Applying Unconventional Spectroscopies to the Single-Molecule Magnets,Co(PPh3)2X2 (X=Cl,Br, I): Unveiling Magnetic Transitions and Spin-Phonon Coupling

Large separation of magnetic levels and slow relaxation in metal complexes are desirable properties of single-molecule magnets (SMMs). Spin-phonon coupling (interactions of magnetic levels with phonons) is ubiquitous, leading to magnetic relaxation and loss of memory in SMMs and quantum coherence in qubits. Direct observation of magnetic transitions and spin-phonon coupling in molecules is challenging. We have found that far-IR magnetic spectra (FIRMS) of Co(PPh₃)₂X₂ ( Co-X ; X=Cl, Br, I) reveal rarely observed spin-phonon coupling as avoided crossings between magnetic and u-symmetry phonon transitions. Inelastic neutron scattering (INS) gives phonon spectra. Calculations using VASP and phonopy programs gave phonon symmetries and movies. Magnetic transitions among zero-field split (ZFS) levels of the S=3/2 electronic ground state were probed by INS, high-frequency and -field EPR (HFEPR), FIRMS, and frequency-domain FT terahertz EPR (FD-FT THz-EPR), giving magnetic excitation spectra and determining ZFS parameters (D, E) and g values. Ligand-field theory (LFT) was used to analyze earlier electronic absorption spectra and give calculated ZFS parameters matching those from the experiments. DFT calculations also gave spin densities in Co-X , showing that the larger Co(II) spin density in a molecule, the larger its ZFS magnitude. The current work reveals dynamics of magnetic and phonon excitations in SMMs. Studies of such couplings in the future would help to understand how spin-phonon coupling may lead to magnetic relaxation and develop guidance to control such coupling.     

Towards the stable chelation of radium for biomedical applications with an 18-membered macrocyclic ligand

Targeted alpha therapy is an emerging strategy for the treatment of disseminated cancer. [²²³Ra]RaCl₂ is the only clinically approved alpha particle-emitting drug, and it is used to treat castrate-resistant prostate cancer bone metastases, to which [²²³Ra]Ra²⁺ localizes. To specifically direct [²²³Ra]Ra²⁺ to non-osseous disease sites, chelation and conjugation to a cancer-targeting moiety is necessary. Although previous efforts to stably chelate [²²³Ra]Ra²⁺ for this purpose have had limited success, here we report a biologically stable radiocomplex with the 18-membered macrocyclic chelator macropa. Quantitative labeling of macropa with [²²³Ra]Ra²⁺ was accomplished within 5 min at room temperature with a radiolabeling efficiency of >95%, representing a significant advancement over conventional chelators such as DOTA and EDTA, which were unable to completely complex [²²³Ra]Ra²⁺ under these conditions. [²²³Ra][Ra(macropa)] was highly stable in human serum and exhibited dramatically reduced bone and spleen uptake in mice in comparison to bone-targeted [²²³Ra]RaCl₂, signifying that [²²³Ra][Ra(macropa)] remains intact in vivo. Upon conjugation of macropa to a single amino acid β-alanine as well as to the prostate-specific membrane antigen-targeting peptide DUPA, both constructs retained high affinity for ²²³Ra, complexing >95% of Ra²⁺ in solution. Furthermore, [²²³Ra][Ra(macropa-β-alanine)] was rapidly cleared from mice and showed low ²²³Ra bone absorption, indicating that this conjugate is stable under biological conditions. Unexpectedly, this stability was lost upon conjugation of macropa to DUPA, which suggests a role of targeting vectors in complex stability in vivo for this system. Nonetheless, our successful demonstration of efficient radiolabeling of the β-alanine conjugate with ²²³Ra and its subsequent stability in vivo establishes for the first time the possibility of delivering [²²³Ra]Ra²⁺ to metastases outside of the bone using functionalized chelators, marking a significant expansion of the therapeutic utility of this radiometal in the clinic.

The therapeutic alpha-emitter ²²³Ra can be stably complexed in vivo, creating opportunities for the development of targeted radiopharmaceutical agents with this radionuclide.     

Equivariant Chow Ring and Chern Classes of Wonderful Symmetric Varieties of Minimal Rank

We describe the equivariant Chow ring of the wonderful compactification X of a symmetric space of minimal rank, via restriction to the associated toric variety Y. Also, we show that the restrictions to Y of the tangent bundle T _X and its logarithmic analogue S _X decompose into a direct sum of line bundles. This yields closed formulas for the equivariant Chern classes of T _X and S _X , and, in turn, for the Chern classes of reductive groups considered by Kiritchenko.     

