Automated radiolabeling and handling of 177 Lu- and 225 Ac-PSMA-617 using a robotic pipettor.

While automated modules for F-18 and C-11 radiosyntheses are standardized with features such as multiple reactors, vacuum connection and semi-preparative HPLC, labeling and processing of compounds with radiometals such as Zr-89, Lu-177 and Ac-225 often do not require complex manipulations and are frequently performed manually by a radiochemist. These procedures typically involve transferring solutions to and from vials using pipettes followed by heating of the reaction mixture, and do not require all the features found in most commercial automated synthesis units marketed as F-18 or C-11 modules. Here we present an efficient automated method for performing radiosyntheses involving radiometals by adapting a commercially available robotic pipettor originally developed for high-throughput processing of biological samples. While a robotic pipettor is less costly than a radiosynthesis module, it holds many similar advantages over manual radiosynthesis such as minimization of operator error, lower operator exposure rates, and abbreviated synthesis times, among others. To demonstrate the feasibility of using the OpenTrons OT-2 robotic pipettor to perform automated radiosyntheses, we radiolabeled and formulated 177 Lu-PSMA-617 and 225 Ac-PSMA-617 on the system. The OT-2 was then used to help streamline the quality control process for both products, further minimizing manual handling by and exposure to the radiochemist.

Preclinical Development of PNT6555, a Boronic Acid-Based, Fibroblast Activation Protein-α (FAP)-Targeted Radiotheranostic for Imaging and Treatment of FAP-Positive Tumors.

The overexpression of fibroblast activation protein-α (FAP) in solid cancers relative to levels in normal tissues has led to its recognition as a target for delivering agents directly to tumors. Radiolabeled quinoline-based FAP ligands have established clinical feasibility for tumor imaging, but their therapeutic potential is limited due to suboptimal tumor retention, which has prompted the search for alternative pharmacophores. One such pharmacophore is the boronic acid derivative N-(pyridine-4-carbonyl)-d-Ala-boroPro, a potent and selective FAP inhibitor (FAPI). In this study, the diagnostic and therapeutic (theranostic) potential of N-(pyridine-4-carbonyl)-d-Ala-boroPro-based metal-chelating DOTA-FAPIs was evaluated. Methods: Three DOTA-FAPIs, PNT6555, PNT6952, and PNT6522, were synthesized and characterized with respect to potency and selectivity toward soluble and cell membrane FAP; cellular uptake of the Lu-chelated analogs; biodistribution and pharmacokinetics in mice xenografted with human embryonic kidney cell-derived tumors expressing mouse FAP; the diagnostic potential of 68Ga-chelated DOTA-FAPIs by direct organ assay and small-animal PET; the antitumor activity of 177Lu-, 225Ac-, or 161Tb-chelated analogs using human embryonic kidney cell-derived tumors expressing mouse FAP; and the tumor-selective delivery of 177Lu-chelated DOTA-FAPIs via direct organ assay and SPECT. Results: DOTA-FAPIs and their natGa and natLu chelates exhibited potent inhibition of human and mouse sources of FAP and greatly reduced activity toward closely related prolyl endopeptidase and dipeptidyl peptidase 4. 68Ga-PNT6555 and 68Ga-PNT6952 showed rapid renal clearance and continuous accumulation in tumors, resulting in tumor-selective exposure at 60 min after administration. 177Lu-PNT6555 was distinguished from 177Lu-PNT6952 and 177Lu-PNT6522 by significantly higher tumor accumulation over 168 h. In therapeutic studies, all 3 177Lu-DOTA-FAPIs exhibited significant antitumor activity at well-tolerated doses, with 177Lu-PNT6555 producing the greatest tumor growth delay and animal survival. 225Ac-PNT6555 and 161Tb-PNT6555 were similarly efficacious, producing 80% and 100% survival at optimal doses, respectively. Conclusion: PNT6555 has potential for clinical translation as a theranostic agent in FAP-positive cancer.

Radiosynthesis and Early Evaluation of a Positron Emission Tomography Imaging Probe [18F]AGAL Targeting Alpha-Galactosidase A Enzyme for Fabry Disease.

