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Carlo Rosini

Publications and source records attributed to Carlo Rosini.

17 recordsLinked to original sources
PubMed2006

Flexible biphenyl chromophore as a circular dichroism probe for assignment of the absolute configuration of carboxylic acids.

A general and nonempirical approach to determine the absolute configuration (AC) of 2-substituted chiral carboxylic acids by circular dichroism (CD) spectroscopy has been developed. In this protocol, the chiral acids are converted to the corresponding biphenyl amides, in which a flexible biphenyl probe gives rise to a Cotton effect at 250 nm (A band) in the CD spectrum, the sign of which is related to the acid AC. Two different mechanisms of transfer of chirality from the acid stereogenic center to the biphenyl moiety are operative in amides derived from 2-alkyl- and 2-aryl-substituted acids, respectively. For both classes of compounds, a model has been defined which allows one to predict, for a given acid AC, the preferred twist of the biphenyl moiety and thus the sign of the A band in the CD spectrum, related to the biphenyl torsion. Interestingly, while in alkyl-substituted substrates the preferred biphenyl twist is determined only by steric interactions, in the aryl-substituted ones the structure of the prevalent conformer and thus the biphenyl twist are dictated by arene-arene edge-to-face stabilizing interactions. Following this protocol, the AC of a 2-substituted chiral acid can be established simply by preparing its biphenyl amides, recording the CD spectrum, and looking at the sign of the A band. From the sign of such a band, the torsion of the biphenyl can be deduced and then the acid AC. Substrates having different structures and functionalities have been investigated, always obtaining reliable AC assignments by this simple protocol.

Journal Article↗
PubMed2006

Fenchone, camphor, 2-methylenefenchone and 2-methylenecamphor: a vibrational circular dichroism study.

We report and discuss the infrared (IR) vibrational circular dichroism (VCD) spectra of the enantiomeric pairs of the olefin derivatives of fenchone (1,3,3-trimethyl-2-methylenebicyclo[2.2.1]heptane) and camphor (1,7,7-trimethyl-2-methylenebicyclo[2.2.1]heptane), respectively, together with those of the parent molecules. The VCD spectra were taken in three spectral regions: the mid-IR region, encompassing the fundamental deformation modes, the region of CH-stretching fundamental modes and the NIR-region between 1100 and 1300 nm, which corresponds to the second CH-stretching overtone. The VCD and absorption spectra in the first two regions are analyzed by use of current density functional theory (DFT) calculations. The NIR region is analyzed by a protocol that consists of the use of DFT-based calculations and in assuming local mode behavior: the local mode approach is found appropriate for interpreting the absorption spectra and, for the moment, acceptable for calculating NIR-VCD spectra. The analysis of the first region allows us to track the contribution of the C=O group in the vibrational optical activity of C-C stretching modes; notable differences are indeed found in olefins and ketones. On the contrary, in the other two regions the VCD spectra of olefins and ketones are more similar: in the normal mode region of CH stretching fundamentals the spectra are determined by the mutual orientation of the CH bonds; in the second overtone local mode region olefins and ketones signals show some differences.

Camphanes↗
PubMed2005

Enantioselective nonsteroidal aromatase inhibitors identified through a multidisciplinary medicinal chemistry approach.

To identify enantioselective nonsteroidal aromatase inhibitors, a multidisciplinary medicinal chemistry approach was pursued. First, our earlier CoMFA model [Bioorg. Med. Chem. 1998,6, 377-388] was extended taking purposely into account previously discovered enantioselective aromatase inhibitors. The 3D QSAR model was then exploited to design chiral ligands, whose configurational assignment was obtained, after HPLC separation, by means of a combination of circular dichroism measurements and time dependent density functional calculations. Finally, the new enantiomeric inhibitors were separately tested to ascertain both their potency against the cytochrome P450 aromatase (CYP19; EC 1.14.14.1), and their selectivity relative to another enzyme of the P450 family. A satisfactory agreement between experimental and predicted data allowed us to assert that a properly built "enantioselective CoMFA model" might constitute a useful tool for addressing enantioselective ligands design.

Aromatase↗
PubMed2005

Theoretical simulation of the electronic circular dichroism spectrum of calicheamicin.

