Comparison of the structural, electrochemical, and spectroscopic properties of two cryptates of trivalent uranium.

We describe a study of the influence of cryptand denticity on the structural, electronic, and electrochemical properties of UIII-containing cryptates. Two cryptands (2.2.2 and 2.2.1) are reported. The cryptand with the smaller denticity leads to negative electrochemical potentials and shorter bond lengths that are consistent with a better fit for UIII than the larger cryptand. These studies provide insight into the rational design of cryptand-based ligands for trivalent uranium.

Expanding the Coordination of f-Block Metals with Tris[2-(2-methoxyethoxy)ethyl]amine: From Molecular Complexes to Cage-like Structures.

Low-valent f-block metals have intrinsic luminescence, electrochemical, and magnetic properties that are modulated with ligands, causing the coordination chemistry of these metals to be imperative to generating critical insights needed to impact modern applications. To this end, we synthesized and characterized a series of twenty-seven complexes of f-metal ions including EuII, YbII, SmII, and UIII and hexanuclear clusters of LaIII and CeIII to study the impact of tris[2-(2-methoxyethoxy)ethyl]amine, a flexible acyclic analogue of the extensively studied 2.2.2-cryptand, on the coordination chemistry and photophysical properties of low-valent f-block metals. We demonstrate that the flexibility of the ligand enables luminescence tunability over a greater range than analogous cryptates of EuII in solution. Furthermore, the ligand also displays a variety of binding modes to f-block metals in the solid state that are inaccessible to cryptates of low-valent f-block metals. In addition to serving as a ligand for f-block metals of various sizes and oxidation states, tris[2-(2-methoxyethoxy)ethyl]amine also deprotonates water molecules coordinated to trivalent triflate salts of f-block metal ions, enabling the isolation of hexanuclear clusters containing either LaIII or CeIII. The ligand was also found to bind more tightly to YbII and UIII in the solid state compared to 2.2.2-cryptand, suggesting that it can play a role in the isolation of other low-valent f-block metals such CfII, NpIII, and PuIII. We expect that our findings will inspire applications of tris[2-(2-methoxyethoxy)ethyl]amine in the design of light-emitting diodes and the synthesis of extremely reducing divalent f-block metal complexes that are of interest for a wide range of applications.

Cryptands on a Solid Support for the Separation of Europium from Gadolinium.

With the great demand for europium in green-energy technologies comes the need for innovative methods to isolate the elements. We introduce a solid-liquid extraction method using a 2.2.2-cryptand-modified solid support to separate europium from gadolinium using their differences in electrochemical potential. The method overcomes challenges associated with the separation of those two ions that have similar coordination chemistry in the +3 oxidation state. A competitive adsorption study in the cryptand system between EuII/EuIII and GdIII shows greater affinity for EuII relative to GdIII. After separation from GdIII, Eu was released by oxidizing EuII to EuIII with 99.3% purity. The purity of separated Eu is unaffected by pH between pH 3.0 and 5.5. Overall, we demonstrate that by modifying a solid support with 2.2.2-cryptand, divalent europium can be separated from trivalent gadolinium based on the differences of affinities of 2.2.2-cryptand for the two ions.

Partial Parasagittal Patellectomy in Dogs: A Retrospective Case Series of 19 Dogs.

OBJECTIVE: The aim of this study was to describe partial parasagittal patellectomy for the surgical management of patellar luxation, including surgical technique, proposed indications, complications, and outcomes in a cohort of dogs. STUDY DESIGN: This is a single-center retrospective clinical case series. METHODS: Medical records (2019-2020) of dogs presenting for patellar luxation were reviewed. Clinical signs, luxation direction and grade, preoperative imaging and intraoperative findings, and complications were retrospectively retrieved. Owners were contacted via questionnaire for medium- and long-term follow-up. RESULTS: A total of 24 stifles in 19 dogs met the inclusion criteria. Intraoperative minor complications occurred in four stifles. A single minor complication occurred postoperatively with no major complications. Increased thickness and radiographic attenuation of the patellar ligament were noted in 14 stifles at radiographic reassessment. Re-luxation was not encountered, with long-term owner-assessed outcome as good to excellent in all cases. CONCLUSION: Partial parasagittal patellectomy, used in conjunction with block recession trochleoplasty and tibial tuberosity transposition, provided reliable resolution of patellar luxation in canine stifles with grade 2 or 3 luxation where width mismatch between the patella and the trochlea was noted intraoperatively. Long-term outcome appears to be good to excellent with a low rate of complication.

