The essential role of symmetry in understanding 3He chemical shifts in endohedral helium fullerenes.

The 3He atom is an excellent NMR probe, particularly when enclosed in endohedral helium fullerenes. The 3He chemical shift, δ(3He), in fullerenes spans a range from ca. -50 to +10 ppm, and changes sensitively between different cages, isomers, and external substituents. Reduction of the fullerenes to anions changes the δ(3He) dramatically and unexpectedly, particularly for the most symmetric and also the most abundant C60 and C70 cages. While the 3He atom is shielded by ∼43 ppm upon charging the He@C60 to He@C606-, it is correspondingly deshielded by ∼37 ppm in the He@C70/He@C706- pair. Here, we show that such puzzling differences in δ(3He) relate to the high symmetry of the host fullerene cages. While similar shielding is induced at the 3He atom by the core orbitals of different cages, the symmetry of the cage allows or quenches large paramagnetic, i.e., deshielding orbital interactions of frontier orbitals upon charging of the cage, which is directly responsible for the large observed chemical shift range of endohedral 3He.

Exact Two-Component TDDFT with Simple Two-Electron Picture-Change Corrections: X-ray Absorption Spectra Near L- and M-Edges of Four-Component Quality at Two-Component Cost.

X-ray absorption spectroscopy (XAS) has gained popularity in recent years as it probes matter with high spatial and elemental sensitivities. However, the theoretical modeling of XAS is a challenging task since XAS spectra feature a fine structure due to scalar (SC) and spin-orbit (SO) relativistic effects, in particular near L and M absorption edges. While full four-component (4c) calculations of XAS are nowadays feasible, there is still interest in developing approximate relativistic methods that enable XAS calculations at the two-component (2c) level while maintaining the accuracy of the parent 4c approach. In this article we present theoretical and numerical insights into two simple yet accurate 2c approaches based on an (extended) atomic mean-field exact two-component Hamiltonian framework, (e)amfX2C, for the calculation of XAS using linear eigenvalue and damped response time-dependent density functional theory (TDDFT). In contrast to the commonly used one-electron X2C (1eX2C) Hamiltonian, both amfX2C and eamfX2C account for the SC and SO two-electron and exchange-correlation picture-change (PC) effects that arise from the X2C transformation. As we demonstrate on L- and M-edge XAS spectra of transition metal and actinide compounds, the absence of PC corrections in the 1eX2C approximation results in a substantial overestimation of SO splittings, whereas (e)amfX2C Hamiltonians reproduce all essential spectral features such as shape, position, and SO splitting of the 4c references in excellent agreement, while offering significant computational savings. Therefore, the (e)amfX2C PC correction models presented here constitute reliable relativistic 2c quantum-chemical approaches for modeling XAS.

Enzyme-Catalyzed Polymerization Process: A Novel Approach to the Preparation of Polyaniline Colloidal Dispersions with an Immunomodulatory Effect.

A green, nature-friendly synthesis of polyaniline colloidal particles based on enzyme-assisted oxidation of aniline with horseradish peroxidase and chitosan or poly(vinyl alcohol) as steric stabilizers was successfully employed. Physicochemical characterization revealed formation of particles containing the polyaniline emeraldine salt and demonstrated only a minor effect of polymer stabilizers on particle morphology. All tested colloidal particles showed in vitro antioxidation activity determined via scavenging of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. In vitro, they were able to reduce oxidative stress and inhibit the production of reactive oxygen species by neutrophils and inflammatory cytokines by macrophages. The anti-inflammatory effect observed was related to their antioxidant activity, especially in the case of neutrophils. The particles can thus be especially advantageous as active components of biomaterials modulating the early stages of inflammation. In addition to the immunomodulatory effect, the presence of intrinsically conducting polyaniline can impart cell-instructive properties to the particles. The approach to particle synthesis that we employed─an original one using environmentally friendly and biocompatible horseradish peroxidase─represents a smart way of preparing conducting particles with unique properties, which can be further modified by the stabilizers used.

Accurate X-ray Absorption Spectra near L- and M-Edges from Relativistic Four-Component Damped Response Time-Dependent Density Functional Theory.

