DFT Chemical Shift Research Articles

Vacatadithiasapphyrins: Synthesis, Structure, and Spectral and Redox Properties.

Four examples of novel aromatic [22]vacatadithiasapphyrins were synthesized by refluxing appropriate [22]telluradithiasapphyrins in 1,2-dichlorobenzene in the presence of excess HCl followed by simple column chromatographic purification. The [22]vacatadithiasapphyrins can exist in three conformers "in", "out", and "zigzag" w.r.t the butadiene moiety, and under our experimental conditions, the "out" conformer was the major compound. The X-ray structure obtained for one of the "out" conformers of vacatadithiasapphyrins revealed that the macrocycle was planar similar to its parent telluradithiasapphyrin and showed effective π-delocalization over the entire macrocyclic core. NMR studies supported the formation of the "out" conformer and suggested that the vacatadithiasapphyrins were less aromatic than the parent telluradithiasapphyrins. Density functional theory, time-dependent DFT, and nuclear independent chemical shift studies indicated that the protonated form of vacatadithiasapphyrin was more aromatic than the parent protonated telluradithiasapphyrin. The absorption spectra of vacatadithiasapphyrins showed a typical strong Soret band at ∼488 nm and four relatively broad Q-bands in the region of 590-860 nm, and electrochemical studies suggest that vacatadithiasapphyrins were easier to oxidize and easier to reduce compared to the parent telluradithiasapphyrins.

Structure reassignment of two triterpenes with CASE algorithms and DFT chemical shift predictions

Two triterpenes (14S,17S,20S,24R)-25-hydroxy-14,17-cyclo-20,24-epoxy-malabarican-3-one (CEM, 1a) and (14S,17S,20S,24R)-20,24,25-trihydroxy-14,17-cyclomalabarican-3-one (CM, 2a) with a cyclobutane ring were reported, which have the same NMR data as ocotillone (1b) and gardaubryone C (2b), respectively. An incorrect structure might be reported. Therefore, the structure reanalysis of these triterpenes was achieved by CASE algorithm and DFT chemical shift predictions, and the results showed that the structures of CEM and CM might be incorrect. To further verify the structure of compound 1, the HMBC, 1H-1H COSY and HSQC-TOCSY spectra were employed. Herein, we revised the structure of CEM and CM, and our study also showed that CASE algorithm and DFT chemical shift predictions can hold the post of effective structure reassignment method.

An Accessible Method for DFT Calculation of 11B NMR Shifts of Organoboron Compounds.

The study of boron-mediated reactions in organic synthesis and reactions of organoboron compounds is greatly facilitated by the use of 11B NMR. However, the identification and characterization of reaction intermediates in often complex systems is far from trivial, as 11B NMR does not provide any detailed structural information. Greater insight into the structures present in such systems can be obtained by using DFT chemical shift calculations to support or exclude proposed reaction intermediates. In this article, we report a rapid and accessible approach to the calculation of 11B NMR shifts that is applicable to a wide range of organoboron compounds.

A cyclo-P6 Ligand Complex for the Formation of Planar 2D Layers.

The all‐phosphorus analogue of benzene, stabilized as middle deck in triple‐decker complexes, is a promising building block for the formation of graphene‐like sheet structures. The reaction of [(CpMo)2(μ,η6:η6‐P6)] (1) with CuX (X=Br, I) leads to self‐assembly into unprecedented 2D networks of [{(CpMo)2P6}(CuBr)4]n (2) and [{(CpMo)2P6}(CuI)2]n (3). X‐ray structural analyses show a unique deformation of the previously planar cyclo‐P6 ligand. This includes bending of one P atom in an envelope conformation as well as a bisallylic distortion. Despite this, 2 and 3 form planar layers. Both polymers were furthermore analyzed by 31P{1H} magic angle spinning (MAS) NMR spectroscopy, revealing signals corresponding to six non‐equivalent phosphorus sites. A peak assignment is achieved by 2D correlation spectra as well as by DFT chemical shift computations.

