Islatravir Dimer: Crystal Form Dependence of a Radiation-Induced Degradation Product.

A rare example of crystal form-dependent, gamma radiation-induced degradation is presented. Islatravir is known to exist in several polymorphic forms, but only one of these forms shows the generation of a specific dimer degradation product under gamma irradiation. Extended gamma irradiation studies demonstrated that only one of the known crystalline forms shows an appreciable rate of dimer formation. Additionally, this dimer is not observed to form under other forced stress conditions. We present the structural elucidation of this dimer impurity and rationalize its form-dependent generation based on the analysis of the underlying crystal structure.

Leveraging ToF-SIMS imaging to investigate tenofovir disoproxil fumarate degradation at excipient interfaces in oral compressed tablets.

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging has been used to study the hydrolysis of tenofovir disoproxil fumarate (TDF) to tenofovir monosoproxil (TM) within an oral compressed tablet. The ToF-SIMS images displayed a heterogenous distribution of the matrix components. Evaluation of the TM distribution revealed that it was primarily co-localized with areas of higher excipient concentration pointing toward excipient driven degradation. To support these observations, a compatibility study of TDF with each tablet component was performed via liquid chromatography. The ToF-SIMS imaging and compatibility study indicated that the excipient, Avicel® PH-102, was the primary driver of TM formation in the tablet. The hydrolysis degradation mechanism within the tablet is further rationalized through discussion of chemical and physical properties of the matrix components. The sum of this work demonstrates a new analytical workflow for probing and understanding matrix driven degradation in oral compressed tablets utilizing ToF-SIMS imaging.

Exceptionally Complex Electronic Structures of Lanthanide Oxides and Small Molecules.

Lanthanide (Ln) oxide clusters and molecular systems provide a bottom-up look at the electronic structures of the bulk materials because of close parallels in the patterns of Ln 4fN subshell occupancy between the molecular and bulk Ln2O3 size limits. At the same time, these clusters and molecules offer a challenge to the theory community to find appropriate and robust treatments for the 4fN patterns across the Ln series. Anion photoelectron (PE) spectroscopy provides a powerful experimental tool for studying these systems, mapping the energies of the ground and low-lying excited states of the neutral relative to the initial anion state, providing spectroscopic patterns that reflect the Ln 4fN occupancy. In this Account, we review our anion PE spectroscopic and computational studies on a range of small lanthanide molecules and cluster species. The PE spectra of LnO- (Ln = Ce, Pr, Sm, Eu) diatomic molecules show spectroscopic signatures associated with detachment of an electron from what can be described as a diffuse Ln 6s-like orbital. While the spectra of all four diatomics share this common transition, the fine structure in the transition becomes more complex with increasing 4f occupancy. This effect reflects increased coupling between the electrons occupying the corelike 4f and diffuse 6s orbitals with increasing N. Understanding the PE spectra of these diatomics sets the stage for interpreting the spectra of polyatomic molecular and cluster species. In general, the results confirm that the partial 4fN subshell occupancy is largely preserved between molecular and bulk oxides and borides. However, they also suggest that surfaces and edges of bulk materials may support a low-energy, diffuse Ln 6s band, in contrast to bulk interiors, in which the 6s band is destabilized relative to the 5d band. We also identify cases in which the molecular Ln centers have 4fN+1 occupancy rather than bulklike 4fN, which results in weaker Ln-O bonding. Specifically, Sm centers in mixed Ce-Sm oxides or in SmxOy- (y ≤ x) clusters have this higher 4fN+1 occupancy. The PE spectra of these particular species exhibit a striking increase in the relative intensities of excited-state transitions with decreasing photon energy (resulting in lower photoelectron kinetic energy). This is opposite of what is expected on the basis of the threshold laws that govern photodetachment. We relate this phenomenon to strong electron-neutral interactions unique to these complex electronic structures. The time scale of the interaction, which shakes up the electronic configuration of the neutral, increases with decreasing electron momentum. From a computational standpoint, we point out that special care must be taken when considering Ln cluster and molecular systems toward the center of the Ln series (e.g., Sm, Eu), where treatment of electrons explicitly or using an effective core potential can yield conflicting results on competing subshell occupancies. However, despite the complex electronic structures associated with partially filled 4fN subshells, we demonstrate that inexpensive and tractable calculations yield useful qualitative insight into the general electronic structural features.