Success of gene therapy relies on the durable expression and activity of transgene in target tissues. In vivo molecular imaging approaches using positron emission tomography (PET) can non-invasively measure magnitude, location, and durability of transgene expression via direct transgene or indirect reporter gene imaging in target tissues, providing the most proximal PK/PD biomarker for gene therapy trials. Herein, we report the radiosynthesis of a novel PET tracer [18F]AGAL, targeting alpha galactosidase A (α-GAL), a lysosomal enzyme deficient in Fabry disease, and evaluation of its selectivity, specificity, and pharmacokinetic properties in vitro. [18F]AGAL was synthesized via a Cu-catalyzed click reaction between fluorinated pentyne and an aziridine-based galactopyranose precursor with a high yield of 110 mCi, high radiochemical purity of >97% and molar activity of 6 Ci/µmol. The fluorinated AGAL probe showed high α-GAL affinity with IC50 of 30 nM, high pharmacological selectivity (≥50% inhibition on >160 proteins), and suitable pharmacokinetic properties (moderate to low clearance and stability in plasma across species). In vivo [18F]AGAL PET imaging in mice showed high uptake in peripheral organs with rapid renal clearance. These promising results encourage further development of this PET tracer for in vivo imaging of α-GAL expression in target tissues affected by Fabry disease.

Content Analysis of Feedback Journals for New Nurses From Preceptor Nurses Using Text Network Analysis.

This study aimed to identify keywords, core topic areas, and subthemes by analyzing feedback journals written by preceptor nurses to new nurses during the preceptorship period and to derive implications through word clustering. A total of 143 preceptor nurses' feedback journals for new nurses from March 2020 to January 2021 were converted into a database using Microsoft Office Excel. Text network analysis was performed using the NetMiner 4.4.3 program. After data preprocessing, simple frequency, degree centrality, closeness centrality, betweenness centrality, and community modularity were analyzed. In the feedback journals, the most central words were "study," "medication," "practice," "nursing," "method," "need," and "effort," whereas frustration, "new nurses" had low centrality. Five subthemes were derived: (1) learning necessity to strengthen new nurses' competency, (2) independence of new nurses, (3) emphasis on accuracy in nursing skills, (4) difficulties in understanding the nursing tasks expected of new nurses, and (5) basic competency of new nurses. The results of this study highlighted the experiences of new nurses and allowed for an assessment of journal feedback content provided by preceptor nurses. As such, the study provides basic data to develop a standardized education and competency empowerment program for preceptor nurses.

Radiometallation and photo-triggered release of ready-to-inject radiopharmaceuticals from the solid phase.

The efficient, large-scale synthesis of radiometallated radiopharmaceuticals represents an emerging clinical need which, to date, is inherently limited by time consuming, sequential procedures to conduct isotope separation, radiochemical labeling and purification prior to formulation for injection into the patient. In this work, we demonstrate that a solid-phase based, concerted separation and radiosynthesis strategy followed by photochemical release of radiotracer in biocompatible solvents can be employed to prepare ready-to-inject, clinical grade radiopharmaceuticals. Optimization of resin base, resin loading, and radiochemical labeling capacity are demonstrated with 67Ga and 64Cu radioisotopes using a short model peptide sequence and further validated using two peptide-based radiopharmaceuticals with clinical relevance, targeting the gastrin-releasing peptide and the prostate specific membrane antigen. We also demonstrate that the solid-phase approach enables separation of non-radioactive carrier ions Zn2+ and Ni2+ present at 105-fold excess over 67Ga and 64Cu by taking advantage of the superior Ga3+ and Cu2+ binding affinity of the solid-phase appended, chelator-functionalized peptide. Finally, a proof of concept radiolabeling and subsequent preclinical PET-CT study with the clinically employed positron emitter 68Ga successfully exemplifies that Solid Phase Radiometallation Photorelease (SPRP) allows the streamlined preparation of radiometallated radiopharmaceuticals by concerted, selective radiometal ion capture, radiolabeling and photorelease.

Landscape of prostate-specific membrane antigen heterogeneity and regulation in AR-positive and AR-negative metastatic prostate cancer.

Tumor expression of prostate-specific membrane antigen (PSMA) is lost in 15-20% of men with castration-resistant prostate cancer (CRPC), yet the underlying mechanisms remain poorly defined. In androgen receptor (AR)-positive CRPC, we observed lower PSMA expression in liver lesions versus other sites, suggesting a role of the microenvironment in modulating PSMA. PSMA suppression was associated with promoter histone 3 lysine 27 methylation and higher levels of neutral amino acid transporters, correlating with 18F-fluciclovine uptake on positron emission tomography imaging. While PSMA is regulated by AR, we identified a subset of AR-negative CRPC with high PSMA. HOXB13 and AR co-occupancy at the PSMA enhancer and knockout models point to HOXB13 as an upstream regulator of PSMA in AR-positive and AR-negative prostate cancer. These data demonstrate how PSMA expression is differentially regulated across metastatic lesions and in the context of the AR, which may inform selection for PSMA-targeted therapies and development of complementary biomarkers.