The simulation of X-ray absorption spectra requires both scalar and spin-orbit (SO) relativistic effects to be taken into account, particularly near L- and M-edges where the SO splitting of core p and d orbitals dominates. Four-component Dirac-Coulomb Hamiltonian-based linear damped response time-dependent density functional theory (4c-DR-TDDFT) calculates spectra directly for a selected frequency region while including the relativistic effects variationally, making the method well suited for X-ray applications. In this work, we show that accurate X-ray absorption spectra near L2,3- and M4,5-edges of closed-shell transition metal and actinide compounds with different central atoms, ligands, and oxidation states can be obtained by means of 4c-DR-TDDFT. While the main absorption lines do not change noticeably with the basis set and geometry, the exchange-correlation functional has a strong influence with hybrid functionals performing the best. The energy shift compared to the experiment is shown to depend linearly on the amount of Hartee-Fock exchange with the optimal value being 60% for spectral regions above 1000 eV, providing relative errors below 0.2% and 2% for edge energies and SO splittings, respectively. Finally, the methodology calibrated in this work is used to reproduce the experimental L2,3-edge X-ray absorption spectra of [RuCl2(DMSO)2(Im)2] and [WCl4(PMePh2)2], and resolve the broad bands into separated lines, allowing an interpretation based on ligand field theory and double point groups. These results support 4c-DR-TDDFT as a reliable method for calculating and analyzing X-ray absorption spectra of chemically interesting systems, advance the accuracy of state-of-the art relativistic DFT approaches, and provide a reference for benchmarking more approximate techniques.

Behaviour of Titanium Dioxide Particles in Artificial Body Fluids and Human Blood Plasma.

The growing application of materials containing TiO2 particles has led to an increased risk of human exposure, while a gap in knowledge about the possible adverse effects of TiO2 still exists. In this work, TiO2 particles of rutile, anatase, and their commercial mixture were exposed to various environments, including simulated gastric fluids and human blood plasma (both representing in vivo conditions), and media used in in vitro experiments. Simulated body fluids of different compositions, ionic strengths, and pH were used, and the impact of the absence or presence of chosen enzymes was investigated. The physicochemical properties and agglomeration of TiO2 in these media were determined. The time dependent agglomeration of TiO2 related to the type of TiO2, and mainly to the type and composition of the environment that was observed. The presence of enzymes either prevented or promoted TiO2 agglomeration. TiO2 was also observed to exhibit concentration-dependent cytotoxicity. This knowledge about TiO2 behavior in all the abovementioned environments is critical when TiO2 safety is considered, especially with respect to the significant impact of the presence of proteins and size-related cytotoxicity.

Experimental and Theoretical Evidence of Spin-Orbit Heavy Atom on the Light Atom 1 H†NMR Chemical Shifts Induced through H⋠⋠⋠I- Hydrogen Bond.

Spin-orbit (SO) heavy-atom on the light-atom (SO-HALA) effect is the largest relativistic effect caused by a heavy atom on its light-atom neighbors, leading, for example, to unexpected NMR chemical shifts of 1 H, 13 C, and 15 N nuclei. In this study, a combined experimental and theoretical evidence for the SO-HALA effect transmitted through hydrogen bond is presented. Solid-state NMR data for a series of 4-dimethylaminopyridine salts containing I- , Br- and Cl- counter ions were obtained experimentally and by theoretical calculations. A comparison of the experimental chemical shifts with those calculated by a standard DFT methodology without the SO contribution to the chemical shifts revealed a remarkable error of the calculated proton chemical shift of a hydrogen atom that is in close contact with the iodide anion. The addition of the relativistic SO correction in the calculations significantly improves overall agreement with the experiment and confirms the propagation of the SO-HALA effect through hydrogen bonds.

Experimental and Theoretical Evidence of Spin-Orbit Heavy Atom on the Light Atom 1 H†NMR Chemical Shifts Induced through H⋠⋠⋠I- Hydrogen Bond.

Invited for the cover of this issue is the group of Michal Straka and Martin Dracínský (IOCB Prague, Czech Academy of Sciences). The image depicts a neutron star, which is used to represent the relativistic effects between a heavy element and a hydrogen atom reported in this work. Read the full text of the article at 10.1002/chem.202001532.

Towards Accurate Predictions of Proton NMR Spectroscopic Parameters in Molecular Solids.