3D-printed, patient-specific cutting guides improve femoral and tibial cut alignment in canine total knee replacement.

OBJECTIVES: The purpose of this cadaveric study was to determine whether patient-specific guides (PSGs) improve the accuracy of tibial and femoral cut alignment in canine total knee replacement (TKR), as compared with generic cutting guides. STUDY DESIGN: Original research. ANIMALS: Sixteen pelvic limbs from skeletally mature medium- to large-breed canine cadavers. METHODS: Specimens were randomly allocated to one of two groups (PSG or Generic; N = 8/group). In the Generic group, femoral and tibial ostectomies were made using the standard canine TKR femoral cutting blocks and tibial alignment guide. In the PSG group, the cuts were made using a series of custom 3D-printed cutting guides. "Planned" and "actual" tibial and femoral cut alignments were compared in the frontal and sagittal planes, and errors were calculated by subtracting actual from planned values. RESULTS: Use of 3D-printed PSGs improved tibial cut alignment in the frontal plane but not the sagittal plane. PSGs also improved the alignment of the cranial and distal femoral ostectomies but did not impact varus-valgus alignment. CONCLUSIONS: These findings support the use of PSGs for TKR in dogs. Clinical trials are now needed to determine whether the benefits of PSGs translate into measurable improvements in joint function and implant longevity. CLINICAL SIGNIFICANCE: PSGs have the potential to improve femoral and tibial component alignment in canine TKR.

Toward quantification of hypoxia using fluorinated EuII/III-containing ratiometric probes.

Hypoxia is a prognostic biomarker of rapidly growing cancers, where the extent of hypoxia is an indication of tumor progression and prognosis; therefore, hypoxia is also used for staging while performing chemo- and radiotherapeutics for cancer. Contrast-enhanced MRI using EuII-based contrast agents is a noninvasive method that can be used to map hypoxic tumors, but quantification of hypoxia using these agents is challenging due to the dependence of signal on the concentration of both oxygen and EuII. Here, we report a ratiometric method to eliminate concentration dependence of contrast enhancement of hypoxia using fluorinated EuII/III-containing probes. We studied three different EuII/III couples of complexes containing 4, 12, or 24 fluorine atoms to balance fluorine signal-to-noise ratio with aqueous solubility. The ratio between the longitudinal relaxation time (T1) and 19F signal of solutions containing different ratios of EuII- and EuIII-containing complexes was plotted against the percentage of EuII-containing complexes in solution. We denote the slope of the resulting curves as hypoxia indices because they can be used to quantify signal enhancement from Eu, that is related to oxygen concentration, without knowledge of the absolute concentration of Eu. This mapping of hypoxia was demonstrated in vivo in an orthotopic syngeneic tumor model. Our studies significantly contribute toward improving the ability to radiographically map and quantify hypoxia in real time, which is critical to the study of cancer and a wide range of diseases.

Outersphere Approach to Increasing the Persistance of Oxygen-Sensitive Europium(II)-Containing Contrast Agents for Magnetic Resonance Imaging with Perfluorocarbon Nanoemulsions toward Imaging of Hypoxia.

Radiographic mapping of hypoxia is needed to study a wide range of diseases. Complexes of Eu(II) are a promising class of molecules to fit this need, but they are generally limited by their rapid oxidation rates in vivo. Here, a perfluorocarbon-nanoemulsion perfused with N2 , forms an interface with aqueous layers to hinder oxidation of a new perfluorocarbon-soluble complex of Eu(II). Conversion of the perfluorocarbon solution of Eu(II) into nanoemulsions results in observable differences between reduced and oxidized forms by magnetic resonance imaging both in vitro and in vivo. Oxidation in vivo occurrs over a period of ≈30 min compared to <5 min for a comparable Eu(II)-containing complex without nanoparticle interfaces. These results represent a critical step toward delivery of Eu(II)-containing complexes in vivo for the study of hypoxia.