The aglycon, or so-called 'warhead' portion, of several potent 10-membered ring enediyne antitumor antibiotics contain dienonecarbamate and enediyne chromophores in an unusual bicyclic ring structure in which these two subunits are essentially orthogonal to each other. The circular dichroism (CD) spectra of the calicheamicin, esperamicin, and shisijimicin A families, all of which contain this bicyclic ring system, exhibit a characteristic negative exciton coupled CD at about 310 and 270 nm. This signature CD feature suggested the absolute stereochemical relationship between these chromophores as originally assigned and which was later confirmed by stereospecific total synthesis. Because of the unique nature of this chromophoric interaction and the importance of using this CD spectral feature in the assignment of the absolute stereochemistry of other related enediynes, we report here simulations of the CD spectra of the calicheamicin aglycon A, and of two other truncated models, B and C, by using density functional theory (DFT) and the DeVoe coupled oscillator approach. The DFT calculations provide a strong theoretical basis that the planar enediyne chromophore alone gives a negligible CD contribution, while that coming from the twisted dienonecarbamate is much more substantial. However, the shape and the largest part of the intensity of experimental CD spectrum can only be reproduced when the two unsaturated moieties are simultaneously present. Thus, the exciton coupling between the two chromophores provides the most important contribution to the experimental CD spectrum of calicheamicin. This conclusion is in full agreement with the results from the DeVoe calculation.

Aminoglycosides↗
PubMed2005

Determination of the absolute configuration of flexible molecules by ab initio ORD calculations: a case study with cytoxazones and isocytoxazones.

Ab initio calculations of the optical rotatory power of the natural cytokine modulator cytoxazone 1 and its trans-diastereomer 2, as well as the structural isomers cis-3 and trans-4 isocytoxazones, have been performed at four different wavelengths (589, 546, 435, and 405 nm) by Density Functional Theory. The calculation of ORD curves provides a reliable method for the assignment of absolute configuration of these conformationally flexible molecules. The absolute configurations of isocytoxazones has been established as (+)-(4R,5S)-cis-3 and (+)-(4S,5S)-trans-4.

Magnetic Resonance Spectroscopy↗
PubMed2005

Assignment of the absolute configuration of (+)-diplopyrone, the main phytotoxin produced by Diplodia mutila, the pathogen of the cork oak decline, by a nonempirical analysis of its chiroptical properties.

The nonempirical assignment of the absolute configuration of (+)-diplopyrone, the main phytotoxin of Diplodia mutila, i.e., an endophytic fungus, widespread in Sardinian oak forests, and considered one of the main causes of cork oak decline, has been approached by two different methods: (a) the exciton analysis of the circular dichroism (CD) spectrum and (b) the ab initio calculation of the optical rotatory power. Both methods indicate that (+)-diplopyrone is 6-[(1S)-1-hydroxyethyl]-2,4a(S),6(R),8a(S)-tetrahydropyrano[3,2-b]pyran-2-one, so the stereostructure of this important biomolecule is safely determined for the first time. A comparison of advantages and limitations of the two methods of analysis is also presented.

Circular Dichroism↗
PubMed2004

Non-empirical assignment of the absolute configuration of (-)-naringenin, by coupling the exciton analysis of the circular dichroism spectrum and the ab initio calculation of the optical rotatory power.

The non-empirical assignment of the absolute configuration of (-)-naringenin, the aglycone of (-)-naringin, a flavanone glycoside abundant in the albedo of immature grapefruits and showing several interesting biological properties, has been approached by two different methods: (a) the exciton analysis of the circular dichroism (CD) spectrum and (b) the ab initio calculation of the optical rotatory power. Both the methods indicate the configurational correlation (-)/(S), as empirically suggested by Gaffield. A comparison of advantages and limitations of the two methods of analysis is also presented.

Circular Dichroism↗
PubMed2004

Ab initio calculation of optical rotatory dispersion (ORD) curves: a simple and reliable approach to the assignment of the molecular absolute configuration.

In this paper, both Hartree-Fock (HF) and density functional theory (DFT) methods have been used to make ab initio calculations of the optical rotatory power of selected molecules at several wavelengths; that is, part of the optical rotatory dispersion (ORD) curve has been predicted. This approach constitutes a new, simple, and reliable method to assign the molecular absolute configuration, at least for rigid molecules such as those studied in the present work. In fact, in this way, it is possible to overcome the difficulties connected to some relevant cases, in particular that of (-)-beta-pinene, for which even a very high-level (DFT/B3LYP/6-311++G(2d,2p)) calculation affords the wrong sign of the optical rotation at 633 nm. On the contrary, the predicted ORD curve, even using small basis sets, reproduces (below 400 nm) the experimental trend well, allowing for the correct configurational assignment. This result clearly shows that to have a reliable configurational assignment the comparison between experimental and predicted rotation values must be carried out at different wavelengths and not at a single frequency. The reason for this is that working at wavelengths approaching the absorption maximum the [alpha](lambda) values become larger and their prediction becomes more reliable. Coupling the use of an inexpensive instrument (a polarimeter working at a few wavelengths) with the use of a DFT-calculation package can also allow the experimental organic chemist to arrive, quickly and reliably, at the assignment of the molecular absolute configuration.