Capturing New Nurses' Experiences and Supporting Critical Thinking: Text Network Analysis of Critical Reflective Journals.

This study analyzed the contents of critical reflective journals written by new nurses during their orientations using a text network. This study aimed to find ways to reduce turnover and improve clinical field adaptability among new nurses. The authors analyzed the content of reflective journals written by 143 new nurses from March 2020 to January 2021. Text network analysis was performed using the NetMiner 4.4.3 program. After data preprocessing, frequency of occurrence, degree centrality, closeness centrality, betweenness centrality, and eigenvector community were analyzed. In total, 453 words were extracted and refined, and words with high simple frequency and centrality were "incompetence," "preparation," "explanation," "injection," "time," "examination," and "first try." "Medication" had the highest frequency of occurrence, and "incompetence" was the most important keyword in the centrality analysis. In addition, component analysis and eigenvector community analysis revealed three sub-theme groups: (1) basic nursing skills required for new nurses, (2) insufficient competency, and (3) explanation of nursing work. Significantly, this study is the first to use the text network method to analyze the subjective experiences of the critical reflective journals of new nurses. In conclusion, changes are needed to improve the education system for new nurses and promote efficient sharing of nursing tasks.

Effect of a hybrid team-based advanced cardiopulmonary life support simulation program for clinical nurses.

BACKGROUND: During in-hospital cardiac arrest events, clinical nurses are often the first responders; therefore, nurses require sufficient advanced cardiac life support (ACLS) competency. This study aimed to verify the effects of a hybrid team-based ACLS simulation (HTAS) program (developed in this study) on nurses' ACLS performance, specifically ACLS knowledge, cardiopulmonary resuscitation (CPR) self-efficacy, and CPR-related stress. METHODS: The developed HTAS comprised four lecture videos, one team-based skills training video, and a team-based ACLS simulation. A quasi-experimental pretest-posttest design with a comparison group (CG) was used to evaluate the effectiveness of the HTAS. Of the 226 general ward nurses with more than 6 months of clinical experience, 117 were allocated to the intervention group (IG), which attended the HTAS, and 109 to the CG, which attended only basic ACLS training. RESULTS: The IG's ACLS performance significantly improved (t = 50.8, p < 0.001) after the training. Relative to the respective pretest conditions, posttest ACLS knowledge (t = 6.92, p < 0.001) and CPR self-efficacy (t = 6.97, p < 0.001) of the IG also significantly increased. However, when the mean difference values were compared, there was no significant difference between the two groups with respect to ACLS knowledge (t = 1.52, p = 0.130), CPR self-efficacy (t = -0.42, p = 0.673), and CPR stress (t = -0.88, p = 0.378). CONCLUSION: The HTAS for ward nurses was effective at enhancing the nurses' ACLS performance. It is necessary to develop effective training methods for team-based ACLS and verify the sustained effects of such training.

Development and Preliminary Evaluation of the Effects of a Preceptor Reflective Practice Program: A Mixed-Method Research.

Studies on methods to share nursing and learning experiences with preceptors are lacking. This study was conducted to determine the preliminary effects of developing and applying a reflective practice program for preceptor nurses who experience stressful situations to convert negative emotions into positive ones. This study was conducted over 12 weeks from March to May 2022 on 47 participant nurses in South Korea. Preceptor Reflective Practice Program (PRPP) was conducted in parallel with writing a reflective journal and a reflective practice workshop. Data collection was integrated through quantitative and qualitative approaches. Quantitative data were collected through questionnaires on stress coping, the burden of preceptors, social support, and emotional intelligence, and analyzed by SPSS WIN 26.0 program. The questionnaire data were analyzed after the preceptor nurses had written a reflective journal. Stress coping, social support, and emotional intelligence significantly increased in preceptor nurses after participating in the PRPP. This study found that the PRPP helped nurses improve their emotional intelligence through reflective practice and convert stress into a more positive direction. Therefore, at the organizational and national levels, a reasonable compensation system to provide support workforce and to the work of preceptor nurses should be established.

Homologous Structural, Chemical, and Biological Behavior of Sc and Lu Complexes of the Picaga Bifunctional Chelator: Toward Development of Matched Theranostic Pairs for Radiopharmaceutical Applications.