Three-Dimensional Morphometry of the Canine Pelvis: Implications for Total Hip Replacement Surgery.

OBJECTIVES: Two-dimensional measurements of acetabular geometry are widely used for the assessment of acetabular component orientation following total hip replacement (THR). With the increasing availability of computed tomography scans, there is an opportunity to develop three-dimensional (3D) planning to improve surgical accuracy. The aim of this study was to validate a 3D workflow for measuring angles of lateral opening (ALO) and version, and to establish reference values for dogs. METHODS: Pelvic computed tomography scans were obtained from 27 skeletally mature dogs with no radiographic evidence of hip joint pathology. Patient-specific 3D models were built, and ALO and version angles were measured for both acetabula. The validity of the technique was determined by calculating intra-observer coefficient of variation (CV, %). Reference ranges were calculated and data from left and right hemipelves were compared using a paired t-test and symmetry index. RESULTS: Measurements of acetabular geometry were highly repeatable (intra-observer CV 3.5-5.2%, inter-observer CV 3.3-5.2%). Mean (± standard deviation) values for ALO and version angle were 42.9 degrees (± 4.0 degrees) and 27.2 degrees (± 5.3 degrees) respectively. Left-right measurements from the same dog were symmetrical (symmetry index 6.8 to 11.1%) and not significantly different. CONCLUSIONS: Mean values of acetabular alignment were broadly similar to clinical THR guidelines (ALO of 45 degrees, version angle of 15-25 degrees), but the wide variation in angle measurements highlights the potential need for patient-specific planning to reduce the risk of complications such as luxation.

Systemic Delivery of Divalent Europium from Ligand Screening with Implications to Direct Imaging of Hypoxia.

Hypoxia is a hallmark of many diseases, including cancer, arthritis, heart and kidney diseases, and diabetes, and it is often associated with disease aggressiveness and poor prognosis. Consequently, there is a critical need for imaging hypoxia in a noninvasive and direct way to diagnose, stage, and monitor the treatment and development of new therapies for these diseases. Eu-containing contrast agents for magnetic resonance imaging have demonstrated potential for in vivo imaging of hypoxia via changes in metal oxidation state from +2 to +3, but rapid oxidation in blood limits EuII-containing complexes to studies compatible with direct injection to sites. Here, we report a new EuII-containing complex that persists in oxygenated environments and is capable of persisting in blood long enough for imaging by magnetic resonance imaging. We describe the screening of a library of ligands that led to the discovery of the complex as well as a pH-dependent mechanism that hinders oxidation to enable usefulness in vivo. These studies of the first divalent lanthanide complex that persists in oxygenated solutions open the door to the use of EuII-based contrast agents for imaging hypoxia in a wide range of diseases.

Properties of Amine-Containing Ligands That Are Necessary for Visible-Light-Promoted Catalysis with Divalent Europium.

We describe a study of the influence of amine-containing ligands on the photoredox-relevant properties of EuII toward the rational design of EuII-containing catalysts for visible-light-promoted photoredox reactions. We report our observations of the effects of the degree of functionalization of amines, denticity, and macrocylic ligands on the absorbance of EuII. Ligands that contain secondary amines bathochromically shift the absorbance of EuCl2 relative to ligands that contain primary or tertiary amines. Similarly, ligands of larger denticity have a larger bathochromic shift of the absorbance than ligands of smaller denticity. We observed that macrocyclic ligands have a larger effect on the absorbance of EuCl2 than nonmacrocyclic ligands. Also, we report the photoredox reactivity of four new EuII-containing complexes. These observations are potentially influential in understanding the ligand properties that promote the use of EuII in visible-light-promoted photoredox catalysis.

Development of a Highly Selective Ni(II) Chelator in Aqueous Solution.