Journal Article↗
PubMed2004

A general and nonempirical approach to the determination of the absolute configuration of 1-aryl-1,2-diols.

We describe herein a simple, general, and reliable nonempirical approach, based on the exciton coupling method, to assign the absolute configuration of the benzylic stereogenic center of 1-aryl-1,2-diols. According to this method, it is only necessary to prepare the 4-biphenylboronic esters of the diols and to record their CD spectra in the 230-300 nm range, i.e., in the range corresponding to the long-axis (1)L(a) transition of the biphenyl chromophore. From the sign of the CD couplet or Cotton effect at 260 nm it is possible to know the chirality defined by the aryl and biphenyl chromophore transitions and then to determine the absolute configuration of the benzylic carbon. By this approach, simple rules have been formulated which allow us to establish the absolute configuration of many classes of 1-aryl-1,2-diols.

Journal Article↗
PubMed2004

A chiroptical molecular switch with distinct chiral and photochromic entities and its application in optical switching of a cholesteric liquid crystal.

Two new structurally related photoswitches are described, in which azobenzene photochromism is combined with the chirality of a 2,2'-dihydroxy-1,1'-binaphthyl unit. In system 1 the chiral binaphthyl moiety is bridged by a methylene tether, locking the biaryl chirality while in system 2 the biaryl core is unbridged and has considerable conformational flexibility. Both compound are capable of inducing cholesteric liquid crystalline phases and proved to be good photoswitches both in solution and in a liquid crystalline matrix. Compound 2 is capable of completely reversing the liquid crystalline chirality which is unique for a chiroptical molecular switch where the switching unit and the chiral moiety are separate entities.

Journal Article↗
PubMed2004

Structural determinations by circular dichroism spectra analysis using coupled oscillator methods: an update of the applications of the DeVoe polarizability model.

The exciton (coupled oscillator) model for optical activity is a very useful and powerful method which allows to analyze a circular dichroism (CD) spectrum in a nonempirical way, arriving at a safe assignment of the absolute configuration of organic and inorganic compounds. Usually in this model only the exciton coupling of two electrically allowed transitions (oscillators) is taken into account. This approach has the important advantage of an easy application but, sometimes, it may lead to wrong results. Thus, in this review article a more general treatment, which allows considering the simultaneous coupling of several oscillators, i.e., the DeVoe model, is presented and critically analyzed, discussing in detail the latest applications reported in the literature. In the authors opinion, since the DeVoe model joins generality and reliability requiring an almost negligible computational effort, it represents the method of choice for stereochemical assignments, even by nonspecialists.

Journal Article↗
PubMed2003

Circular dichroism spectra and absolute configuration of some aryl methyl sulfoxides.

The absorption and circular dichroism (CD) spectra of three aryl sulfoxides, i.e. (-)-(S)-1-naphthyl methyl sulfoxide, (S)-1, (-)-(S)-1-(2-methyl)naphthyl methyl sulfoxide, (S)-2 and (-)-(S)-9-phenanthryl methyl sulfoxide, (S)-3, have been interpreted by means of the coupled oscillator model formulated by DeVoe. Theoretical spectra have been calculated starting from input geometries provided by molecular mechanics (MMX) calculations and by employing standard spectroscopic parameters to describe the allowed transitions of the aromatic and the sulfoxide chromophores. The satisfactory agreement between the predicted and experimental spectra allows us to confirm the configurational assignment of these compounds as (-)/(S). The analysis of CD spectra, affording the right assignment of the absolute configuration (AC) of the alkyl aryl sulfoxides, then offers a practical alternative to the more complex vibrational circular dichroism spectroscopy and ab initio optical rotation calculation techniques that have been used very recently to assign the AC of (-)-2 and (-)-3.

Journal Article↗
PubMed2003

Assignment of the molecular absolute configuration through the ab initio Hartree-Fock calculation of the optical rotation: can the circular dichroism data help in reducing basis set requirements?

