Giuseppe M. Lombardo

Modeling vacancies and hydrogen impurities in graphene: A molecular point of view

Abstract We have followed a ‘molecular’ approach to study impurity effects in graphene. This is thought as the limiting case of an infinitely large cluster of benzene rings. Therefore, we study several carbon clusters, with increasing size, from phenalene, including three benzene rings, up to coronene 61, with 61 benzene rings. The impurities considered were a chemisorbed H atom, a vacancy, and a substitutional proton. We performed HF and UHF calculations using the STO-3G basis set. With increasing cluster size in the absence of impurities, we find a decreasing energy gap, here defined as the HOMO–LUMO difference. In the case of H chemisorption or a vacancy, the gap does not decrease appreciably, whereas it is substantially reduced in the case of a substitutional proton. The presence of an impurity invariably induces an increase of the density of states near the HOMO level. We find a zero mode only in the case of a substitutional proton. In agreement with experiments, we find that both the chemisorbed H, the substitutional proton, and the C atom near a vacancy acquire a magnetic moment. The relevance of graphene clusters for the design of novel electronic devices is also discussed.

High field NMR techniques, molecular modelling and molecular dynamics simulations in the study of the inclusion complex of the cognition activator (±)-1-(4-methoxybenzoyl)-5-oxo-2-pyrrolidinepropanoic acid (CI-933) with β-cyclodextrin

Abstract The formation of the inclusion complex of β-cyclodextrin with the new cognition activator (±)-1-(4-methoxybenzoyl)-5-oxo-2-pyrrolidinepropanoic acid (CI-933) and the chiral discrimination capability of the macrocyclic host towards the racemic guest were evident from 1H NMR studies. The structure, relative host-guest orientation and binding mode of the complex were studied using the ROESY NMR technique complemented by molecular modelling and molecular dynamics simulations ( charmm ). All these methods converged towards the structure attained by inserting the guest, the aromatic ring first, into the hydrophobic cavity of the host from the side of the secondary hydroxyls. Both the R- and S-enantiomers were found deeply inserted into the host, the diastereoisomeric complexes formed featuring different numbers and distribution of intermolecular hydrogen bonds.

High‐field NMR spectroscopic techniques combined with molecular dynamics simulations for the study of the inclusion complexes of α‐ and β‐cyclodextrins with the cognition activator 3‐phenoxypyridine sulphate (CI‐844)

The formation of complexes and the mode of binding to macrocyclic host molecules (α‐ and β‐cyclodextrins, CDs) of the nootropic drug CI‐844 (3‐phenoxypyridine sulphate, Warner‐Lambert/Parke‐Davis) were studied using NMR techniques (T‐ROESY) complemented by molecular dynamics (MD) protocols which allowed complete interpretation of the NMR experimental data. The NMR experiments indicated that a 1:1 stoichiometry of the complexes exists and revealed dipolar contacts between selected protons of the guest and inner protons of the hosts. The NMR data suggest the same relative host–guest alignment in the complexes, but that the guest has different mobilities in the complexes formed. The MD simulations in the gas phase gave a first rough indication of the structure of each complex. The MD simulations with explicit water molecules reproduced the experimental sets of 1H–1H contacts and thus provided reliable information on the relative host–guest alignments and geometries of the complexes. In the β‐Cd complex the CI‐844 molecule penetrates deeply into the cavity from the larger rim side with the phenyl‐group moiety. An analogous relative host–guest alignment as in the β‐CD complex was found in the α‐CD complex. In this latter case the CI‐844 is not deeply embedded into the host’s cavity, and the guest fluctuates widely about the equilibrium position, thus denoting lower stability of the α‐CD–CI‐844 complex with respect to the β‐CD–CI‐844 complex. The use of β‐CD as host is therefore adequate for vehiculation of the drug. The relative hydrophobic–hydrophilic energetics of the phenyl and pyridinium rings of CI‐844 were the factor determining the orientation of the guest in the inclusion process. The study also confirmed the importance of including explicitly the solvent molecules in the simulations of ionic systems in order to interpret correctly the experimental data and the location of the host–guest contact distances falling within 3.5 Å (NOE effective) and their fluctuations.

1/Z expansion, correlation energy, and Shannon entropy of heavy atoms in nonrelativistic limit

It has been known since the work of March and White that the simplest nonrelativistic density functional theory, namely, the statistical method of Thomas, Fermi, and Dirac, sums subseries of the so-called 1/Z expansion to yield, for heavy neutral atoms, the ground-state energy E= − a0Z7/3+ a1Z2−a2Z5/3+⋅⋅⋅. The term of O(Z5/3) is the Dirac–Slater exchange energy Eexc, and it is of considerable interest to know at what order the correlation energy Ecorr enters this expansion. Dimensional scaling considerations by Kais et al. suggested Ecorr∝Z4/3 in the limit of large Z. Here, attention is focused on whether this can be distinguished empirically from a term of the form (aZu2009lnu2009Z+bZ) for neutral atoms. If the latter term is correct, then a relationship between Ecorr and the Shannon information entropy can be forged analytically for large atomic number Z in nonrelativistic theory.xa0© 1998 John Wiley & Sons, Inc. Int J Quant Chem 69: 721–726 (1998)

NMR spectroscopic evidence and molecular dynamics studies on inclusion and non-inclusion phenomena between β-cyclodextrin and new anti-Alzheimer's drugs tacrine (CI-970), velnacrine (HP-029) and suronacrine (HP-128)