The design, synthesis, and characterization of a novel Ni(II) chelator SG-20 is reported. SG-20 is selective in binding to Ni(II) versus other metal ions including Cu(II), Fe(II), Co(II), and Zn(II). At pH = 7.1, SG-20 binds Ni(II) with a Kd = 7.0 ± 0.4 µM. Job analysis indicates that SG-20 binds to both Ni(II) and Cu(II) with a 1:1 stoichiometry. Affinity of SG-20 for Ni(II) is pH dependent and decreases upon lowering to pH 4.0. A green solid was isolated from the reaction of SG-20 with NiCl2·6H2O in MeOH and characterized by X-ray photoelectron spectroscopy (XPS), electronic absorption and infrared (IR) spectroscopies, and mass spectrometry. Collectively, XPS and IR analysis revealed Ni-N and Ni-O interactions and a shift in C-O asymmetric and symmetric stretches consistent with Ni binding. Attempts to crystalize a mononuclear complex were unsuccessful, likely due to the Ni-SG-20 complex being in equilibrium with higher order species in solution. However, reaction of SG-20 with NiCl2·6H2O in water followed by slow evaporation yielded green crystals that were characterized by electronic absorption spectroscopy (λmax = 260 nm) and X-ray crystallography. These analyses revealed that SG-20 supports formation of a complex cluster containing six SG-20 ligands, 15 Ni(II), and three Na(I) centers, with two distinct types of Ni atoms in its outer and inner core. The nine Ni atoms present in the inner core were bound by oxo and carbonate bridges, whereas the six Ni atoms present in its outer shell were bound to N, O, and S donor atoms derived from SG-20. Overall, X-ray crystallographic analysis revealed that two chelator arms of SG-20 bind to one Ni(II) ion with an axial aqua ligand, whereas the third arm is free to interact with Ni ions within the central cluster, supporting the goal of Ni capture.

A Mouse Holder for Awake Functional Imaging in Unanesthetized Mice: Applications in 31P Spectroscopy, Manganese-Enhanced Magnetic Resonance Imaging Studies, and Resting-State Functional Magnetic Resonance Imaging.

Anesthesia is often used in preclinical imaging studies that incorporate mouse or rat models. However, multiple reports indicate that anesthesia has significant physiological impacts. Thus, there has been great interest in performing imaging studies in awake, unanesthetized animals to obtain accurate results without the confounding physiological effects of anesthesia. Here, we describe a newly designed mouse holder that is interfaceable with existing MRI systems and enables awake in vivo mouse imaging. This holder significantly reduces head movement of the awake animal compared to previously designed holders and allows for the acquisition of improved anatomical images. In addition to applications in anatomical T2-weighted magnetic resonance imaging (MRI), we also describe applications in acquiring 31P spectra, manganese-enhanced magnetic resonance imaging (MEMRI) transport rates and resting-state functional magnetic resonance imaging (rs-fMRI) in awake animals and describe a successful conditioning paradigm for awake imaging. These data demonstrate significant differences in 31P spectra, MEMRI transport rates, and rs-fMRI connectivity between anesthetized and awake animals, emphasizing the importance of performing functional studies in unanesthetized animals. Furthermore, these studies demonstrate that the mouse holder presented here is easy to construct and use, compatible with standard Bruker systems for mouse imaging, and provides rigorous results in awake mice.

Dual-Mode Tumor Imaging Using Probes That Are Responsive to Hypoxia-Induced Pathological Conditions.

Hypoxia in solid tumors is associated with poor prognosis, increased aggressiveness, and strong resistance to therapeutics, making accurate monitoring of hypoxia important. Several imaging modalities have been used to study hypoxia, but each modality has inherent limitations. The use of a second modality can compensate for the limitations and validate the results of any single imaging modality. In this review, we describe dual-mode imaging systems for the detection of hypoxia that have been reported since the start of the 21st century. First, we provide a brief overview of the hallmarks of hypoxia used for imaging and the imaging modalities used to detect hypoxia, including optical imaging, ultrasound imaging, photoacoustic imaging, single-photon emission tomography, X-ray computed tomography, positron emission tomography, Cerenkov radiation energy transfer imaging, magnetic resonance imaging, electron paramagnetic resonance imaging, magnetic particle imaging, and surface-enhanced Raman spectroscopy, and mass spectrometric imaging. These overviews are followed by examples of hypoxia-relevant imaging using a mixture of probes for complementary single-mode imaging techniques. Then, we describe dual-mode molecular switches that are responsive in multiple imaging modalities to at least one hypoxia-induced pathological change. Finally, we offer future perspectives toward dual-mode imaging of hypoxia and hypoxia-induced pathophysiological changes in tumor microenvironments.