NMR crystallography of ezetimibe co-crystals

An efficient, simplified protocol for solvent-drop assisted co-crystal preparation of ezetimibe (a drug for the treatment of primary hypercholesterolemia) with both imidazole and l-proline has been derived. The structures of the white powders were successfully solved via “NMR crystallography” combining solid-state NMR, powder X-ray diffraction and DFT chemical shift computations. Detailed insights into the likely crystallization mechanism were obtained from competition experiments, where efficient co-crystallization was feasible using ezetimibe monohydrate as precursor indicating that the crystal water acts as “molecular catalyst”. It was also found that co-crystallization of imidazole is favored over l-proline, thus suggesting a clear preference of neutral hydrogen bonds compared to charge-assisted motifs.

Stereochemical determination of five-membered cyclic ether acetogenins using a spin-spin coupling constant approach and DFT calculations.

Five-membered rings are of particular interest, due to their presence in some of the most common molecules in chemistry and biology. Despite their apparent simplicity, the structural resolution of these rings is complex, due to their inherent conformational flexibility. Here, we describe an application of a recently reported simple and efficient NMR protocol based on the measurement of spin-spin coupling constants to achieve the challenging relative configurations of five new halogenated C15 tetrahydrofuranyl-acetogenins, marilzafurollenes A–D (1–4) and 12-acetoxy-marilzafurenyne (5), isolated from the red alga, Laurencia marilzae. Although DFT chemical shift calculations were used to connect remote stereocenters, the NMR-based approach seems advantageous over computational techniques in this context, as the presence of halogens may interfere with reliable calculations.

Huperzimine, a novel Lycopodium alkaloid from Huperzia serrata

The structure of huperzimine, a novel Lycopodium alkaloid isolated from Huperzia serrata, was deduced from its spectroscopic properties and confirmed using GIAO DFT chemical shift calculations.

Solid-state NMR strategies for the structural characterization of paramagnetic NO adducts of Frustrated Lewis Pairs (FLPs)

By N,N addition of NO to the norbonane annulated borane-phosphane Frustrated Lewis pair (FLP) 1 a five-membered heterocyclic persistent aminoxyl radical 2 and its diamagnetic hydroxylamine reduction product 3 are prepared, and the comprehensive multinuclear solid state NMR characterization (1H, 11B, 19F, 31P) of these FLP adducts is reported. Signal quantification experiments using a standard addition method reveal that the 11B and 31P NMR signals observed in 2 actually arise from molecular impurities of 3 embedded in the paramagnetic crystal. In contrast analogous quantification experiments reveal that the 1H and 19F MAS-NMR spectra originate from spin-carrying molecules. Peak assignments are based on DFT-calculated Mulliken spin densities, which lead to the surprising result that the largest paramagnetic shift affecting a proton NMR resonance in 2 originates from intermolecular interactions. For the 19F nuclei, experiments and calculations indicate that paramagnetic shift effects are very small. In this case, assignments are based on DFT chemical shift calculations carried out on diamagnetic 3 and 19F(11B) Rotational Echo Adiabatic Passage DOuble Resonance (REAPDOR) experiments. The set of experiments described here defines an efficient strategy for the structural analysis of paramagnetic FLP adducts.

Powder crystallography of pharmaceutical materials by combined crystal structure prediction and solid-state 1H NMR spectroscopy

A protocol for the ab initio crystal structure determination of powdered solids at natural isotopic abundance by combining solid-state NMR spectroscopy, crystal structure prediction, and DFT chemical shift calculations was evaluated to determine the crystal structures of four small drug molecules: cocaine, flutamide, flufenamic acid, and theophylline. For cocaine, flutamide and flufenamic acid, we find that the assigned (1)H isotropic chemical shifts provide sufficient discrimination to determine the correct structures from a set of predicted structures using the root-mean-square deviation (rmsd) between experimentally determined and calculated chemical shifts. In most cases unassigned shifts could not be used to determine the structures. This method requires no prior knowledge of the crystal structure, and was used to determine the correct crystal structure to within an atomic rmsd of less than 0.12 Å with respect to the known reference structure. For theophylline, the NMR spectra are too simple to allow for unambiguous structure selection.