The formation of supramolecular complexes of β-CD with new generation anti-Alzheimers agents of the 1,2,3,4-tetrahydro-9-aminoacridine family (tacrine hydrochloride, 1, velnacrine maleate, 2 and suronacrine maleate, 3), has been studied using molecular dynamics (MD) simulations both in vacuo and with a water sphere. High-field NMR experiments for 1 and 2 gave experimental evidence of their effective non-inclusion. However, earlier NMR studies demonstrated inclusion of 3 on the basis of the observed upfield shifts of the 3-H and 5-H protons of the β-CD cavity.MD calculations performed for molecules in vacuo gave uncertain results that evidenced failure of this model to reproduce consistently the set of the three experiments. Such a failure was overcome by including explicitly water molecules in the model, thus showing that an oversimplified model for modelling complexes of charged molecules is susceptible to incorrect conclusions.The calculations performed for cations 1, 2 and 3 in the water sphere also showed that 1 and 2 are more hydrophilic than 3. This suggests that the relative strength of the solvation and of the complex formation constants favours complexation of 3 instead of its non-inclusion, and vice versa in the cases of 1 and 2.An important general aspect of β-CD supramolecular complexes of charged species was found to be controlled by the solvation effects that must be necessarily included to correctly model, in the absence of safe experimental information like that coming from NMR, inclusion or non-inclusion of a guest into the host.

Experimental and in silico characterization of a biologically active inosose

Inositols have been recently reported to show a biological activity as inhibitors of both glycosidase and amyloid-β protein. After having harvested good crystals suitable for single crystal X-ray diffraction, we performed a comparison with the data inferred by means of a molecular dynamics simulation, based on the use of an appropriate Force Field coupled to the most performing charging scheme. This approach allowed a detailed analysis extended to ultra-fine details, such as atomic displacement parameters. It confirmed the good validity of a robust approach already tested by us in previous studies. A NMR analysis of the molecule in solution was also carried out, to compare the structural findings suggested by the X-ray analysis with the ones in solution and avoid confining them to the solid-state. In this framework, we investigated the above-mentioned inhibiting activity of a class of inososes, by means of a molecular docking investigation, which proved the suggested validity of the studied compound as inhibitor of the α-glucosidase.

Potassium caffeate/caffeic acid co-crystal: the rat race between the catecholic and carboxylic moieties in an atypical co-crystal†

The vast literature concerning caffeic acid and its derivatives lacks any reference to the solid state structures of its inorganic salts as these crystals are quite difficult grow. Most of the already published works deal with computational studies of these compounds as well as investigations of their behaviour in solution. Having obtained good quality potassium caffeate/caffeic acid co-crystals, we solved their structure and used a robust approach, already applied to caffeic acid alone, to compare the X-ray structure with the one inferred by Molecular Dynamics (MD), focusing our attention on the structure-property relationships. The reliability of this method is confirmed by the overall agreement extended up to the anisotropic displacement parameters calculated, on one hand, by means of MD and the ones gathered, on the other hand, by X-ray measurements. Moreover, the lack of experimental evidence of an enthalpically favored polymorph, arising from the MD calculations, were explained on the basis of the Shannons entropy.

Correlation energies in polyatomic molecules modelled in terms of bond order

Earlier work has used the concepts of density functional theory to achieve useful estimates of both atomic and diatomic molecular correlation energies. In the present work, some of these ideas are combined with more conventional chemical ideas relating to bond order to evaluate correlation energies in some thirty polyatomic molecules. There are a number of empirical parameters in the present modelling process, but once these are fixed on some 16 molecules the correlation energies in the remaining molecules follow quantitatively, without any adjustments.

A top-down approach to crystal engineering of a racemic Δ2-isoxazoline.

The crystal structure of racemic dimethyl (4RS,5RS)-3-(4-nitrophenyl)-4,5-dihydroisoxazole-4,5-dicarboxylate, C13H12N2O7, has been determined by single-crystal X-ray diffraction. By analysing the degree of growth of the morphologically important crystal faces, a ranking of the most relevant non-covalent interactions determining the crystal structure can be inferred. The morphological information is considered with an approach opposite to the conventional one: instead of searching inside the structure for the potential key interactions and using them to calculate the crystal habit, the observed crystal morphology is used to define the preferential lines of growth of the crystal, and then this information is interpreted by means of density functional theory (DFT) calculations. Comparison with the X-ray structure confirms the validity of the strategy, thus suggesting this top-down approach to be a useful tool for crystal engineering.

Equilibrium geometries of low-lying isomers of some Li clusters, within Hartree-Fock theory plus bond order or MP2 correlation corrections

In a recent study by Kornath et al. [J. Chem. Phys. 118, 6957 (2003)], the Li(n) clusters with n=2, 4, and 8 have been isolated in argon matrices at 15 K and characterized by Raman spectroscopy. This has prompted us to carry out a theoretical study on such clusters up to n=10, using Hartree-Fock theory, plus low-order Møller-Plesset perturbation corrections. To check against the above study of Kornath et al., as a by-product we have made the same approximations for n=6 and 8 as we have for n=10. This has led us to emphasize trends with n through the Li(n) clusters for (i) ground-state energy, (ii) HOMO-LUMO energy gap, (iii) dissociation energy, and (iv) Hartree-Fock eigenvalue sum. The role of electron correlation in distinguishing between low-lying isomers is plainly crucial, and will need a combination of experiment and theory to obtain decisive results such as that of Kornath et al. for Li(8). In particular, it is shown that Hartree-Fock theory plus bond order correlations does account for the experimentally observed symmetry T(d) symmetry for Li(8).