Mo Insertion into the H2 Bond in MoxSy- + H2 Reactions.

A combined experimental and computational study of H2 reactions with small 98MoxSy- clusters ranging from subsulfide (x ∼ y) to hypersulfide (y > 2x) is presented. Results suggest that the subsulfides react with H2 primarily by insertion of a more reduced Mo center into the H-H bond, forming a dihydride product. We find that this reaction occurs up to Mo oxidation states of +4. For the subsulfides containing a second metal in a sufficiently low oxidation state, a second insertion of H2 occurs, leading to a tetrahydride product. The reaction mechanisms of the sulfides are found to be very similar, albeit slightly higher energetically to those of the analogous oxosulfides that are also observed at low abundances in the experiments. In addition, the experimental results show an overall reduction of hypersulfides in the presence of H2, suggesting loss of H2S neutral molecules.

Electronic and Molecular Structures of the CeB6 Monomer.

The electronic and molecular structure of the CeB6 molecular unit has been probed by anion PE spectroscopy and DFT calculations to gain insight into structural and electronic relaxation on edge and corner sites of this ionic material. While boron in bulk lanthanide hexaboride materials assumes octahedral B63- units, the monomer assumes a less compact structure to delocalize the charge. Two competitive molecular structures were identified for the anion and neutral species, which include a boat-like structure and a planar or near-planar teardrop structure. Ce adopts different orbital occupancies in the two isomers; the boat-like structure has a 4f superconfiguration while the teardrop favors a 4f 6s occupancy. The B6 ligand in these structures carries a charge of -4 and -3, respectively. The teardrop structure, which was calculated to be isoenergetic with the boat structure, was most consistent with the experimental spectrum. B6-local orbitals crowd the energy window between the Ce 4f and 6s (HOMO) orbitals. A low-lying transition from the B-based orbitals is observed slightly less than 1 eV above the ground state. The results suggest that edge and corner conductivity involves stabilized, highly diffuse 6s orbitals or bands rather than the bulk-favored 5d band. High-spin and open-shell low-spin states were calculated to be very close in energy for both the anion and neutral, a characteristic that reflects how decoupled the 4f electron is from the B6 2p- and Ce 6s-based molecular orbitals.

Photoelectrons Are Not Always Quite Free.

The photoelectron spectra of Sm2O- obtained over a range of photon energies exhibit anomalous changes in relative excited-state band intensities. Specifically, the excited-state transition intensities increase relative to the transition to the neutral ground state with decreasing photon energy, the opposite of what is expected from threshold effects. This phenomenon was previously observed in studies on several Sm-rich homo- and heterolanthanide oxides collected with two different harmonic outputs of a Nd:YAG (2.330 and 3.495 eV) [ J. Chem. Phys. 2017, 146, 194310]. We relate these anomalous intensities to populations of ground and excited anionic and neutrals states through the inspection of time-dependent perturbation theory within the adiabatic and sudden limits and for the first time show that transition intensities in photoelectron spectroscopy have a deep significance in gauging participation from excited states. We believe our results will have significance in the study of other electron-rich systems that have especially high density of accessible spin states.

A Tale of Two Stabilities: How One Boron Atom Affects a Switch in Bonding Motifs in CeO2B x- ( x = 2, 3) Complexes.

Boronyl (B≡O) ligands have garnered much attention as isoelectronic and isolobal analogues of CO and CN-, yet successful efforts in synthesizing metal boronyl complexes remain scarce. Anion photoelectron (PE) spectroscopy and density functional theory calculations were employed to investigate two small CeO2B x- ( x = 2, 3) complexes generated from laser ablation of a mixed Ce/B pressed powder target. The spectra reveal markedly different bonding upon incorporation of an additional B atom. Most interestingly, CeO2B2- was found to have a Ce(I) center coordinated to two monoanionic boronyl ligands in a bent geometry. This result was unexpected as previous studies suggest electron-rich metals are most suitable for stabilizing such ligands; furthermore, it is one of the first examples of an experimental metal-polyboronyl complex. Introducing another boron atom, however, favors a much different geometry in which Ce(II) coordinates an O2B33- unit through both the O and B atoms, which was evident in the markedly different PE spectra.