In this paper the calculation of the optical rotation (OR) of some rigid organic molecules, using the Hartree-Fock method with small (6-31G, DZP) basis sets, has been studied thoroughly to carefully evaluate the scope and limitations of this method, previously introduced by other authors. Calculations on test molecules (compounds 1-13) together with a careful analysis of their CD spectra allow a simple criterion for the reliability of this approach to be formulated: for unsaturated and/or aromatic (i.e., absorbing in the near-UV region) molecules, if the [alpha](D) is quantitatively determined by the lowest energy Cotton effect (at wavelengths >220 nm), then the HF/6-31G result is reliable. The usefulness of this method for the experimental organic chemist has been further demonstrated because the OR (sign and order of magnitude) of compounds 14-19 (i.e., large molecules having considerable interest in organic chemistry), which fulfill the above criterion and for which an extended basis set treatment is not feasible owing to their size, is correctly predicted.

Journal Article↗
PubMed2003

Conformational studies by dynamic NMR. 93.(1) Stereomutation, enantioseparation, and absolute configuration of the atropisomers of diarylbicyclononanes.

The structure of 9-(4-methoxyphenyl)-9-(3-methylphenyl) bicyclo[3.3.1]nonane (1) has been determined by single-crystal X-ray diffraction, and the rotation barriers about the two aryl-C9 bonds have been measured by variable temperature NMR spectroscopy in solution. In the case of 9-(4-methoxyphenyl)-9-(1-naphthyl)bicyclo[3.3.1]nonane (3), the barrier involving the naphthyl-C9 rotation was found to be so high as to allow the physical separation of the two atropisomers by enantioselective HPLC at ambient temperature: the absolute configuration could be established on the basis of the corresponding CD spectra. It was also observed that the Ar-C9 rotation barriers of monoaryl-substituted nonanes are much lower than those of the corresponding diaryl-substituted nonanes.

Journal Article↗
PubMed2003

A correlation between the absolute configuration of alkyl aryl sulfoxides and their helical twisting powers in nematic liquid crystals.

In this paper, for the first time, a systematic experimental and theoretical analysis of the cholesteric induction due to solutes whose chirality is originated only by a single stereogenic center has been carried out. The twisting power beta of a series of alkyl aryl sulfoxides has been determined in several nematic solvents. The sign of beta, which reflects the handedness of the induced helical arrangement of the solvent molecules, correlates with the configuration of the stereogenic sulfur in the nematic solvents E7, Phase 1083, and ZLI 2359: (S)-configurated dopants induce (M)-chiral nematics. (S)-Configurated cyclic sulfoxides, which are forced to adopt a different conformation with respect to the parent acyclic compounds, induce, instead, right-handed chiral nematics. The experimental data have been interpreted in the light of the surface chirality model, which allows the calculation of beta in terms of the molecular properties of the dopant, namely, the anisotropy and helicity of its molecular surface. The calculations reliably reproduce the behavior experimentally observed. The more flexible, open-chain compounds investigated induce chiral nematics of opposite handedness in MBBA and Phase 1053: temperature-dependent experiments point out the importance of the conformation in determining the effective sign of beta. The results have been discussed in terms of different conformation populations in these latter solvents with respect to E7, Phase 1083, and ZLI 2359.

Journal Article↗
PubMed1999

Induction of Cholesteric Mesophases by Simple Cyclic Derivatives of p,p'-Disubstituted 1,2-Diphenylethane-1,2-diols: Importance of Shape and Polarizability Effects.

A systematic study of the cholesteric induction in nematic solvents (MBBA and E7) by some cyclic derivatives of unsubstituted and p,p'-disubstituted-1,2-diphenylethane-1,2-diols shows that the values of the twisting power are significantly dependent on the nature of the link connecting the two oxygen atoms and on the nature of the p,p'-substituents. This result has been interpreted considering that the nature of the bridge affects the overall molecular shape and the p,p'-substituents affect both the molecular polarizability and shape. This investigation points out that the polarizability of the solute and the solvent is the main parameter in determining the value of the twisting power while electrostatic arene-arene interactions contribute to a less extent. It has been also observed that solutes having the same structure and the same absolute configuration can induce cholesteric helix of opposite sign depending on the substituent on the aromatic ring. This finding indicates that configurational assignments by cholesteric induction are reliable only if high values of twisting power are measured.

Journal Article↗