Solid-state and solution-phase characterization of SmII-aza[2.2.2]cryptate and its methylated analogue.

Two new SmII-azacryptates are reported that differ in steric hindrance and Lewis basicity of donor atoms. The sterically hindered complex has a smaller coordination number and a more negative electrochemical potential than the complex with less steric hindrance.

Owner-reported outcome measures in veterinary care for companion animal orthopedic patients: An international online survey of veterinarians' expectations and practices.

OBJECTIVE: To report veterinarians' familiarity with and perceptions of owner/observer-reported outcome measures (OROMs) and their applications in routine clinical practice. STUDY DESIGN: Cross-sectional online survey. ANIMALS OR SAMPLE POPULATION: A total of 441 veterinarians with a caseload of companion animal orthopedic patients. METHODS: Respondents answered questions regarding their familiarity with and application of OROMs. Respondents provided opinions on statements related to reasons for using or not using OROMs in routine clinical practice, prerequisites to implement OROMs in routine clinical practice, and whether they would implement OROMs in routine clinical practice if adequate tools/technologies were available. RESULTS: Most (293/441, 66.4%) respondents felt familiarity with at least one OROM. Only 17.5% (77 out of the 440 answering the question about the application of OROMs) applied OROMs in routine clinical practice. The two main reasons for not using OROMs in routine clinical practice were the lack of opportunity/feasibility and the lack sufficient information/knowledge/experiences. User-friendliness, time efficiency, and interpretability were considered the most important prerequisites for implementing OROMs in routine clinical practice. If adequate tools/technologies were available, 266/439 (60.6%) respondents indicated that they would definitely implement OROMs in routine clinical practice. CONCLUSION: Although most respondents were familiar with at least one OROM, fewer than one-fifth applied them in routine clinical practice. Most respondents were willing to implement OROMs in routine clinical practice if adequate tools/technologies were available. CLINICAL SIGNIFICANCE: Our results justify further investigations to improve the application of OROMs in routine clinical practice in veterinary care of companion animal orthopedic patients.

Identification of seven-coordinate LnIII ions in a LnIII[15-MCFe III N(shi)-5](OAc)2Cl species crystallized from methanol and pyridine.

The title metallacrown (MC) complexes LnIII[15-MCFeIIIN(shi)-5](OAc)2CI(C5H5N)6 (Ln1), where OAc- is acetate, shi3- is salicylhydroximate, and Ln = Gd and Dy, were synthesized via a self-assembly reaction in methanol and pyridine. Single crystals were grown using slow evaporation and characterized using X-ray diffraction. Seven-coordinate capped octahedron geometries were observed for the lanthanide ion in both complexes, which is uncommon for trivalent lanthanide species. The 15-MC-5 is a ruffled metallacrown archetype similar to previously reported mixed-valent manganese metallacrowns.

Near-Infrared Lanthanide-Based Emission from Fused Bis[Ln(III)/Zn(II) 14-metallacrown-5] Coordination Compounds.

A set of (Ln[14-MCZn(II)N(quinHA)-5])2Ln2Zn2(quinHA)2(ph)2(Hph)4(OH)8(H2O)4 metallacrowns (Ln-1, Ln = Tb, Gd, or Yb; H2quinHA = quinaldic hydroxamic acid, H2ph = phthalic acid) have been synthesized via solution-state self-assembly. The metallacrowns possess an uncommon topology within the metallacrown family where two rarely seen 14-metallacrown-5 moieties are fused by a Yb2Zn2(quinHA)2 bridge. Moreover, Yb-1 analyzed in the solid state exhibits a characteristic near-infrared luminescence signal arising from Yb3+ 2F5/2→2F7/2 transition despite the proximity of high energy O-H oscillators.