The radioactive isotopes scandium-44/47 and lutetium-177 are gaining relevance for radioimaging and radiotherapy, resulting in a surge of studies on their coordination chemistry and subsequent applications. Although the trivalent ions of these elements are considered close homologues, dissimilar chemical behavior is observed when they are complexed by large ligand architectures due to discrepancies between Lu(III) and Sc(III) ions with respect to size, chemical hardness, and Lewis acidity. Here, we demonstrate that Lu and Sc complexes of 1,4-bis(methoxycarbonyl)-7-[(6-carboxypyridin-2-yl)methyl]-1,4,7-triazacyclononane (H3mpatcn) and its corresponding bioconjugate picaga-DUPA can be employed to promote analogous structural features and, subsequently, biological properties for coordination complexes of these ions. The close homology was evidenced using potentiometric methods, computational modeling, variable temperature mass spectrometry, and pair distribution function analysis of X-ray scattering data. Radiochemical labeling, in vitro stability, and biodistribution studies with Sc-47 and Lu-177 indicate that the 7-coordinate ligand environment of the bifunctional picaga ligand is compatible with biological applications and the future investigation of ß-emitting, picaga-chelated Sc and Lu isotopes for radiotherapy.

Is Less More? Influence of the Coordination Geometry of Copper(II) Picolinate Chelate Complexes on Metabolic Stability.

A growing number of copper(II) complexes have been identified as suitable candidates for biomedical applications. Here, we show that the biocompatibility and stability of copper(II) complexes can be tuned by directed ligand design and complex geometry. We demonstrate that azamacrocycle-based chelators that envelope copper(II) in a five-coordinate, distorted trigonal-bipyramidal structure are more chemically inert to redox-mediated structural changes than their six-coordinate, Jahn-Teller-distorted counterparts, as evidenced by electrochemical, crystallographic, electron paramagnetic resonance, and density functional theory studies. We further validated our hypothesis of enhanced inertness in vitro and in vivo by employing Cu-64 radiolabeling of bifunctional analogues appended to a prostate-specific membrane antigen targeting dipeptide. The corresponding Cu-64 complexes were tested for stability in vitro and in vivo, with the five-coordinate system demonstrating the greatest metabolic stability among the studied picolinate complex series.

Chelation with a twist: a bifunctional chelator to enable room temperature radiolabeling and targeted PET imaging with scandium-44.

Scandium-44 has emerged as an attractive, novel PET radioisotope with ideal emission properties and half-life (t 1/2 = 3.97 h, E mean ß+ = 632 keV) well matched to the pharmacokinetics of small molecules, peptides and small biologics. Conjugates of the current gold-standard chelator for 44Sc, 1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetraacetic acid (DOTA), require heating to achieve radiochemical complexation, limiting application of this isotope in conjunction with temperature-sensitive biologics. To establish Sc(iii) isotopes as broadly applicable tools for nuclear medicine, development of alternative bifunctional chelators is required. To address this need, we characterized the Sc(iii)-chelation properties of the small-cavity triaza-macrocycle-based, picolinate-functionalized chelator H3mpatcn. Spectroscopic and radiochemical studies establish the [Sc(mpatcn)] complex as kinetically inert and appropriate for biological applications. A proof-of-concept bifunctional conjugate targeting the prostate-specific membrane antigen (PSMA), picaga-DUPA, chelates 44Sc to form 44Sc(picaga)-DUPA at room temperature with an apparent molar activity of 60 MBq µmol-1 and formation of inert RRR-Λ and SSS-Δ-twist isomers. Sc(picaga)-DUPA exhibits a K i of 1.6 nM for PSMA, comparable to the 18F-based imaging probe DCFPyL (K i = 1.1 nM) currently in phase 3 clinical trials for imaging prostate cancer. Finally, we successfully employed 44Sc(picaga)-DUPA to image PSMA-expressing tumors in a preclinical mouse model, establishing the picaga bifunctional chelator as an optimal choice for the 44Sc PET nuclide.

Trivalent metal complex geometry of the substrate governs cathepsin B enzymatic cleavage rate.

The lysosomal protease cathepsin B recognizes defined, short peptide sequences, providing means for effective, targeted drug release. Here, we show that the introduction of a coordination complex adjacent to the cleavage sequence allows us to tune enzymatic cleavage rate by varying the complexed, trivalent metal ion.

