Alessandro Bagno

Addressing the Stereochemistry of Complex Organic Molecules by Density Functional Theory-NMR: Vannusal B in Retrospective

We have employed density functional theory (DFT) protocols to calculate the NMR properties of the vannusals, a class of natural products whose structures have been the subject of recent investigations. The originally assigned structure of vannusal B was revised after a long synthetic journey which generated a series of closely related diastereomers. In this work we show how DFT calculations based on density functionals and basis sets designed for the prediction of NMR spectra (M06/pcS-2 level of theory) can be used to reproduce the observed parameters, thereby offering to the synthetic chemist a useful tool to discard or accept putative structures of unknown organic molecules.

Complete prediction of the 1H NMR spectrum of organic molecules by DFT calculations of chemical shifts and spin-spin coupling constants.

1H NMR chemical shifts and coupling constants for several aromatic and aliphatic organic molecules have been calculated with DFT methods. In some test cases (furan, o-dichlorobenzene and n-butyl chloride) the performance of several functionals and basis sets has been analyzed, and the various contributions to spin-spin coupling (Fermi-contact, diamagnetic and paramagnetic spin-orbit) have been evaluated. The latter two components cancel each other, so that the calculation of the contact term only is sufficient for an accurate evaluation of proton-proton couplings. Such calculated values are used to simulate the 1H NMR spectra of organic molecules with complicated spin systems (e.g. naphthalene, o-bromochlorobenzene), obtaining a generally very good agreement with experimental spectra with no prior knowledge of the involved parameters.

Predicting the NMR Spectra of Paramagnetic Molecules by DFT: Application to Organic Free Radicals and Transition-Metal Complexes

Nuclear shieldings, including the Fermi contact and pseudocontact terms, have been calculated with DFT methods in a variety of open-shell molecules (nitroxides, aryloxyl and various transition-metal complexes), thereby predicting (1)H and (13)C chemical shifts. In general, when experimental data are reliable a good agreement with experimental values is observed, thus demonstrating the predictive power of DFT also in this context. However, the general accuracy is lower than that for closed-shell species. A few inconsistencies in literature values are reconciled by reassigning some shifts. Structural, magnetic, and dynamic parameters have also been put into the Solomon-Bloembergen equations to predict signal line shapes, in particular those of signals that are difficult to locate or are undetectable. Guidelines are provided to predict the order of magnitude of relaxation rates. It is shown that DFT-predicted paramagnetic shifts can greatly assist in obtaining and understanding the NMR spectra of paramagnetic molecules, which generally require different experimental strategies and exhibit problems in detection and assignment.

NMR Spectra of Terminal Oxo Gold and Platinum Complexes: Relativistic DFT Predictions