Exotic electronic structures of SmxCe3-xOy (x = 0-3; y = 2-4) clusters and the effect of high neutral density of low-lying states on photodetachment transition intensities.

Lanthanide (Ln) oxide clusters have complex electronic structures arising from the partially occupied Ln 4f subshell. New anion photoelectron (PE) spectra of SmxCe3-xOy- (x = 0-3; y = 2-4) along with supporting results of density functional theory (DFT) calculations suggest interesting x and y-dependent Sm 4f subshell occupancy with implications for Sm-doped ionic conductivity of ceria, as well as the overall electronic structure of the heterometallic oxides. Specifically, the Sm centers in the heterometallic species have higher 4f subshell occupancy than the homonuclear Sm3Oy-/Sm3Oy clusters. The higher 4f subshell occupancy both weakens Sm-O bonds and destabilizes the 4f subshell relative to the predominantly O 2p bonding orbitals in the clusters. Parallels between the electronic structures of these small cluster systems with bulk oxides are explored. In addition, unusual changes in the excited state transition intensities, similar to those observed previously in the PE spectra of Sm2O- and Sm2O2- [J. O. Kafader et al., J. Chem. Phys. 146, 194310 (2017)], are also observed in the relative intensities of electronic transitions to excited neutral state bands in the PE spectra of SmxCe3-xOy- (x = 1-3; y = 2, 4). The new spectra suggest that the effect is enhanced with lower oxidation states and with an increasing number of Sm atoms, implying that the prevalence of electrons in the diffuse Sm 6s-based molecular orbitals and a more populated 4f subshell both contribute to this phenomenon. Finally, this work identifies challenges associated with affordable DFT calculations in treating the complex electronic structures exhibited by these systems, including the need for a more explicit treatment of strong coupling between the neutral and PE.

Insight into ethylene interactions with molybdenum suboxide cluster anions from photoelectron spectra of chemifragments.

Recent studies on reactions between MoxOy- cluster anions and H2O/C2H4 mixtures revealed a complex web of addition, hydrogen evolution, and chemifragmentation reactions, with chemifragments unambiguously connected to cluster reactions with C2H4. To gain insight into the molecular-scale interactions along the chemifragmentation pathways, the anion photoelectron (PE) spectra of MoC2H2-, MoC4H4-, MoOC2H2-, and MoO2C2H2- formed directly in MoxOy- + C2H4 (x > 1; y ≥ x) reactions, along with supporting CCSD(T) and density functional theory calculations, are presented and analyzed. The complexes have spectra that are all consistent with η2-acetylene complexes, though for all but MoC4H4-, the possibility that vinylidene complexes are also present cannot be definitively ruled out. Structures that are consistent with the PE spectrum of MoC2H2- differ from the lowest energy structure, suggesting that the fragment formation is under kinetic control. The PE spectrum of MoO2C2H2- additionally exhibits evidence that photodissociation to MoO2- + C2H2 may be occurring. The results suggest that oxidative dehydrogenation of ethylene is initiated by Lewis acid/base interactions between the Mo centers in larger clusters and the π orbitals in ethylene.

Molybdenum Oxide Cluster Anion Reactions with C2H4 and H2O: Cooperativity and Chemifragmentation.

To probe the mechanism of sacrificial reagents in catalytic processes, product distributions from MoxOy- clusters reacting individually with C2H4 and H2O are compared with those from reactions with a C2H4 + H2O mixture, with the thermodynamics explored computationally. These molecules were chosen to model production of H2 from H2O via H2O + C2H4 → H2 + CH3CHO, mediated by MoxOy- clusters. H2O is known to sequentially oxidize MoxOy- suboxide clusters while producing H2, resulting in less reactive clusters. MoxOy- (y ∼ x) clusters undergo chemi-fragmentation reactions with C2H4, with MoxOyC2Hz- complexes forming as the cluster oxidation state increases. Unique species observed in reactions with the C2H4 + H2O mixture, Mo2O5C2H2- and MoO3C2H4-, suggest that the internal energy gained in new Mo-O bond formation from oxidation by H2O opens additional reaction channels. C2H3O- is observed uniquely in reactions with the C2H4 + H2O mixture, giving indirect evidence of CH3CHO formation via the cluster mediated H2O + C2H4 → H2 + CH3CHO reaction; C2H3O- can form via dissociative electron attachment to CH3CHO. Calculations support mechanisms that invoke participation of two ethylene molecules on thermodynamically favorable pathways leading to experimentally observed products.

