is limited because they undergo ultrafast (∼1 ps) radiationless deactivation. We show that the lowest-energy excited states of these molecules have a twisted intramolecular charge-transfer character and deactivate to the ground state through energetically accessible conical intersections (CIs). The topology of the lowest-energy CI, analyzed with a linear interpolation of the two branching-space vectors (g and h), indicates it is a sloped CI, ultimately responsible for the ultrafast deactivation of this class of compounds.

Camptothecin and Thiocamptothecin: the Role of Sulfur in Shifting the Hydrolysis Equilibrium towards the Closed Lactone Form

Adverse effects have limited the clinical potential of 20‐(S)‐camptothecin (CPT) and led to a growing interest in the development of CPT analogues that exhibit less severe drawbacks, while maintaining their therapeutic activity. Recently, a thiopyridone isostere of CPT, 20‐(S)‐thiocamptothecin (TCPT), was developed that resulted more potent than the parent compound in H460, HT29 and IGROV‐1 cell lines. The improved activity of TCPT over CPT might be due to the greater stability of the lactone ring. Here, reversible hydrolysis to the ring‐open carboxylate forms of CPT and TCPT was studied by HPLC, both in the presence and absence of human serum albumin (HSA). The amount of TCPT that exists in the lactone form at equilibrium in buffer solution (24 h) was found to be significantly higher than CPT, and the same trend was observed in the presence of HSA. Specifically, HSA caused a shift in the hydrolysis equilibrium of TCPT towards the carboxylate form, but the proportion of lactone form remained higher than that observed for CPT under the same conditions, and also in the presence of a higher excess of the protein. The role of the sulfur atom in the stability of the open and closed lactone derivatives was investigated by theoretical calculations using stabilization energies and comparison between experimental and calculated absorption spectra. Our results suggest that, in aqueous solution, more ionic species (anionic and enolic forms) are present for TCPT. This study provides further insights into the effects of oxygen/sulfur replacement in the CPT pyridone ring.

An ab initio MC-SCF study of the solvent effects in polar and non-polar [2 + 2] cycloadditions

Abstract Solvent effects in non-polar and polar [2 + 2] cycloadditions are examined with MC-SCF methods, using the dimerization of ethylene as a prototype of non-polar cycloaddition and the reaction between dicyanoethylene and hydroxyethylene as a prototype of polar cycloaddition. The effect of the solvent has been included via the continuum model of Rivail. Solvent effects stabilize the gauche transition state relative to the anti transition state in the two-step mechanism. The concerted transition state remains very high in energy, even when solvent effects are considered.

A New Potent Inhibitor of Glycogen Phosphorylase Reveals the Basicity of the Catalytic Site

The design and synthesis of a glucose-based acridone derivative (GLAC), a potent inhibitor of glycogen phosphorylase (GP) are described. GLAC is the first inhibitor of glycogen phosphorylase, the electronic absorption properties of which are clearly distinguishable from those of the enzyme. This allows probing subtle interactions in the catalytic site. The GLAC absorption spectra, associated with X-ray crystallography and quantum chemistry calculations, reveal that part of the catalytic site of GP behaves as a highly basic environment in which GLAC exists as a bis-anion. This is explained by water-bridged hydrogen-bonding interactions with specific catalytic site residues.

An ab-initio SCF-MO study of the solvent effect in α-substituted carbanions

Abstract This study reports an investigation at an ab-initio SCF-MO level of a supermolecule which involves a carbanion ( − CH 2 -F), a counterion (Li + ) and a certain number of solvent molecules. It was found that only the solvation of the counterion is very large, while that of the carbanion is quite small. Thus we have considered solvent molecules only around the counterion; in particular, three water molecules and two methanol molecules, to simulate the effect of an ether, the solvent most commonly used in reactions involving carbanions. We have found that for this supermolecule two distinct minima exist; the one with the lowest energy shows the feature of a tight ion pair and the other those of a solvent-separated ion pair. It was also found that the geometry of the carbanion is almost the same in both ion pairs, and more similar to that of the isolated carbanion than to that of the H 2 CFLi species.