Transition metals that have a high d-electron count do not easily form terminal oxo complexes, as the metal valence electrons tend to repel those of the oxo ligand. Indeed, until recently, very few such complexes (of Ir, Fe, and Re) were known. Complexes with late-transition and post-transition elements such as Pd, Pt, and Au are proposed to be reactive intermediates in oxidation reactions catalyzed by noble metals. After some inconclusive studies were reported by other research groups, Lee et al. reported the crystal structure of the polyoxometalate (POM) a[SiPt2W10O40] 8 , for which terminal oxo Pt=O bonds were claimed, although positional disorder did not allow for an accurate location of the Pt atoms. Hill and co-workers have reported Pt, Pd, and Au [6] oxo POMs. The bonding arrangements of Pt, Pd, and Au in the solid state were similar, and feature a linear [O=M OH2] n+ moiety embedded in the polyoxotungstate framework with a relatively short (1.6–1.8 ) M=O bond and a longer (2.0–2.3 ) M OH2 bond. Lee, Kortz, and coworkers provided crystal structures for [PtM6O24] 8 (M = Mo, W) and [H2PtV9O28] 5 , where no Pt-oxo bond was claimed. Shortly thereafter, the two research groups challenged each other s contentions on the characterization of the respective structures by NMR spectroscopy. Thus, whereas the V and Pt NMR spectra of [H2PtV9O28] 5 were consistent with the crystal structure, in the case of oxo Pd, Pt, and Au POMs, the W and Pt NMR spectra failed to yield any information. For the Pd and Au complexes, P and O NMR spectra were obtained. However, the P NMR signals span a narrow range of frequencies and their use for structure elucidation is questionable. Milstein and co-workers reported a pincer-type Pt-oxo complex, 11] the Pt NMR spectrum of which was consistent with the proposed structure. However, the lack of any reference data calls for some caution; furthermore, a crystal structure be could not be obtained. Both studies 10] indicate a diverse reactivity with facile oxygen transfer to other substrates. However, terminal oxo POMs cannot be characterized in solution by using established NMR techniques. Heteronuclear magnetic resonance is often fraught with technical difficulties: 1) without prior knowledge, it may be difficult to locate the signals of interest; 2) for Pt and W NMR spectroscopy, chemical shift anisotropy (CSA) may lead to broad lines, but is welldocumented only for Pt. Thus, there seem to be unexplained features that render NMR spectroscopic characterization elusive. Numerous studies have demonstrated the capability to predict the NMR properties of heavy-atom nuclei by means of relativistic density functional theory. Herein, we present computational results that concern the electronic structure of terminal oxo Pt and Au complexes and their O, Pt, and W NMR spectra. We have investigated Kortz s Pt decavanadate [H2PtV9O28] 5 (PtV9); Milstein s pincer complex [Pt(O) PCN] (PtO PCN), where PCN is the tridentate ligand C6H3[CH2P(tBu)2](CH2)2N(CH3)2; [10] Hill s terminal oxo POM [P2W20O70Au(O)(OH2)3] 9 (P2W20Au), its lacunary ligand [P2W20O70(OH2)2] 10 (P2W20), and the isostructural [P2W21O71(OH2)3] 6 (P2W21) (Figure 1 and Scheme 1). We firstly computed the HOMO–LUMO gaps (DE ; HOMO = highest occupied molecular orbital, LUMO = lowest unoccupied molecular orbital) at the spin-orbit (ZSO) level, since for P2W20Au, self-consistent field (SCF) convergence could not be achieved in calculations at the scalar level (ZSC), owing to the extremely small DE value (see below). On the other hand, inclusion of spin-orbit coupling is associated with a lower orbital symmetry, which allows for a greater flexibility in the SCF. PtV9, P2W21, and P2W20 have DE = 1.5–2.0 eV; most POMs have DE = 2–3 eV. 25] For PtO–PCN, DE is substantially smaller (0.40 eV); however, the complex is prepared in the presence of donor molecules (water, acetone), which may bind to Pt (DE = 5.0 and 5.5 kcal mol , respectively, without vibrational corrections). In such adducts, DE rises to 1.1–1.2 eV. For P2W20Au, DE is only 0.03 eV. In PtV9, the HOMO is localized over the PtO6 unit, and the LUMO delocalized over the entire framework, with hardly any contribution from Pt. PtO PCN features both frontier molecular orbitals (FMOs) localized on the Pt=O bond. However, in solvent-coordinated species, the LUMO becomes strongly delocalized onto the solvent. In P2W20Au both FMOs are largely localized on the Au=O fragment and W(3i) (Figure 2 and S1 in the Supporting Information). The extremely small DE value implies very low-lying excited states and a facile switch between nucleophilic and [*] Prof. A. Bagno, Dr. R. Bini Department of Chemistry, University of Padova via Marzolo, 1-35131 Padova (Italy) Fax: (+ 39)049-827-5239 E-mail: alessandro.bagno@unipd.it Homepage: http://www.chimica.unipd.it/alessandro.bagno

Can two molecules have the same NMR spectrum? Hexacyclinol revisited.

An in-depth DFT computational investigation (B97-2/cc-pVTZ level) of the 1H and 13C NMR spectra of the recently disputed natural substance hexacyclinol, including J(1H,1H) couplings, is presented. Structures 1 and 2 have been compared with regard to the suggested possibility that two molecules have very similar NMR spectra as to be indistinguishable. Despite a remarkable similarity of functional groups present, the two calculated spectra differ in many features related both to chemical shifts and connectivities.