Ce in the +4 oxidation state: Anion photoelectron spectroscopy and photodissociation of small CexOyHz- molecules.

The anion photoelectron (PE) spectra of a range of small mono-cerium molecular species, along with the Ce2O4- and Ce3O6- stoichiometric clusters, are presented and analyzed with the support of density functional theory calculations. A common attribute of all of the neutral species is that the Ce centers in both the molecules and clusters are in the +4 oxidation state. In bulk ceria (CeO2), an unoccupied, narrow 4f band lies between the conventional valence (predominantly O 2p) and conduction (Ce 5d) bands. Within the CeO2-, CeO3H2-, and Ce(OH)4- series, the PE spectra and computational results suggest that the Ce 6s-based molecular orbital is the singly occupied HOMO in CeO2- but becomes destabilized as the Ce 4f-local orbital becomes stabilized with increasing coordination. CeO3-, a hyperoxide, undergoes photodissociation with 3.49 eV photon energy to form the stoichiometric neutral CeO2 and O-. In the CeO2-, Ce2O4- ,and Ce3O6- stoichiometric cluster series, the 6s destabilization with 4f stabilization is associated with increasing cluster size, suggesting that a bulk-like band structure may be realized with fairly small cluster sizes. The destabilization of the 6s-based molecular orbitals can be rationalized by their diffuse size relative to Ce-O bond lengths in a crystal structure, suggesting that 6s bands in the bulk may be relegated to the surface.

The electron shuffle: Cerium influences samarium 4f orbital occupancy in heteronuclear Ce-Sm oxide clusters.

The anion photoelectron (PE) spectra along with supporting results of density functional theory (DFT) calculations on SmO-, SmCeOy-, and Sm2Oy- (y = 1, 2) are reported and compared to previous results on CeO- [M. Ray et al., J. Chem. Phys. 142, 064305 (2015)] and Ce2Oy- (y = 1, 2) [J. O. Kafader et al., J. Chem. Phys. 145, 154306 (2016)]. Similar to the results on CexOy- clusters, the PE spectra of SmO-, SmCeOy-, and Sm2Oy- (y = 1, 2) all exhibit electronic transitions to the neutral ground state at approximately 1 eV e-BE. The Sm centers in SmO and Sm2O2 neutrals can be described with the 4f56s superconfiguration, which is analogous to CeO and Ce2O2 neutrals in which the Ce centers can be described with the 4f 6s superconfiguration (ZCe = ZSm - 4). The Sm center in CeSmO2, in contrast, has a 4f6 occupancy, while the Ce center maintains the 4f 6s superconfiguration. The less oxidized Sm centers in both Sm2O and SmCeO have 4f6 6s occupancies. The 4f6 subshell occupancy results in relatively weak Sm-O bond strengths. If this extra 4f occupancy also occurs in bulk Sm-doped ceria, it may play a role in the enhanced O2- ionic conductivity in Sm-doped ceria. Based on the results of DFT calculations, the heteronuclear Ce-Sm oxides have molecular orbitals that are distinctly localized Sm 4f, Sm 6s, Ce 4f, and Ce 6s orbitals. The relative intensity of two electronic bands in the PE spectrum of Sm2O- exhibits an unusual photon energy-dependence, and the PE spectrum of Sm2O2- exhibits a photon energy-dependent continuum signal between two electronic transitions. Several explanations, including the high magnetic moment of these suboxide species and the presence of low-lying quasi-bound anion states, are considered.

Molecular and electronic structures of cerium and cerium suboxide clusters.