Hexa-µ-acetato-chlorido-(µ-N,2-dioxodo-benzene-1-carboximidato)-µ3-oxido-tetra-iron(III)-water (1/1) and hexa-µ-acetato-(µ-N,2-dioxodo-benzene-1-carboximidato)fluorido-µ3-oxido-tri-pyridine-tetra-iron(III)-pyridine-water (1/1/0.24).

The title compounds, [Fe4(C2H3O2)6(C7H4O3)FO(C5H5N)3]·C5H5N·0.24H2O (1-F) and [Fe4(C2H3O2)6(C7H4O3)ClO(C5H5N)3]·H2O (1-Cl) were synthesized using a self-assembly reaction in methanol and pyridine with stoichiometric addition of salicyl-hydroxamic acid (H3shi), acetic acid (HOAc), and the appropriate ferric halide salt. The compounds crystallize as solvates, where 1-F has one pyridine mol-ecule that is disordered about a twofold axis and one water mol-ecule with an occupancy of 0.24 (2); and 1-Cl has one water mol-ecule that is disordered over two sites with occupancies of 0.71 (1) and 0.29 (1). The space groups for each analog differ as 1-F crystallizes in Fdd2 while 1-Cl crystallizes in P21. The difference in packing is due to changes in the inter-molecular inter-actions involving the different halides. The two mol-ecules are mostly isostructural, differing only by the torsion of the pyrine ligands and slight orientation changes in the acetate ligands. All of the iron(III) ions are in six-coordinate octa-hedral ligand field geometries but each one exhibits a unique coordination environment with various numbers of O (four to six) and N (nought to two) atom donors. Bond-valence sums confirm each iron is trivalent. The hydroximate ligand is bound to three iron(III) ions using a fused chelate motif similar to those in metallacrown compounds.

Versatile Para-Substituted Pyridine Lanthanide Coordination Complexes Allow Late Stage Tailoring of Complex Function.

A series of cationic and neutral p-Br and p-NO2 pyridine substituted Eu(III) and Gd(III) coordination complexes serve as versatile synthetic intermediates. Nucleophilic aromatic substitution occurs readily at the para position under mild conditions, allowing C-N and C-C bond forming reactions to take place, permitting the introduction of azide, amino and alkynyl substituents. For Eu(III) complexes, this approach allows late stage tuning of absorption and emission spectral properties, exemplified by the lowering of the energy of an LMCT transition accompanied by a reduction in the Eu-Npy bond length. Additionally, these complexes provide direct access to the corresponding Eu(II) analogues. With the Gd(III) series, the nature of the p-substituent does not significantly change the EPR properties (linewidth, relaxation times), as required for their development as EPR spin probes that can be readily conjugated to biomolecules under mild conditions.

Kinematics of a Novel Canine Cervical Fusion System.

OBJECTIVE: The aim of this study was to determine the biomechanical behaviour of a novel distraction-fusion system, consisting of an intervertebral distraction screw, pedicle locking screws and connecting rods, in the canine caudal cervical spine. STUDY DESIGN: Biomechanical study in cadaveric canine cervicothoracic (C3-T3) spines (n = 6). Cadaveric spines were harvested, stripped of musculature, mounted on a four-point bending jig, and tested using non-destructive four-point bending loads in extension (0-100 N), flexion (0-60 N) and lateral bending (0-40 N). Angular displacement was recorded from reflective optical trackers rigidly secured to C5, C6 and C7. Data for primary and coupled motions were collected from intact spines and following surgical stabilization (after ventral annulotomy and nucleotomy) with the new implant system. RESULTS: As compared with the intact spine, instrumentation significantly reduced motion at the operated level (C5-C6) with a concomitant non-significant increase at the adjacent level (C6-C7). CONCLUSION: The combination of a locking pedicle screw-rod system and intervertebral spacer provides an alternative solution for surgical distraction-stabilization in the canine caudal cervical spine and supports the feasibility of using this new implant system in the management of disc-associated cervical spondylomyelopathy in dogs. The increase in motion at C6-C7 may suggest the potential for adjacent level effects and clinical trials should be designed to address this.