Guided Ion Beam Studies of the Thorium Monocarbonyl Cation Bond Dissociation Energy and Theoretical Unveiling of Different Isomers of [Th,O,C]+ and Their Rearrangement Mechanism.

Threshold collision-induced dissociation (TCID) of the thorium monocarbonyl cation, ThCO+, with xenon is performed using a guided ion beam tandem mass spectrometer. The only product observed is Th+ resulting from loss of the CO ligand. Analysis of the kinetic energy-dependent cross sections for this CID reaction yields the first experimental determination of the bond dissociation energy (BDE) of Th+-CO at 0 K as 0.94 ± 0.06 eV. Calculated BDEs at the CCSD(T) level of theory with cc-pVXZ (X = T and Q) basis sets and a complete basis set (CBS) extrapolation are in good agreement with the experimental result. The Feller-Peterson-Dixon composite coupled-cluster methodology was also applied on both ThCO+ and ThCO, with contributions up to CCSDT(Q) and a four-component treatment of spin-orbit coupling effects. The final 0 K Th+-CO BDE of 0.94 ± 0.04 eV is in excellent agreement with the current experimental result. The ionization energy of ThCO, as well as the atomization energies and heats of formation for both ThCO and ThCO+, is reported at this same level of theory. Complete potential energy profiles of both quartet and doublet spin are also constructed to elucidate the mechanism for the formation and interconversion of different isomers of [Th,O,C]+. Chemical bonding patterns in low-lying states of ThCO+ and potential energy curves for ThCO+ dissociation are also investigated.

Molecular insights into the improved clinical performance of PEGylated interferon therapeutics: a molecular dynamics perspective.

PEGylation is a widely adopted process to covalently attach a polyethylene glycol (PEG) polymer to a protein drug for the purpose of optimizing drug clinical performance. While the outcomes of PEGylation in imparting pharmacological advantages have been examined through experimental studies, the underlying molecular mechanisms remain poorly understood. Using interferon (IFN) as a representative model system, we carried out comparative molecular dynamics (MD) simulations of free PEGx, apo-IFN, and PEGx-IFN (x = 50, 100, 200, 300) to characterize the molecular-level changes in IFN introduced by PEGylation. The simulations yielded molecular evidence directly linked to the improved protein stability, bioavailability, retention time, as well as the decrease in protein bioactivity with PEG conjugates. Our results indicate that there is a tradeoff between the benefits and costs of PEGylation. The optimal PEG chain length used in PEGylation needs to strike a good balance among the competing factors and maximizes the overall therapeutic efficacy of the protein drug. We anticipate the study will have a broad implication for protein drug design and development, and provide a unique computational approach in the context of optimizing PEGylated protein drug conjugates.

Spectroscopic and theoretical studies of ThCl and ThCl.

The electronic structures of ThCl and ThCl+ have been examined using laser induced fluorescence and two-photon ionization techniques. Rotationally resolved spectra, combined with the predictions from relativistic electronic structure calculations, show that the ground state of the neutral molecule is Th+(7s26d)Cl-, X2Δ3/2. Dispersed fluorescence spectra for ThCl revealed the ground state vibrational levels v = 0-10 and low energy electronic states that also originate from the atomic ion 7s26d configuration. Pulsed field ionization-zero kinetic energy photoelectron spectroscopy established an ionization energy (IE) for ThCl of 51 344(5) cm-1, and the ThCl+ vibrational term energies of the v = 1-3 levels. The zero-point level of the first electronically excited state was found at 949(2) cm-1. Comparisons with high-level theoretical results indicate that the ground and excited states are Th2+(7s6d)Cl- X3Δ1 and Th2+(7s2)Cl- Σ+1, respectively. Relativistic coupled cluster composite thermochemistry calculations yielded an IE within 1.2 kcal/mol of experiment and a bond dissociation energy (118.3 kcal/mol) in perfect agreement with previous experiments.

Bond energies of ThO(+) and ThC(+): A guided ion beam and quantum chemical investigation of the reactions of thorium cation with O2 and CO.

Kinetic energy dependent reactions of Th(+) with O2 and CO are studied using a guided ion beam tandem mass spectrometer. The formation of ThO(+) in the reaction of Th(+) with O2 is observed to be exothermic and barrierless with a reaction efficiency at low energies of k/kLGS = 1.21 ± 0.24 similar to the efficiency observed in ion cyclotron resonance experiments. Formation of ThO(+) and ThC(+) in the reaction of Th(+) with CO is endothermic in both cases. The kinetic energy dependent cross sections for formation of these product ions were evaluated to determine 0 K bond dissociation energies (BDEs) of D0(Th(+)-O) = 8.57 ± 0.14 eV and D0(Th(+)-C) = 4.82 ± 0.29 eV. The present value of D0 (Th(+)-O) is within experimental uncertainty of previously reported experimental values, whereas this is the first report of D0 (Th(+)-C). Both BDEs are observed to be larger than those of their transition metal congeners, TiL(+), ZrL(+), and HfL(+) (L = O and C), believed to be a result of lanthanide contraction. Additionally, the reactions were explored by quantum chemical calculations, including a full Feller-Peterson-Dixon composite approach with correlation contributions up to coupled-cluster singles and doubles with iterative triples and quadruples (CCSDTQ) for ThC, ThC(+), ThO, and ThO(+), as well as more approximate CCSD with perturbative (triples) [CCSD(T)] calculations where a semi-empirical model was used to estimate spin-orbit energy contributions. Finally, the ThO(+) BDE is compared to other actinide (An) oxide cation BDEs and a simple model utilizing An(+) promotion energies to the reactive state is used to estimate AnO(+) and AnC(+) BDEs. For AnO(+), this model yields predictions that are typically within experimental uncertainty and performs better than density functional theory calculations presented previously.

Gas Phase Properties of MX2 and MX4 (X = F, Cl) for M = Group 4, Group 14, Cerium, and Thorium.

Structures, vibrational frequencies, and heats of formation were predicted for MX4 and both singlet and triplet states of MX2 (M = group 4, group 14, Ce, and Th; X = F and Cl) using the Feller-Peterson-Dixon composite electronic structure approach based on coupled cluster CCSD(T) calculations extrapolated to the complete basis set limit with additional corrections including spin orbit effects. The spin-orbit corrections are not large but need to be included for chemical accuracy of ±1 kcal/mol. The singlet-triplet splittings were calculated for the dihalides and all compounds have singlet ground states except for the dihalides of Ti, Zr, and Ce which have triplet ground states. The calculated heats of formation are in good agreement with the available experimental data. Our predictions suggest that the experimental heats of formation need to be revised for a number of tetrahalides: TiF4, HfF4, PbF4, PbCl4, and ThCl4 as well as a number of dihalides: GeF2, SnF2, PbF2, TiF2, and TiCl2. The calculated heats of formation were used to predict various thermodynamic properties including average M-F and M-Cl bond dissociation energies and the reaction energies for MX2 + X2 → MX4. Edge inversion barriers were predicted. The calculated edge inversion barriers for the tetrafluorides show that the barriers for the group 14 tetrafluorides decrease with increasing atomic number, the group 4 barriers are ∼50 kcal/mol and CeF4 and ThF4 have inversion barriers of ∼25 kcal/mol.