Site-Specific 89Zr- and 111In-Radiolabeling and In Vivo Evaluation of Glycan-free Antibodies by Azide-Alkyne Cycloaddition with a Non-natural Amino Acid.

Antibody-drug conjugates (ADCs) are a class of targeted therapeutics consisting of a monoclonal antibody coupled to a cytotoxic payload. Various bioconjugation methods for producing site-specific ADCs have been reported recently, in efforts to improve immunoreactivity and pharmacokinetics and minimize batch variance-potential issues associated with first-generation ADCs prepared via stochastic peptide coupling of lysines or reduced cysteines. Recently, cell-free protein synthesis of antibodies incorporating para-azidomethyl phenylalanine (pAMF) at specific locations within the protein sequence has emerged as a means to generate antibody-drug conjugates with strictly defined drug-antibody-ratio, leading to ADCs with markedly improved stability, activity, and specificity. The incorporation of pAMF enables the conjugation of payloads functionalized for strain-promoted azide-alkyne cycloaddition. Here, we introduce two dibenzylcyclooctyne-functionalized bifunctional chelators that enable the incorporation of radioisotopes for positron emission tomography with 89Zr (t1/2 = 78.4 h, ß+ = 395 keV (22%), γ = 897 keV) or single photon emission computed tomography with 111In (t1/2 = 67.3 h, γ = 171 keV (91%), 245 keV (94%)) under physiologically compatible conditions. We show that the corresponding radiolabeled conjugates with site-specifically functionalized antibodies targeting HER2 are amenable to targeted molecular imaging of HER2+ expressing tumor xenografts in mice and exhibit a favorable biodistribution profile in comparison with conventional, glycosylated antibody conjugates generated by stochastic bioconjugation.

Theranostic Gallium Siderophore Ciprofloxacin Conjugate with Broad Spectrum Antibiotic Potency.

Pathogenic bacteria scavenge ferric iron from the host for survival and proliferation using small-molecular chelators, siderophores. Here, we introduce and assess the gallium(III) complex of ciprofloxacin-functionalized desferrichrome (D2) as a potential therapeutic for bacterial infection using an in vitro assay and radiochemical, tracer-based approach. Ga-D2 exhibits a minimum inhibitory concentration of 0.23 µM in Escherichia coli, in line with the parent fluoroquinolone antibiotic. Competitive and mutant strain assays show that Ga-D2 relies on FhuA-mediated transport for internalization. Ga-D2 is potent against Pseudomonas aeruginosa (3.8 µM), Staphylococcus aureus (0.94 µM), and Klebsiella pneumoniae (12.5 µM), while Fe-D2 is inactive in these strains. Radiochemical experiments with E. coli reveal that 67Ga-D2 is taken up more efficiently than 67Ga-citrate. In naive mice, 67Ga-D2 clears renally and is excreted 13% intact in the urine. These pharmacokinetic and bacterial growth inhibitory properties qualify Ga-D2 for future investigations as a diagnosis and treatment tool for infection.

Linear Desferrichrome-Linked Silicon-Rhodamine Antibody Conjugate Enables Targeted Multimodal Imaging of HER2 in Vitro and in Vivo.

We report the nuclear and optical in vitro and in vivo imaging of SKOV-3 cells by targeting HER2 with a bimodal trastuzumab conjugate. Previously, we have shown that desferrichrome derivatives provide a robust and versatile radiolabeling platform for the radioisotope zirconium-89. Here, we appended silicon-rhodamine functionalized linear desferrichrome to trastuzumab. This construct was radiolabeled and used to image cellular binding and antibody uptake in vitro and in vivo. The robust extinction coefficient of the SiR deep-red emissive fluorophore enables direct quantification of the number of appended chelators and fluorophore molecules per antibody. Subsequent radiolabeling of the multifunctional immunoconjugate with 89Zr was achieved with a 64 ± 9% radiochemical yield, while the reference immunoconjugate desferrioxamine (DFO)-trastuzumab exhibited a yield of 84 ± 9%. In vivo PET imaging (24, 48, 72, and 96 h post injection) and biodistribution experiments (96 h post injection) in HER2+ tumor bearing mice revealed no statistically significant difference of the two 89Zr-labeled conjugates at each time point evaluated. The bimodal conjugate permitted successful in vivo fluorescence imaging (96 h post injection) and subsequent fluorescence-guided, surgical resection of the tumor mass. This report details the first successful application of a fluorophore-functionalized desferrichrome derivative for targeted imaging, motivating further development and application of this scaffold as a multimodal imaging platform.

