Radek Marek

15N NMR Spectroscopy in Structural Analysis

The implementation of both the directly and the inversely detected 15N NMR techniques at the natural abundance level of the 15N isotope is demonstrated for a diverse array of structural problems in organic chemistry. Following the application of 15N NMR to the elucidation of the structures of natural compounds and synthetic products, the 15N-detected electron distribution in such molecules and following their reactions with other molecules and ions is discussed. A significant part of the 15N structural analysis is devoted to the description of tautomers, rotamers, conformers, configurational isomers, and regioisomers. The changes in the 15N parameters induced in structurally related compounds are described briefly. At present, the optimum probe-tube-sample configuration makes it possible to acquire inverse-detected 1H-15N correlation spectra on samples, where the total available sample is limited to amounts of < 1 mg (for molecules [sim] 400 MHz). 15N NMR spectroscopy at the natural abundance level of 15N nuclei has become a powerful tool which has substantially extended the analytical arsenal of organic chemists.

15N NMR Spectroscopy in Structural Analysis: An Update(2001-2005)

Since our previous review article (Curr. Org. Chem. 2002, 6, 35), significant improvements and an array of 15N NMR applications in structural analysis have been published. This report aims to update coverage of improvements in methodology and various types of applications published over the period 2001 - 2005. Substantial progress in cryogenic probe technology and the commercial availability of cryoprobes have facilitated the measurement of 15N NMR parameters. The number of solid-state applications has increased significantly during the past few years. In contrast to our previous review, this article covers 15N solid-state studies. The 15N NMR chemical shifts of organic molecules are routinely measured by using cross-polarization magic-angle spinning (CP/MAS) techniques. The principal values of the chemical shift tensors can also be determined. 1H-15N and 2H-15N distance measurements made by means of 1H detection are currently used in NMR crystallography. User friendly quantum chemical programs allow for the routine calculation of 15N chemical shielding and indirect spin-spin coupling constants, especially using density functional theory (DFT). Applications of 15N NMR spectroscopy in various fields of chemistry are summarized here. Major sections represent tautomerism, complexation, protonation, and hydrogen bonding. The other topics comprise N-alkylation, N-oxidation, regioisomerism, and changes in configuration or conformation.

Gradient-enhanced HSQC experiments for phase-sensitive detection of multiple bond interactions

Observation of remote connectivities and determination of long range coupling constants by 1H-X (13C, 15N and 77Se) gradient-enhanced phase-sensitive HSQC is reported.

All-Metal Aromaticity: Revisiting the Ring Current Model among Transition Metal Clusters

We present new insight into the nature of aromaticity in metal clusters. We give computational arguments in favor of using the ring-current model over local indices, such as nucleus independent chemical shifts, for the determination of the magnetic aromaticity. Two approaches for estimating magnetically induced ring currents are employed for this purpose, one based on the quantum theory of atoms in molecules (QTAIM) and the other where magnetically induced current densities (MICD) are explicitly calculated. We show that the two-zone aromaticity/antiaromaticity of a number of 3d metallic clusters (Sc3(-), Cu3(+), and Cu4(2-)) can be explained using the QTAIM-based magnetizabilities. The reliability of the calculated atomic and bond magnetizabilities of the metallic clusters are verified by comparison with MICD computed at the multiconfiguration self-consistent field (MCSCF) and density functional levels of theory. Integrated MCSCF current strength susceptibilities as well as a visual analysis of the calculated current densities confirm the interpretations based on the QTAIM magnetizabilities. In view of the new findings, we suggest a simple explanation based on classical electromagnetic theory to explain the anomalous magnetic shielding in different transition metal clusters. Our results suggest that the nature of magnetic aromaticity/antiaromaticity in transition-metal clusters should be assessed more carefully based on global indices.

Cytotoxic Activities of Several Geranyl-Substituted Flavanones

Nine geranylated flavanones isolated from the fruits of Paulownia tomentosa (4-12) and two from the roots of Morus alba (13 and 14) were examined for cytotoxicity to selected human cancer cell lines and normal human fibroblasts. Cytotoxicity was determined in vitro using a calcein AM cytotoxicity assay. Cytotoxicity for the THP-1 monocytic leukemia cell line was tested using erythrosin B cell staining. The geranylated compounds tested were compared with the known simple flavanone standards taxifolin (1), naringenin (2), and hesperetin (3) and with the standard anticancer drugs olomoucine II, diaziquone, and oxaliplatin and the antineoplastic compound camptothecin, and showed different levels of cytotoxicity. The effects of structural changes on cytotoxic activity, including geranyl substitution of the flavanone skeleton and the oxidation pattern of ring B of the flavanones, are discussed.

NMR Studies of Purines

This contribution reviews applications of NMR spectroscopy in the investigation of the structure and the intra- and intermolecular interactions of purine derivatives. Purines represent a highly important class of heterocyclic compounds that are widely distributed in all living organisms, not only as constituents of nucleic acids, but also as signal molecules. Their structure, electron distribution, and proton-transfer processes determine their chemical reactivity, interactions with solvents, and, subsequently, also their biological activity and function. Along with X-ray diffraction, NMR spectroscopy represents one of the most important experimental tools for investigating molecular topology at the atomic level. In the following text, NMR methods suitable for studying the purine structure and their application to exploring samples at natural levels of the 13C and 15N isotopes are briefly reviewed. As will be shown, isotropic 13C and 15N chemical shifts, 1H-13C one- and three-bond J-coupling constants and 1H-15N one- and two-bond couplings are the commonly used characteristic parameters for NMR in the solution state. In the solid state, CP MAS spectra of powder samples provide the principal values of the chemical-shift tensors. Quantum chemical calculations on the DFT level support and explain the experimental data. Due to the extremely wide scope of the topic, no attempt is made to cover the area completely. Rather, typical examples of applications and recently published contributions in all of the areas identified above are included to provide the reader with a summary of the current efforts to increase our knowledge and understanding of the interactions at the atomic, molecular and intermolecular level in purine and its derivatives.