The factors contributing to the accuracy of quantum-chemical calculations for the prediction of proton NMR chemical shifts in molecular solids are systematically investigated. Proton chemical shifts of six solid amino acids with hydrogen atoms in various bonding environments (CH, CH2 , CH3 , OH, SH and NH3 ) were determined experimentally using ultra-fast magic-angle spinning and proton-detected 2D NMR experiments. The standard DFT method commonly used for the calculations of NMR parameters of solids is shown to provide chemical shifts that deviate from experiment by up to 1.5 ppm. The effects of the computational level (hybrid DFT functional, coupled-cluster calculation, inclusion of relativistic spin-orbit coupling) are thoroughly discussed. The effect of molecular dynamics and nuclear quantum effects are investigated using path-integral molecular dynamics (PIMD) simulations. It is demonstrated that the accuracy of the calculated proton chemical shifts is significantly better when these effects are included in the calculations.

Relativity or aromaticity? A first-principles perspective of chemical shifts in osmabenzene and osmapentalene derivatives.

We have studied the magnetic response properties and aromaticity of osmium metallacycles by means of scalar-relativistic (1c) and fully relativistic (4c) density functional theory computations. For osmabenzene, whose aromatic character is controversial, a topological analysis of the current density has revealed the presence of a unique σ-type Craig-Möbius magnetic aromaticity. We show that the partially filled osmium valence shell induces a large paratropic current, which may interfere with certain methods commonly used to analyze aromaticity, in particular NICS. Further, we show that the extreme deshielding of the light atoms in the vicinity of the osmium atoms in osmapentalene derivatives is not a consequence of aromaticity but can be explained by paramagnetic couplings between σOs-C bonding orbitals and the π*Os orbitals. We demonstrate that variations in the orientation of the induced magnetic currents through the molecule dictates the alternating signs of the spin-orbit contribution to the NMR chemical shift.

Selectively Oxidized Cellulose with Adjustable Molecular Weight for Controlled Release of Platinum Anticancer Drugs.

The synthesis of selectively oxidized cellulose, 2,3-dicarboxycellulose (DCC), is optimized for preparation of highly oxidized material for biological applications, which includes control over the molecular weight of the product during its synthesis. Conjugates of DCC and cisplatin simultaneously offer a very high drug binding efficiency (>90%) and drug loading capacity (up to 50 wt %), while retaining good aqueous solubility. The adjustable molecular weight of the DCC together with variances in drug feeding ratio allows to optimize cisplatin release profiles from delayed (<2% of cisplatin released during 6 h) to classical burst release with more than 60% of cisplatin released after 24 h. The release rates are also pH-dependent (up to 2 times faster release at pH 5.5 than at pH 7.4), which allows to exploit the acidic nature of tumor microenvironment. Extensive in vitro studies were performed on eight different cell lines for two cisplatin-DCC conjugates with different release profiles. In comparison with free cisplatin, both cisplatin-DCC conjugates demonstrated considerably lower cytotoxicity toward healthy cells. Conjugates with burst release profiles were found more effective against prostate cell lines, while DCC conjugates with slower release were more cytotoxic against ovarian and lung carcinoma cell lines. In vivo studies indicated a significantly longer survival rate, a reduction in tumor volume, and a higher accumulation of platinum in tumors of mice treated with the cisplatin-DCC conjugate in comparison to those treated by free cisplatin.

Spectroscopic and Computational Evidence of Intramolecular AuI ⋠⋠⋠H+ -N Hydrogen Bonding.

Despite substantial evidence of short Au⋅⋅⋅H-X contacts derived from a number of X-ray structures of AuI compounds, the nature of AuI ⋅⋅⋅H bonding in these systems has not been clearly understood. Herein, we present the first spectroscopic evidence for an intramolecular AuI ⋅⋅⋅H+ -N hydrogen bond in a [Cl-Au-L]+ complex, where L is a protonated N-heterocyclic carbene. The complex was isolated in the gas phase and characterized with helium-tagging infrared photodissociation (IRPD) spectra, in which H+ -N-mode-derived bands evidence the intramolecular AuI ⋅⋅⋅H+ -N bond. Quantum chemical calculations reproduce the experimental IRPD spectra and allow to characterize the intramolecular Au⋅⋅⋅H+ -N bonding with a short rAu⋅⋅⋅H distance of 2.17 Šand an interaction energy of approximately -10 kcal mol-1 . Various theoretical descriptors of chemical bonding calculated for the Au⋅⋅⋅H+ -N interaction provide strong evidence for a hydrogen bond of moderate strength.

Reactive Dimerization of an N-Heterocyclic Plumbylene: C-H Activation with PbII.