Cherenkov Radiation-Mediated In†Situ Excitation of Discrete Luminescent Lanthanide Complexes.

Lanthanide luminescence, while ideal for in vivo applications owing to sharp emission bands within the optical window, requires high-intensity, short-wavelength excitation of small organic "antenna" chromophores in the vicinity of the lanthanide complex to access excited f-orbital states through intersystem crossing. Herein, we explored Cherenkov radiation of the radioisotopes 18 F and 89 Zr as an in situ source of antenna excitation. The effective inter- and intramolecular excitation of the terbium(III) complexes of a macrocylic polyaminocarboxylate ligand (hydration number (q)=0, quantum yield (φ)=47 %) as well as its analogue functionalized to append an intramolecular Cherenkov excitation source (q=0.07, φ=63 %) was achieved. Using conventional small-animal fluorescence imaging equipment, we have determined a detection limit of 2.5 nmol of Tb(III) complex in presence of 10 µCi of 18 F or 89 Zr. Our system is the first demonstration of the optical imaging of discrete luminescent lanthanide complexes without external short-wave excitation.

Nuclear and Optical Bimodal Imaging Probes Using Sequential Assembly: A Perspective.

New, targeted imaging tracers enable improved diagnosis, staging, and planning of treatment of disease and represent an important step toward personalized medicine applications. The combination of radioisotopes for nuclear imaging with fluorophores for fluorescence imaging provides the possibility to noninvasively assess disease burden in a patient using positron emission tomography/single-photon emission computed tomography, followed by fluorescence imaging-assisted surgical intervention in close succession. Probes enabling imaging with both modalities pose a design, synthesis, and pharmacokinetics challenge. In this study, the authors strive to summarize recent efforts toward optimized, discrete, bimodal probes as well as a perspective on future directions of this burgeoning subfield of targeted imaging probe development.

Di(hydroperoxy)alkane Adducts of Phosphine Oxides: Safe, Solid, Stoichiometric, and Soluble Oxidizing Agents.

The di(hydroperoxy)alkane adducts of phosphine oxides 1-9, Ph3 PO⋅(HOO)2 CMe2 , Cy3 PO⋅(HOO)2 CMe2 , Ph3 PO⋅ (HOO)2 CMeEt, Cy3 PO⋅(HOO)2 CMeEt, Cy3 PO⋅(HOO)2 CEt2 , Cy3 PO⋅ (HOO)2 C(CH2 )5 , Cy3 PO⋅(HOO)2 CMePh, (Ph2 P(O)CH2 CH2 P(O)Ph2 )⋅ ((HOO)2 CEt2 )2 , and Ph2 P(O)CH2 P(O)Ph2 ⋅(HOO)2 CMe2 , respectively, are synthesized and fully characterized by 1 H, 13 C, and 31 P NMR, and IR spectroscopies. Single crystal X-ray structures are reported for 3-9. Different one-pot synthetic pathways, starting from R3 P, R3 PO, R3 PO⋅H2 O, and R3 PO⋅H2 O2 are explored and discussed and a mechanism for the formation of the di(hydroperoxy)alkane adducts of phosphine oxides is suggested. The longevity of the adducts is tested by monitoring the oxidation of Ph3 P with quantitative NMR. The solubilities of the adducts in organic solvents are presented, and their applicability as stoichiometric oxidizing agents for the selective oxidation of sulfides to sulfoxides is reported.

Hydrogen Peroxide and Di(hydroperoxy)propane Adducts of Phosphine Oxides as Stoichiometric and Soluble Oxidizing Agents.

Aqueous hydrogen peroxide is widely used as an oxidizing agent in industry and academia. Herein, the hydrogen peroxide adducts of phosphine oxides, [tBu3PO⋅H2O2]2 and [Ph3PO⋅H2O2]2⋅H2O2, are described. Additionally, the corresponding di(hydroperoxy)propane adducts R3PO⋅(HOO)2CMe2 (R=Cy, Ph) were synthesized and characterized. All adducts could be obtained as large single crystals suitable for structural characterization by X-ray crystallography and solid-state NMR spectroscopy. The di(hydroperoxy)propane adducts are soluble in organic solvents which enables oxidation reactions in one phase. As the adducts are solid and molecular, they can easily be applied stoichiometrically. No loss of oxidizing power occurs upon long-term storage of the single crystals at room temperature or the powders at -20 °C.