Biocompatible Xanthine-Quadruplex Scaffold for Ion-Transporting DNA Channels

Molecular dynamics simulations and adaptive biasing force analysis of the quadruplex DNA dynamics in an explicit solvent reveal fundamentally different mechanisms of Na⁺ transport in xanthine- and guanine-based DNA systems. The barrier to the transport of K⁺ through the xanthine-based quadruplex is significantly lower than those reported for the guanine-based analogs

High-Frequency ¹H NMR Chemical Shifts of Sn^II and Pb^II Hydrides Induced by Relativistic Effects: Quest for Pb^II Hydrides

The role of relativistic effects on ¹H NMR chemical shifts of Sn^II and Pb^II hydrides is investigated by using fully relativistic DFT calculations. The stability of possible Pb^II hydride isomers is studied together with their ¹H NMR chemical shifts, which are predicted in the high-frequency region, up to 90 ppm. These ¹H signals are dictated by sizable relativistic contributions due to spin–orbit coupling at the heavy atom and can be as large as 80 ppm for a hydrogen atom bound to Pb^II. Such high-frequency ¹H NMR chemical shifts of Pb^II hydride resonances cannot be detected in the ¹H NMR spectra with standard experimental setup. Extended ¹H NMR spectral ranges are thus suggested for studies of Pb^II compounds. Modulation of spin–orbit relativistic contribution to ¹H NMR chemical shift is found to be important also in the experimentally known Sn^II hydrides. Because the ¹H NMR chemical shifts were found to be rather sensitive to the changes in the coordination sphere of the central metal in both Sn^II and Pb^II hydrides, their application for structural investigation is suggested

High-Frequency ¹³C and ²⁹Si NMR Chemical Shifts in Diamagnetic Low-Valence Compounds of Tl^I and Pb^II: Decisive Role of Relativistic Effects

The ¹³C and ²⁹Si NMR signals of ligand atoms directly bonded to Tl^I or Pb^II heavy-element centers are predicted to resonate at very high frequencies, up to 400 ppm for ¹³C and over 1000 ppm for ²⁹Si, outside the typical experimental NMR chemical-shift ranges for a given type of nuclei. The large ¹³C and ²⁹Si NMR chemical shifts are ascribed to sizable relativistic spin–orbit effects, which can amount to more than 200 ppm for ¹³C and more than 1000 ppm for ²⁹Si, values unexpected for diamagnetic compounds of the main group elements. The origin of the vast spin–orbit contributions to the ¹³C and ²⁹Si NMR shifts is traced to the highly efficient 6p → 6p* metal-based orbital magnetic couplings and related to the 6p orbital-based bonding together with the low-energy gaps between the occupied and virtual orbital subspaces in the subvalent Tl^I and Pb^II compounds. New NMR spectral regions for these compounds are suggested based on the fully relativistic density functional theory calculations in the Dirac–Coulomb framework carefully calibrated on the experimentally known NMR data for Tl^I and Pb^II complexes

Platinum-Modified Adenines: Unprecedented Protonation Behavior Revealed by NMR Spectroscopy and Relativistic Density-Functional Theory Calculations

Two novel Pt^IV complexes of aromatic cytokinins with possible antitumor properties were prepared by reaction of selected aminopurines with K₂PtCl₆. The structures of both complexes, 9-[6-(benzylamino)­purine] pentachloroplatinate (IV) and 9-[6-(furfurylamino)­purine] pentachloroplatinate (IV), were characterized in detail by using two-dimensional NMR spectroscopy (¹H, ¹³C, ¹⁵N, and ¹⁹⁵Pt) in solution and CP/MAS NMR techniques in the solid state. We report for the first time the X-ray structure of a nucleobase adenine derivative coordinated to Pt^IV via the N9 atom. The protonation equilibria for the complexes in solution were characterized by using NMR spectroscopy (isotropic chemical shifts and indirect nuclear spin–spin coupling constants) and the structural conclusions drawn from the NMR analysis are supported by relativistic density-functional theory (DFT) calculations. Because of the presence of the Pt atom, hybrid GGA functionals and scalar-relativistic and spin–orbit corrections were employed for both the DFT calculations of the molecular structure and particularly for the NMR chemical shifts. In particular, the populations of the N7-protonated and neutral forms of the complexes in solution were characterized by correlating the experimental and the DFT-calculated NMR chemical shifts. In contrast to the chemical exchange process involving the N7–H group, the hydrogen atom at N3 was determined to be unexpectedly rigid, probably because of the presence of the stabilizing intramolecular interaction N3–H···Cl. The described methodology combining the NMR spectroscopy and relativistic DFT calculations can be employed for characterizing the tautomeric and protonation equilibria in a large family of transition-metal-modified purine bases

Comment on “Some Unexpected Behavior of the Adsorption of Alkali Metal Ions onto the Graphene Surface under the Effect of External Electric Field”

Comment on “Some Unexpected Behavior of the Adsorption of Alkali Metal Ions onto the Graphene Surface under the Effect of External Electric Field

Intermolecular Interactions in Crystalline Theobromine as Reflected in Electron Deformation Density and ¹³C NMR Chemical Shift Tensors