The N-heterocyclic plumbylene [Fe{(η5 -C5 H4 )NSiMe3 }2 Pb:] is in equilibrium with an unprecedented dimer in solution, whose formation involves the cleavage of a strong C-H bond and concomitant formation of a Pb-C and an N-H bond. According to a mechanistic DFT assessment, dimer formation does not involve direct PbII insertion into a cyclopentadienyl C-H bond, but is best described as an electrophilic substitution. The bulkier plumbylene [Fe{(η5 -C5 H4 )NSitBuMe2 }2 Pb:] shows no dimerization, but compensates its electrophilicity by the formation of an intramolecular Fe-Pb bond.

Gas-phase fragmentation of 1-adamantylbisimidazolium salts and their complexes with cucurbit[7]uril studied using selectively 2 H-labeled guest molecules.

RATIONALE: Bisimidazolium salts (BIMs) represent an interesting family of ditopic ligands that are used in the construction of supramolecular systems with hosts based on cyclodextrins or cucurbit[n]urils. Understanding the fragmentation mechanism of individual BIMs and how this mechanism changes after complexation with cucurbit[n]urils can bring new insight into the intrinsic host-guest relationship, thereby allowing utilization of mass spectrometry to describe binding behavior. METHODS: Selectively 2 H-labeled bisimidazolium salts were prepared and fully characterized by spectroscopic methods. All MSn experiments were conducted in the positive-ion mode using an electrospray ionization (ESI) ion-trap mass spectrometer. The structures of the proposed fragments were supported by theoretical optimizations performed at the B3LYP/6-31G(d) level of density functional theory (DFT) using the Spartan'14 program. RESULTS: Using selectively deuterium-labeled isotopologues of two adamantylated bisimidazolium salts and DFT calculations, we describe the fragmentation pathways of bisimidazolium salts. The release of two important adamantane moieties, [C11 H17 ]+ and C11 H16 , from M2+ was determined, although the former was strongly preferred. In contrast, when M2+ was complexed with CB7, the neutral loss of the C11 H16 fragment was favored. The fragmentation pattern strongly depended on the steric hindrance of the M2+ guest against slippage of the CB7 unit over the guest molecular axle. CONCLUSIONS: The structures of two adamantane-based fragments and the mechanisms of their formation were rationalized. Two distinct geometric arrangements for the adamantane cage inside the CB7 cavity were hypothesized to explain the differences in the fragmentation patterns for guests with minimal, moderate, and high steric hindrance. This finding brings new insight into the understanding of intrinsic behavior of the adamantane-based guests inside the CB7 cavity.

Properties of the Only Thorium Fullerene, Th@C84, Uncovered.

Only a single thorium fullerene, Th@C84, has been reported to date (Akiyama, K.; et al. J. Nucl. Radiochem. Sci. 2002, 3, 151-154). Although the system was characterized by UV-vis and XANES (X-ray absorption near edge structure) spectra, its structure and properties remain unknown. In this work we used the density functional calculations to identify molecular and electronic structure of the Th@C84. Series of molecular structures satisfying the ThC84 stoichiometric formula were studied comprising 24 IPR and 110 non-IPR Th@C84 isomers as well as 9 ThC2@C82 IPR isomers. The lowest energy structure is Th@C84-Cs(10) with the singlet ground state. Its predicted electronic absorption spectra are in agreement with the experimentally observed ones. The bonding between the cage and Th was characterized as polar covalent with Th in formal oxidation state IV. The NMR chemical shifts of Th@C84-Cs(10) were predicted to guide the future experimental efforts in identification of this compound.

The influence of Mg2+ coordination on 13C and 15N chemical shifts in CKI1RD protein domain from experiment and molecular dynamics/density functional theory calculations.

Sequence dependence of (13) C and (15) N chemical shifts in the receiver domain of CKI1 protein from Arabidopsis thaliana, CKI1RD , and its complexed form, CKI1RD •Mg(2+), was studied by means of MD/DFT calculations. MD simulations of a 20-ns production run length were performed. Nine explicitly hydrated structures of increasing complexity were explored, up to a 40-amino-acid structure. The size of the model necessary depended on the type of nucleus, the type of amino acid and its sequence neighbors, other spatially close amino acids, and the orientation of amino acid NH groups and their surface/interior position. Using models covering a 10 and a 15 Å environment of Mg(2+), a semi-quantitative agreement has been obtained between experiment and theory for the V67-I73 sequence. The influence of Mg(2+) binding was described better by the 15 Å as compared to the 10 Å model. Thirteen chemical shifts were analyzed in terms of the effect of Mg(2+) insertion and geometry preparation. The effect of geometry was significant and opposite in sign to the effect of Mg(2+) binding. The strongest individual effects were found for (15) N of D70, S74, and V68, where the electrostatics dominated; for (13) Cß of D69 and (15) N of K76, where the influences were equal, and for (13) Cα of F72 and (13) Cß of K76, where the geometry adjustment dominated. A partial correlation between dominant geometry influence and torsion angle shifts upon the coordination has been observed.