Through‐Space Spin–Spin Coupling in van der Waals Dimers and CH/π Interacting Systems. An Ab Initio and DFT Study

The through-space J(HH) and J(CH) spin-spin coupling constants of model van der Waals dimers (involving methane, ethylene, and benzene), and of selected compounds showing the CH/pi interaction, have been investigated by means of DFT and ab initio calculations. In the range of intermolecular separations for which the interaction is stabilizing, weak couplings (0.1-0.3 Hz) are predicted for J(CH), while the corresponding J(HH) couplings are much smaller. The relative contributions (Fermi-contact, spin-orbit, and spin-dipole) are strongly dependent on the geometry of the dimers and on the distance; the non-negligible values of J(CH) for pi systems stem largely from an incomplete cancellation of spin-orbit terms. The results obtained for the larger molecules, that is, acetonitrile@calix[4]arene 5, the imine 6, and the aryl ester 7 are consistent with those on the model dimers. For 7, the occurrence of a through-space mechanism for the transmission of coupling is established by examining trends in the magnitude of couplings as a function of the number of intervening covalent bonds.

[60]Fullerene as a substituent.

The substituent effect of the dihydro[60]fullerenyl group and its hydrophobic parameters have been evaluated quantitatively. The substituent constant has been determined from the pK value of a fullerene-based, para-substituted benzoic acid 1 in 80% dioxane/water (v/v) by NMR spectroscopy. The resulting Hammett sigma value of 0.06, consistent with a small electron-withdrawing effect of C(60), is a consequence of the fact that only inductive effects can be transmitted through the two tetracoordinate carbon atoms between the fullerene pi system and the para-position of the benzoic acid moiety in 1. The parameter pi, which describes the hydrophobic character of the substituent C(60), has been evaluated as the difference between that of 1 and model compound 2. The pi value, which is larger than 3, indicates that the fullerene cage imparts high hydrophobicity to the molecule to which it is attached. Finally, we have evaluated how the fullerene spheroid influences the acid-base properties and nucleophilicity of the pyrrolidine nitrogen in a suitably functionalized fulleropyrrolidine. The fulleropyrrolidine 4 (pK(BD)(+)=5.6) is six orders of magnitude less basic and 1000 times less reactive than its model 3 (pK(BD)(+)=11.6). This may be related to through-space interactions of the nitrogen lone pair and the fullerene pi system.

Site of Protonation of Carboxylic and Non‐Carboxylic Amides in the Gas Phase and in Water

Wheredoestheprotongo? Amides possess at least two protonation sites—the nitrogen and the acid residue (figure). The interplay of quantum chemical calculations and heteronuclear NMR measurements allows us to pinpoint the preferred one.

Predicting the 1H and 13C NMR spectra of paramagnetic Ru(III) complexes by DFT

Nuclear shieldings, including the Fermi‐contact and pseudocontact terms, have been calculated with density functional theory (DFT) (nonrelativistic and relativistic) methods in several Ru(III) complexes, thereby predicting 1H and 13C paramagnetic shifts. A fair agreement with experimental values is observed. Structural, magnetic and dynamic parameters have also been input to the Solomon–Bloembergen equation in order to predict signal lineshapes. It is shown that DFT‐predicted paramagnetic shifts can greatly aid in obtaining and understanding NMR spectra of paramagnetic Ru(III) complexes. Copyright

Effective core potential DFT calculations of nuclear shielding as a tool for the prediction and assignment of the tungsten chemical shift in mono- and polynuclear complexes

Abstract The shielding of the 183 W nucleus in mononuclear tungsten complexes and in the Keggin heteropolyoxotungstate PW 12 O 40 3− has been investigated by a density functional theory (DFT) method with effective core potentials. Calculated shieldings correlate with experimental data, although they are one order of magnitude lower than the experimental values, which is reflected in low slopes (