The anion photoelectron (PE) spectra of Ce2Oy- (y = 1, 2), Ce3Oy- (y = 0-4), Ce4Oy- (y = 0-2), and Ce5Oy- (y = 1, 2) are reported and analyzed with supporting results from density functional theory calculations. The PE spectra all exhibit an intense electronic transition to the neutral ground state, all falling in the range of 0.7 to 1.1 eV electron binding energy, with polarization dependence consistent with detachment from diffuse Ce 6s-based molecular orbitals. There is no monotonic increase in electron affinity with increasing oxidation. A qualitative picture of how electronic structure evolves with an oxidation state emerges from comparison between the spectra and the computational results. The electronic structure of the smallest metallic cluster observed in this study, Ce3, is similar to the bulk structure in terms of atomic orbital occupancy (4f 5d2 6s). Initial cerium cluster oxidation involves largely ionic bond formation via Ce 5d and O 2p orbital overlap (i.e., larger O 2p contribution), with Ce-O-Ce bridge bonding favored over Ce=O terminal bond formation. With subsequent oxidation, the Ce 5d-based molecular orbitals are depleted of electrons, with the highest occupied orbitals described as diffuse Ce 6s based molecular orbitals. In the y ≤ (x + 1) range of oxidation states, each Ce center has a singly occupied non-bonding 4f orbital. The PE spectrum of Ce3O4- is unique in that it exhibits a single nearly vertical transition. The highly symmetric structure predicted computationally is the same structure determined from Ce3O4+ IR predissociation spectra [A. M. Burow et al., Phys. Chem. Chem. Phys. 13, 19393 (2011)], indicating that this structure is stable in -1, 0, and +1 charge states. Spectra of clusters with x ≥ 3 exhibit considerable continuum signal above the ground state transition; the intensity of the continuum signal decreases with increasing oxidation. This feature is likely the result of numerous quasi-bound anion states or two-electron transitions possible in molecules with abundant nearly degenerate partially occupied orbitals.

Mixed cerium-platinum oxides: Electronic structure of [CeO]Ptn (n = 1, 2) and [CeO2]Pt complex anions and neutrals.

The electronic structures of several small Ce-Pt oxide complexes were explored using a combination of anion photoelectron (PE) spectroscopy and density functional theory calculations. Pt and Pt2 both accept electron density from CeO diatomic molecules, in which the cerium atom is in a lower-than-bulk oxidation state (+2 versus bulk +4). Neutral [CeO]Pt and [CeO]Pt2 complexes are therefore ionic, with electronic structures described qualitatively as [CeO(+2)]Pt(-2) and [CeO(+)]Pt2 (-), respectively. The associated anions are described qualitatively as [CeO(+)]Pt(-2) and [CeO(+)]Pt2 (-2), respectively. In both neutrals and anions, the most stable molecular structures determined by calculations feature a distinct CeO moiety, with the positively charged Ce center pointing toward the electron rich Pt or Pt2 moiety. Spectral simulations based on calculated spectroscopic parameters are in fair agreement with the spectra, validating the computationally determined structures. In contrast, when Pt is coupled with CeO2, which has no Ce-localized electrons that can readily be donated to Pt, the anion is described as [CeO2]Pt(-). The molecular structure predicted computationally suggests that it is governed by charge-dipole interactions. The neutral [CeO2]Pt complex lacks charge-dipole stabilizing interactions, and is predicted to be structurally very different from the anion, featuring a single Pt-O-Ce bridge bond. The PE spectra of several of the complexes exhibit evidence of photodissociation with Pt(-) daughter ion formation. The electronic structures of these complexes are related to local interactions in Pt-ceria catalyst-support systems.

Photoelectron spectra of CeO(-) and Ce(OH)2 (-).

The photoelectron spectrum of CeO(-) exhibits what appears to be a single predominant electronic transition over an energy range in which numerous close-lying electronic states of CeO neutral are well known. The photoelectron spectrum of Ce(OH)2 (-), a molecule in which the Ce atom shares the same formal oxidation state as the Ce atom in CeO(-), also exhibits what appears to be a single transition. From the spectra, the adiabatic electron affinities of CeO and Ce(OH)2 are determined to be 0.936 ± 0.007 eV and 0.69 ± 0.03 eV, respectively. From the electron affinity of CeO, the CeO(-) bond dissociation energy was determined to be 7.7 eV, 0.5 eV lower than the neutral bond dissociation energy. The ground state orbital occupancies of both CeO(-) and Ce(OH)2 (-) are calculated to have 4f 6s(2) Ce(+) superconfigurations, with open-shell states having 4f5d6s superconfiguration predicted to be over 1 eV higher in energy. Low-intensity transitions observed at higher electron binding energies in the spectrum of CeO(-) are tentatively assigned to the (1)Σ(+) (Ω = 0) state of CeO with the Ce+26s2 superconfiguration.