Effect of the plasma location on the deflagration-to-detonation transition of a hydrogen–air flame enhanced by nanosecond repetitively pulsed discharges

This work presents a method for using nanosecond repetitively pulsed (NRP) plasma discharges for accelerating a propagating flame such that the deflagration-to-detonation transition occurs. A strategy is developed for bringing the location of the plasma near the tube wall and, thus, reducing the presence of the electrodes in the combustion tube as well as presenting a configuration in which cooling of the electrodes is viable for practical applications. Time-of-flight measurements were used in combination with energy deposition measurements and high-speed OH*-chemiluminescence imagery to investigate the flame acceleration process. For stoichiometric hydrogen–air flames, successful transition to detonation was achieved by applying a burst of 110 pulses at 100 kHz, with energies as low as 10 mJ per pulse. This was also achieved when plasma discharges were applied in the vicinity of the wall. Two enhancement mechanisms for flame acceleration were identified. The essential role of shock–flame interaction was established as being the main mechanism for flame acceleration when the discharges are located near the wall. This work presents an effective alternative that allows for NRP discharges to be applied near the wall while successfully maintaining a promising success rate for detonation transition.     

UnyLinker dimer impurity characterization and process improvement

Herein, we describe the isolation and characterization of a UnyLinker dimer which, if left uncontrolled, can become incorporated in oligonucleotide products. The dimer is formed as a result of an unusual intermolecular osmium-catalyzed etherification. We demonstrate that by simply replacing H₂O₂ as the co-oxidant with NMO, none of the UnyLinker dimer impurity is formed.     

Textile‐based Electrochemical Sensing: Effect of Fabric Substrate and Detection of Nitroaromatic Explosives

This study examines the influence of textile substrates upon the behavior of wearable screen‐printed electrodes and demonstrates the attractive sensing properties of these sensors towards the detection of nitroaromatic explosives. Compared to electrodes printed on common cotton or polyester substrates, GORE‐TEX‐based electrochemical sensors display reproducible background cyclic voltammograms, reflecting the excellent water‐repellant properties of the GORE‐TEX fabric. The wetting properties of different printed textile electrodes are elucidated using contact angle measurements. The influence of laundry washing and mechanical stress is explored. The GORE‐TEX‐based printed electrodes exhibit favorable detection of 2,4‐dinitrotoluene (DNT) and 2,4,6‐trinitrotoluene (TNT) explosives, including rapid detection of DNT vapor.     

The applicability of three-dimensional aromaticity in BiSn(n)- Zintl analogues

Three-dimensional aromaticity is shown to play a role in the stability of deltahedral Zintl clusters and here we examine the connection between aromaticity and stability. In order to gain further insight, we have studied Zintl analogs comprised of bismuth doped tin clusters with photoelectron spectroscopy and theoretical methods. To assign aromaticity, we examine the ring currents induced around the cage by using the nucleus independent chemical shift. In the current study, BiSn(4)(-) is a stable cluster and fits aromatic criteria, while BiSn(5)(-) is found to fit antiaromatic criteria and has reduced stability. The more stable clusters exhibit an aromatic character which originates from weakly interacting s-states and bonding orbitals parallel to the surface of the cluster, while nonbonding lone pairs perpendicular to the surface of the cluster account for antiaromaticity and reduced stability. The effect of three-dimensional aromaticity on the electronic structure does not result in degeneracies, so the resulting variations in stability are smaller than those seen in conventional aromaticity.     

Context-dependent effects of asparagine glycosylation on Pin WW folding kinetics and thermodynamics

Asparagine glycosylation is one of the most common and important post-translational modifications of proteins in eukaryotic cells. N-glycosylation occurs when a triantennary glycan precursor is transferred en bloc to a nascent polypeptide (harboring the N-X-T/S sequon) as the peptide is cotranslationally translocated into the endoplasmic reticulum (ER). In addition to facilitating binding interactions with components of the ER proteostasis network, N-glycans can also have intrinsic effects on protein folding by directly altering the folding energy landscape. Previous work from our laboratories (Hanson et al. Proc. Natl. Acad. Sci. U.S.A. 2009, 109, 3131-3136; Shental-Bechor, D.; Levy, Y. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 8256-8261) suggested that the three sugar residues closest to the protein are sufficient for accelerating protein folding and stabilizing the resulting structure in vitro; even a monosaccharide can have a dramatic effect. The highly conserved nature of these three proximal sugars in N-glycans led us to speculate that introducing an N-glycosylation site into a protein that is not normally glycosylated would stabilize the protein and increase its folding rate in a manner that does not depend on the presence of specific stabilizing protein-saccharide interactions. Here, we test this hypothesis experimentally and computationally by incorporating an N-linked GlcNAc residue at various positions within the Pin WW domain, a small β-sheet-rich protein. The results show that an increased folding rate and enhanced thermodynamic stability are not general, context-independent consequences of N-glycosylation. Comparison between computational predictions and experimental observations suggests that generic glycan-based excluded volume effects are responsible for the destabilizing effect of glycosylation at highly structured positions. However, this reasoning does not adequately explain the observed destabilizing effect of glycosylation within flexible loops. Our data are consistent with the hypothesis that specific, evolved protein-glycan contacts must also play an important role in mediating the beneficial energetic effects on protein folding that glycosylation can confer.