High-Frequency 1H NMR Chemical Shifts of SnII and PbII Hydrides Induced by Relativistic Effects: Quest for PbII Hydrides.

The role of relativistic effects on 1H NMR chemical shifts of SnII and PbII hydrides is investigated by using fully relativistic DFT calculations. The stability of possible PbII 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 PbII. Such high-frequency 1H NMR chemical shifts of PbII 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 PbII compounds. Modulation of spin-orbit relativistic contribution to 1H NMR chemical shift is found to be important also in the experimentally known SnII 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 SnII and PbII hydrides, their application for structural investigation is suggested.

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

The (13)C and (29)Si 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 (13)C and over 1000 ppm for (29)Si, outside the typical experimental NMR chemical-shift ranges for a given type of nuclei. The large (13)C and (29)Si NMR chemical shifts are ascribed to sizable relativistic spin-orbit effects, which can amount to more than 200 ppm for (13)C and more than 1000 ppm for (29)Si, values unexpected for diamagnetic compounds of the main group elements. The origin of the vast spin-orbit contributions to the (13)C and (29)Si 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.

Unwilling U-U bonding in U2@C80: cage-driven metal-metal bonds in di-uranium fullerenes.

Endohedral actinide fullerenes are rare and a little is known about their molecular properties. Here we characterize the U2@C80 system, which was recently detected experimentally by means of mass spectrometry (Akiyama et al., JACS, 2001, 123, 181). Theoretical calculations predict a stable endohedral system, (7)U2@C80, derived from the C80:7 IPR fullerene cage, with six unpaired electrons. Bonding analysis reveals a double ferromagnetic (one-electron-two-center) U-U bond at an rU-U distance of 3.9 Å. This bonding is realized mainly via U(5f) orbitals. The U-U interaction inside the cage is estimated to be about -18 kcal mol(-1). U-U bonding is further studied along the U2@Cn (n = 60, 70, 80, 84, 90) series and the U-U bonds are also identified in U2@C70 and U2@C84 systems at rU-U∼ 4 Å. It is found that the character of U-U bonding depends on the U-U distance, which is dictated by the cage type. A concept of unwilling metal-metal bonding is suggested: uranium atoms are strongly bound to the cage and carry a positive charge. Pushing the U(5f) electron density into the U-U bonding region reduces electrostatic repulsion between enclosed atoms, thus forcing U-U bonds.

Structure, solvent, and relativistic effects on the NMR chemical shifts in square-planar transition-metal complexes: assessment of DFT approaches.

The role of various factors (structure, solvent, and relativistic treatment) was evaluated for square-planar 4d and 5d transition-metal complexes. The DFT method for calculating the structures was calibrated using a cluster approach and compared to X-ray geometries, with the PBE0 functional (def2-TZVPP basis set) providing the best results, followed closely by the hybrid TPSSH and the MN12SX functionals. Calculations of the NMR chemical shifts using the two-component (2c, Zeroth-Order Regular Approximation as implemented in the ADF package) and four-component (4c, Dirac-Coulomb as implemented in the ReSpect code) relativistic approaches were performed to analyze and demonstrate the importance of solvent corrections (2c) as well as a proper treatment of relativistic effects (4c). The importance of increased exact-exchange admixture in the functional (here PBE0) for reproducing the experimental data using the current implementation of the 2c approach is partly rationalized as a compensation for the missing exchange-correlation response kernel. The kernel contribution was identified to be about 15-20% of the spin-orbit-induced NMR chemical shift, ΔδSO, which roughly corresponds to an increase in ΔδSO introduced by the artificially increased exact-exchange admixture in the functional. Finally, the role of individual effects (geometry, solvent, relativity) in the NMR chemical shift is discussed in selected complexes. Although a fully relativistic DFT approach is still awaiting the implementation of GIAOs for hybrid functionals and an implicit solvent model, it nevertheless provides reliable NMR chemical shift data at an affordable computational cost. It is expected to outperform the 2c approach, in particular for the calculation of NMR parameters in heavy-element compounds.