Structural characterization of metal–metal bonded polymer [Ru(L)(CO)2]n (L = 2,2′-bipyridine) in the solid state using high-resolution NMR and DFT chemical shift calculations

The metal bonded ruthenium polymer [Ru(0)(bpy)(CO)(2)](n) (bpy = 2,2'-bipyridine) is known to be a very promising and efficient solid material for catalysis applications, such as carbon dioxide electroreduction in pure aqueous media and the water-gas shift reaction. It also exhibits potential application for molecular electronics as a conductive molecular wire. The insolubility and relative air-sensitivity of [Ru(0)(bpy)(CO)(2)](n) as well as the lack of monocrystals make its structural characterization very challenging. A first approach to determine the structure of this polymer has been obtained by ab initio X-ray powder diffraction, based on the known X-ray structure of [Ru(CO)(4)](n). In order to refine this structure, a non-conventional solid-state NMR study was performed. The results of this study are presented here. The comparison of high-resolution solid-state (13)C NMR spectra of the polymer with those of the corresponding monomeric [Ru(bpy)(CO)(2)Cl(2)] or dimeric [Ru(bpy)(CO)(2)Cl](2) precursor complexes has shown a clear shift and splitting of carbonyl ligand resonances, which turns out to be linearly correlated with the redox state of the Ru (ii, i or 0, respectively). Bipyridine resonances are also affected but in a non-trivial way. Finally, in the case of the dimer, it was found that the CO peak splitting (2.7 ppm) contains structural information, e.g. the ligand staggering angle. Based on DFT chemical shift calculations on corresponding model molecules (n = 1-2), all the described experimental observations could be reproduced. Moreover, upon extending these calculations to models of increasing length (n = 3-5), it turns out that information about the staggering angle between successive ligands is actually retained in the CO NMR computed peak splitting. Turning back to experiments, the CO broad signal measured for the wire could be decomposed into a major component (at 214.9 ppm) assigned to the internal CO ligands, and a minor doublet component (216.9 and 218.1 ppm) whose splitting (2.8 ppm) contains the staggering angle information. Finally, from the relative integrals of these three components, expected to be in the ratio 1 : 1 : n-2, it was possible to tentatively estimate the length n of the polymetallic wire (n = 7).

High field 17O solid-state NMR study of alanine tripeptides

17O chemical shifts of Ala-Ala-Ala, with parallel and anti-parallel β-sheet structures, are observed using a 930-MHz high-resolution solid-state NMR spectrometer. Ala-Ala-Ala serves as a model sheet-forming peptide because it can be easily prepared as either a parallel or an anti-parallel β-sheet structure. Spectral differences between the two samples are observed which arise from molecular packing differences between the two sheet structures. DFT chemical shift calculations are performed for the two samples, and the calculated spectra are in good agreement with the experimental spectra. The DFT calculations provide insight into the nature of the chemical shift differences observed between the two sheet structures.

Studies of Complexes between Phenyllithium and (−)-Sparteine in Ether Solutions

NMR studies and DFT chemical shift calculations of (−)-sparteine−phenyllithium (PhLi) complexes are reported. It is found that PhLi forms a tetrameric ladder complex in diethyl ether (Et2O) solution complexed by (−)-sparteine. The tetrameric ladder core is terminated by (−)-sparteine ligands. Tetrahydrofuran (THF) coordinates more strongly to PhLi than (−)-sparteine; thus in THF solvent only the THF-solvated PhLi dimers are observed, while (−)-sparteine is free in solution. However, addition of substoichiometric quantities of THF to the Et2O solution of the (−)-sparteine-solvated PhLi ladder tetramer results in PhLi dimers solvated by one (−)-sparteine and one THF molecule. GIAO DFT calculations on model systems at the B3LYP(6-311+G(d,p))//B3LYP(6-31+G(d) level of theory provide details regarding the solvation at lithium in these complexes, which supports the NMR results.

Structure of pyrimidinocyclophanes in solution by NMR

Abstract The conformations and self-associative properties of novel pyrimidinocyclophanes with a substituted nitrogen atom in a spacer have been studied using several independent NMR methods (NOE, aromatic shielding effect, 2D DOSY, GIAO DFT chemical shift calculations, DNMR) in a variety of solvents, in acidic and basic media. At room temperature the title compounds in neutral solution are in slow exchange on the NMR time-scale and exist in a folded conformation. In the acidic medium protonation occurs at the bridge nitrogen, and that leads to dramatic modifications of the structure and dynamics of the compound. The protonated form exists at the equilibrium of ‘folded’ and ‘extended’ conformers. Moreover, the protonated form is prone to association and can be effectively described as a dimer at room temperature.