Daniele Padula

Diversonol and Blennolide Derivatives from the Endophytic Fungus Microdiplodia sp.: Absolute Configuration of Diversonol

Chemical investigation of the fungal strain Microdiplodia sp. isolated from the shrub Lycium intricatum led to the isolation of four new compounds: a hexahydroxanthone (2), a 2,3-dihydrochroman-4-one (3), a 7-oxoxanthone derivative (4), and a 1,4-oxazepan-7-one (5). The relative configurations of the new compounds were determined by intensive NMR investigations, notably NOESY experiments at different temperatures. The absolute configurations of the well-known fungal metabolite diversonol (1) and of other xanthone derivatives (3, 4) were established by means of TDDFT ECD calculations. Most of the metabolites were biologically active, with antibacterial activity against Legionella pneumophila and/or antifungal activity against Microbotryum violaceum.

A chemical/computational approach to the determination of absolute configuration of flexible and transparent molecules: aliphatic diols as a case study.

By reacting flexible and optically transparent in UV-vis molecules such as 1,2-, syn- and anti-1,3-diols, 1,3-sulfanylalcohols of known absolute configuration (AC) with fluorenone dimethyl acetal, the corresponding ketals are obtained. They are conformationally well-defined (only one conformer in most cases) compounds exhibiting medium-high optical rotation (OR) values, which are independent of the solvent, and electronic circular dichroism (ECD) spectra, which show several (up to five) Cotton effects in the 350-200 nm range due to valence shell pi-->pi* transitions. These features allow simulation of the chiroptical properties of these compounds at the TDDFT/B3LYP/6-31G* level of theory to obtain, using the known ACs of these compounds, a satisfactory reproduction of the OR values (sign and order of magnitude; quantitatively, the predicted values are twice the experimental ones), and a more than satisfactory reproduction of the ECD spectra (sign, intensity, and position of the lowest-energy four Cotton effects) for all the compounds studied. Therefore, this approach can be used to assign the AC of such flexible molecules, in particular, syn-1,3-diols, which are important substrates in organic synthesis and for which nonempirical methods of AC assignment have not been devised so far. Furthermore, since the fluorene chromophore leads to the presence of several Cotton effects from, say, 350 to 200 nm, their correct simulation of sign, intensity, and position is a guarantee of the correct assignment of AC: in this way, ECD spectroscopy gains the same advantages of VCD spectroscopy, that is, the need of reproducing many ECD bands and then a solid guarantee of a correct AC assignment.

Trends in the electronic and geometric structure of non-fullerene based acceptors for organic solar cells

We constructed a database of 80 high performing non-fullerene electron acceptors and studied the common electronic and geometric properties in search of unifying design rules. We discovered that, without exception, all high performing materials are characterized by very low gap between LUMO and LUMO+1 orbitals, a feature that is consistent with microscopic models and seems to be true for all classes of compounds considered. We also confirmed that non-planarity of the acceptor is beneficial but not for all classes of acceptors. We suggested that by building similar databases and keeping it up to date it will be possible to identify statistically meaningful structure–property relations.

Lignans from Schisandra sphenathera Rehd. et Wils. and semisynthetic schisantherin A analogues: Absolute configuration, and their estrogenic and anti-proliferative activity

A new dibenzocyclooctene-type lignan, named schisandrin A1 (1), together with nine known lignans (2-10), was isolated from the stems of Schisandra sphenathera. The structure of schisandrin A1, which contains a spirocyclic epoxy unit, was established by means of spectroscopic methods. The absolute configurations of schisandrin A1 (1) and schisantherin A (2) were determined by electronic circular dichroism (CD) and TDDFT calculations, with 2 further confirmed by X-ray crystallographic data. Ten new schisantherin A derivatives (11-20) and 6,7-secoschisantherol A (2b) were synthesized. In addition, natural lignans and semisynthetic schisantherin A derivatives showed the antiproliferative activity on four human cancer cell lines and Id1 (an inhibitor of DNA binding protein) and estrogenic potency. Compounds 5, 7, and 8 exhibited very potent estrogenic activity.

Improved hemicryptophane hosts for the stereoselective recognition of glucopyranosides

Four new enantiomerically and diastereomerically pure hemicryptophane hosts (M-SSS-2/P-SSS-2 and M-RRR-2/P-RRR-2 pairs) were designed for the recognition of sugar derivatives. Their absolute configuration was determined from the circular dichroism spectra and DFT calculations. The host molecules were then used for the stereoselective recognition of glucopyranosides. Binding constants were obtained from (1)H NMR titration experiments showing an increase of affinity for this class of receptors, associated with an improved diastereo- and enantio-differentiation.