13C Chemical Shift Tensors in Hypoxanthine and 6-Mercaptopurine: Effects of Substitution, Tautomerism, and Intermolecular Interactions

Principal values of the (13)C chemical shift tensor (CST) are measured for two biologically interesting and structurally related compounds, hypoxanthine and 6-mercaptopurine, and differences in the values are discussed with an attempt to reveal chemical shifts sensitive to substitution and prototropic tautomerism in the purine ring. Furthermore, methods of density-functional theory (DFT) are used to calculate principal values of the (13)C chemical shift tensor and orientations of the principal components. Values calculated for isolated molecules are compared to those for several supramolecular clusters and then to experimental data to investigate the degree of modulation of the (13)C CSTs by molecular packing. Focusing on the protonated carbons, C2 and C8, which are crucial for relaxation measurements, we show that neglecting intermolecular interactions can lead to errors as large as 30 ppm in the delta(22) principal component. This has significant implications for the studies of molecular dynamics, employing spin relaxation, in large fragments of nucleic acids at high magnetic fields.

Understanding the electronic factors responsible for ligand spin-orbit NMR shielding in transition-metal complexes

The significant role of relativistic effects in altering the NMR chemical shifts of light nuclei in heavy-element compounds has been recognized for a long time; however, full understanding of this phenomenon in relation to the electronic structure has not been achieved. In this study, the recently observed qualitative differences between the platinum and gold compounds in the magnitude and the sign of spin-orbit-induced (SO) nuclear magnetic shielding at the vicinal light atom ((13)C, (15)N), σ(SO)(LA), are explained by the contractions of 6s and 6p atomic orbitals in Au complexes, originating in the larger Au nuclear charge and stronger scalar relativistic effects in gold complexes. This leads to the chemical activation of metal 6s and 6p atomic orbitals in Au complexes and their larger participation in bonding with the ligand, which modulates the propagation of metal-induced SO effects on the NMR signal of the LA via the Spin-Orbit/Fermi Contact (SO/FC) mechanism. The magnitude of the σ(SO)(LA) in these square-planar complexes can be understood on the basis of a balance between various metal-based 5d → 5d* and 6p → 6p* orbital magnetic couplings. The large and positive σ(SO)(LA) in platinum complexes is dominated by the shielding platinum-based 5d → 5d* magnetic couplings, whereas small or negative σ(SO)(LA) in gold complexes is related to the deshielding contribution of the gold-based 6p → 6p* magnetic couplings. Further, it is demonstrated that σ(SO)(LA) correlates quantitatively with the extent of M-LA electron sharing that is the covalence of the M-LA bond (characterized by the QTAIM delocalization index, DI). The present findings will contribute to further understanding of the origin and propagation of the relativistic effects influencing the experimental NMR parameters in heavy-element systems.

Electron density shift in imidazolium derivatives upon complexation with cucurbit[6]uril.

In this study, we have investigated the supramolecular interaction between series of 1-alkyl-3-methylimidazolium guests with variable alkyl substituent lengths and cucurbit[6]uril (CB6) in the solution and the solid state. Correct interpretation of (1)H NMR spectra was a key issue for determining the binding modes of the complexes in solution. Unusual chemical shifts of some protons in the (1)H NMR spectra were explained by the polarization of the imidazolium aromatic ring upon the complexation with the host. The formation of 1:1 complex between 1-ethyl-3-methylimidazolium and CB6 is in disagreement with previously reported findings describing an inclusion of two guest molecules in the CB6 cavity.

Mechanism of Spin-Orbit Effects on the Ligand NMR Chemical Shift in Transition-Metal Complexes: Linking NMR to EPR

Relativistic effects play an essential role in understanding the nuclear magnetic resonance (NMR) chemical shifts in heavy-atom compounds. Particularly interesting from the chemical point of view are the relativistic effects due to heavy atom (HA) on the NMR chemical shifts of the nearby light atoms (LA), referred to as the HALA effects. The effect of Spin-Orbit (SO) interaction originating from HA on the nuclear magnetic shielding at a neighboring LA, σ(SO), is explored here in detail for a series of d(6) complexes of iridium. Unlike the previous findings, the trends in σ(SO) observed in this study can be fully explained neither in terms of the s-character of the HA-LA bonding nor by trends in the energy differences between occupied and virtual molecular orbitals (MOs). Rather, the σ(SO) contribution to the total NMR shielding is found to be modulated by the d-orbital participation of the heavy atom (Ir) in the occupied and virtual spin-orbit active MOs, i.e., those which contribute significantly to the σ(SO). The correlation between the d-character of σ(SO)-active MOs and the size of the corresponding SO contribution to the nuclear magnetic shielding constant at LA is so tight that the magnitude of σ(SO) can be predicted in a given class of compounds on the basis of d-orbital character of relevant MO with relative error smaller than 15%. This correspondence is supported by an analogy between the perturbation theory expressions for the spin-orbit induced NMR σ-tensor and those for the EPR g-tensor as well as the A-tensor of the ligand. This correlation is demonstrated on a series of d(5) complexes of iridium. Thus, known qualitative relationships between electronic structure and EPR parameters can be newly applied to reproduce, predict, and understand the SO-induced contributions to NMR shielding constants of light atoms in heavy-atom compounds.