An understanding of the role of intermolecular interactions in crystal formation is essential to control the generation of diverse crystalline forms which is an important concern for pharmaceutical industry. Very recently, we reported a new approach to interpret the relationships between intermolecular hydrogen bonding, redistribution of electron density in the system, and NMR chemical shifts (Babinský et al. <i>J. Phys. Chem. A</i>, <b>2013</b>, <i>117</i>, 497). Here, we employ this approach to characterize a full set of crystal interactions in a sample of anhydrous theobromine as reflected in ¹³C NMR chemical shift tensors (CSTs). The important intermolecular contacts are identified by comparing the DFT-calculated NMR CSTs for an isolated theobromine molecule and for clusters composed of several molecules as selected from the available X-ray diffraction data. Furthermore, electron deformation density (EDD) and shielding deformation density (SDD) in the proximity of the nuclei involved in the proposed interactions are calculated and visualized. In addition to the recently reported observations for hydrogen bonding, we focus here particularly on the stacking interactions. Although the principal relations between the EDD and CST for hydrogen bonding (HB) and stacking interactions are similar, the real-space consequences are rather different. Whereas the C–H···X hydrogen bonding influences predominantly and significantly the in-plane principal component of the ¹³C CST perpendicular to the HB path and the CO···H hydrogen bonding modulates both in-plane components of the carbonyl ¹³C CST, the stacking modulates the out-of-plane electron density resulting in weak deshielding (2–8 ppm) of both in-plane principal components of the CST and weak shielding (∼ 5 ppm) of the out-of-plane component. The hydrogen-bonding and stacking interactions may add to or subtract from one another to produce total values observed experimentally. On the example of theobromine, we demonstrate the power of this approach to identify and classify the intermolecular forces that govern the packing motifs in crystals and modulate the NMR CSTs

Origin of the Conformational Modulation of the ¹³C NMR Chemical Shift of Methoxy Groups in Aromatic Natural Compounds

The interpretation of nuclear magnetic resonance (NMR) parameters is essential to understanding experimental observations at the molecular and supramolecular levels and to designing new and more efficient molecular probes. In many aromatic natural compounds, unusual ¹³C NMR chemical shifts have been reported for out-of-plane methoxy groups bonded to the aromatic ring (∼62 ppm as compared to the typical value of ∼56 ppm for an aromatic methoxy group). Here, we analyzed this phenomenon for a series of aromatic natural compounds using Density Functional Theory (DFT) calculations. First, we checked the methodology used to optimize the structure and calculate the NMR chemical shifts in aromatic compounds. The conformational effects of the methoxy group on the ¹³C NMR chemical shift then were interpreted by the Natural Bond Orbital (NBO) and Natural Chemical Shift (NCS) approaches, and by excitation analysis of the chemical shifts, breaking down the total nuclear shielding tensor into the contributions from the different occupied orbitals and their magnetic interactions with virtual orbitals. We discovered that the atypical ¹³C NMR chemical shifts observed are not directly related to a different conjugation of the lone pair of electrons of the methoxy oxygen with the aromatic ring, as has been suggested. Our analysis indicates that rotation of the methoxy group induces changes in the virtual molecular orbital space, which, in turn, correlate with the predominant part of the contribution of the paramagnetic deshielding connected with the magnetic interactions of the BD_CMet–H→BD*_CMet–OMet orbitals, resulting in the experimentally observed deshielding of the ¹³C NMR resonance of the out-of-plane methoxy group

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 d⁶ 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 <i>active</i> 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 d⁵ 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

Origin of the Thermodynamic Stability of the Polymorph IV of Crystalline Barbituric Acid: Evidence from Solid-State NMR and Electron Density Analyses

In this contribution, the origin of the stability of the polymorph IV (enol form) of crystalline barbituric acid relative to the polymorph II (keto form) is investigated using solid-state NMR spectroscopy and electron density analysis. Electron density analysis reveals differences in the nature of the intermolecular contacts in the different polymorphs of barbituric acid. Comparing the properties of hypothetical single molecules of barbituric acid with cluster models shows that the electronic and magnetic properties of polymorphs of barbituric acid can be employed to measure the strengths of the intermolecular interactions. Changes in the magnitudes of the NMR chemical shift tensors are also shown to be parallel to the intermolecular delocalization index of Quantum Theory of Atoms in Molecules, which measures the covalency of an intermolecular interaction

Through-Space Paramagnetic NMR Effects in Host–Guest Complexes: Potential Ruthenium(III) Metallodrugs with Macrocyclic Carriers

The potential of paramagnetic ruthenium­(III) compounds for use as anticancer metallodrugs has been investigated extensively during the past several decades. However, the means by which these ruthenium compounds are transported and distributed in living bodies remain relatively unexplored. In this work, we prepared several novel ruthenium­(III) compounds with the general structure Na⁺[<i>trans</i>-Ru^IIICl₄(DMSO)­(L)]⁻ (DMSO = dimethyl sulfoxide), where L stands for pyridine or imidazole linked with adamantane, a hydrophobic chemophore. The supramolecular interactions of these compounds with macrocyclic carriers of the cyclodextrin (CD) and cucurbit­[<i>n</i>]­uril (CB) families were investigated by NMR spectroscopy, X-ray diffraction analysis, isothermal titration calorimetry, and relativistic DFT methods. The long-range hyperfine NMR effects of the paramagnetic guest on the host macrocycle are related to the distance between them and their relative orientation in the host–guest complex. The CD and CB macrocyclic carriers being studied in this account can be attached to a vector that attracts the drug-carrier system to a specific biological target and our investigation thus introduces a new possibility in the field of targeted delivery of anticancer metallodrugs based on ruthenium­(III) compounds