A simple dimeric model accounts for the vibronic ECD spectra of chiral polythiophenes in their aggregated states

Aggregates of chiral polythiophenes (PTs) show strong electronic circular dichroism (ECD) spectra with a unique vibronic structure. A computationally fast procedure, exploiting the quantum dynamics of the exciton-coupled electronic states of simple oligothiophene dimers as models of PT aggregates, is able to reproduce experimental vibronic ECD spectra of aggregated phases.

Simulation of Electronic Circular Dichroism of Nucleic Acids: From the Structure to the Spectrum

We present a quantum mechanical (QM) simulation of the electronic circular dichroism (ECD) of nucleic acids (NAs). The simulation combines classical molecular dynamics, to obtain the structure and its temperature-dependent fluctuations, with a QM excitonic model to determine the ECD. The excitonic model takes into account environmental effects through a polarizable embedding and uses a refined approach to calculate the electronic couplings in terms of full transition densities. Three NAs with either similar conformations but different base sequences or similar base sequences but different conformations have been investigated and the results were compared with experimental observations; a good agreement was seen in all cases. A detailed analysis of the nature of the ECD bands in terms of their excitonic composition was also carried out. Finally, a comparison between the QM and the DeVoe models clearly revealed the importance of including fluctuations of the excitonic parameters and of accurately determining the electronic couplings. This study demonstrates the feasibility of the ab initio simulation of the ECD spectra of NAs, that is, without the need of experimental structural or electronic data.

A Combined Experimental–Computational Investigation to Uncover the Puzzling (Chiro‐)optical Response of Pyridocyclophanes: One‐ and Two‐Photon Spectra

A combined experimental-computational analysis of the one- and two-photon absorption (OPA, TPA) and the electronic circular dichroism (ECD) of complex chiral shape-persistent (2,6)-pyrido[142 ]allenoacetylenic cyclophane, (P,P,P,P)-MC[142 ] enantiomers, sheds light on the origin of their peculiar spectral signatures. The study on MC[142 ], which is represented in solution by three possible conformers, indicates that two of them (chair and twist) are the prevalent conformers at room temperature; the population ratio depending on the solvent. The complex shape of the red-edge of the UV and ECD spectra is qualitatively reproduced by using vibronic calculations and assigned to progressions on the ethynyl stretchings observable only in the chair and twist conformers. The picture arising from the analysis of the linear spectra is confirmed by two-photon spectroscopies, showing that they constitute valuable tools for the exploration of high-energy electronic transitions in pyridoallenoacetylenic cyclophanes. Discrepancies among computed and experimental spectra point out that an accurate description of such complex systems with a large delocalized π framework and a dense manifold of electronic excited state remains a challenge for theoretical models.

Diastereoselective recognition of α-mannoside by hemicryptophane receptors

Four new enantiopure hemicryptophanes were synthesized and their absolute configuration was determined from experimental and calculated ECD spectra. Complexation properties of these receptors were studied toward six carbohydrate stereoisomers derived from glucose, galactose and mannose. All the receptors showed a better affinity for α-mannoside with association constants up to 2.5 × 103 M−1. One of the receptor can complex almost exclusively α-mannoside facing to α-galactoside.

Magnetic circular dichroism of porphyrin lanthanide M3+ complexes.

Lanthanide complexes exhibit interesting spectroscopic properties yielding many applications as imaging probes, natural chirality amplifiers, and therapeutic agents. However, many properties are not fully understood yet. Therefore, we applied magnetic circular dichroism (MCD) spectroscopy, which provides enhanced information about the underlying electronic structure to a series of lanthanide compounds. The metals in the M(3+) state included Y, La, Eu, Tb, Dy, Ho, Er, Tm, Yb, and Lu; the spectra were collected for selected tetraphenylporphin (TPP) and octaethylporphin (OEP) complexes in chloroform. While the MCD and UV-VIS absorption spectra were dominated by the porphyrin signal, metal binding significantly modulated them. MCD spectroscopy was found to be better suited to discriminate between various species than absorption spectroscopy alone. The main features and trends in the lanthanide series observed in MCD and absorption spectra of the complexes could be interpreted at the Density Functional Theory (DFT) level, with effective core potentials on metal nuclei. The sum over state (SOS) method was used for simulation of the MCD intensities. The combination of the spectroscopy and quantum-chemical computations is important for understanding the interactions of the metals with the organic compounds.