Interconversion of the oxidation states of uranium enables separations and reactivity schemes involving this element and contributes to technologies for recycling of spent nuclear fuels. The redox behaviors of uranium species impact these processes, but use of electrochemical methods to drive reactions of molecular uranium complexes and to obtain molecular insights into the outcomes of electrode-driven reactions has received far less attention than it deserves. Here, we show that electro-reduction of the uranyl ion (UO2 2+) can be used to promote stepwise functionalization of the typically unreactive oxo groups with exogenous triphenylborane (BPh3) serving as a moderate electrophile, avoiding the conventional requirement for a chemical reductant. Parallel electroanalytical, spectrochemical, and chemical reactivity studies, supported by spectroscopic findings and structural data from X-ray diffraction analysis on key reduced and borylated products, demonstrate that our electrochemical approach largely avoids undesired cross reactions and disproportionation pathways; these usually impact the multicomponent systems needed for uranyl functionalization chemistry. Joint computational studies have been used to map the changes associated with U-O activation and to quantify the free energy differences related to key reactions. Taken together, the results suggest that electrochemical methods can be used for selective interconversion of molecular actinide species, reminiscent of methods commonly employed in transition metal redox catalysis.

Addition-type polynorbornenes have shown tremendous promise for a variety of applications; however, the direct polymerization of polar functionalized monomers is often challenging when using transition metal-based catalysts. This result is often ascribed to the oxophilic nature of many early transition metal species. Strategies to overcome this issue include the use of late transition metal catalysts, such as those containing Ni and Pd active sites, which generally exhibit greater monomer functional group tolerance. However, discrepancies in molecular weight and yield are still often encountered for the vinyl addition polymerization of polar vs nonpolar functionalized norbornene monomers. While researchers have studied these effects for Pd-based complexes, analogous studies using neutral, single-site nickel-based catalysts are absent from the literature. Herein, we show that polar functionalized norbornenes and a variety of polar additives readily coordinate LnNi(C6F5)2 type vinyl-addition polymerization catalysts and affect their polymerization behavior. These results suggest that simple trends in polynorbornene molecular weight are observed as a function of coordinating ligand (Ln) strength for the polymerization of nonpolar substituted norbornenes when using O-donor ligands of moderate coordination ability but do not fully explain why the polymerization of polar functionalized norbornenes routinely produce low molecular weight polymers in poor yields.

Kinetic studies on the intramolecular hydroamination of protected variants of 2,2-diphenylpent-4-en-1-amine were carried out under a variety of conditions with cationic gold catalysts supported by phosphine ligands. The impact of ligand on gold, protecting group on nitrogen, and solvent and additive on reaction rates was determined. The most effective reactions utilized more Lewis basic ureas, and more electron-withdrawing phosphines. A DCM/alcohol cooperative effect was quantified, and a continuum of isotope effects was measured with low KIE’s in the absence of deuterated alcoholic solvent, increasing to large solvent KIE’s when comparing reactions in pure MeOH to those in pure MeOH-d4. The effects are interpreted both within the context of a classic gold π-activation/protodeauration mechanism and a general acid-catalyzed mechanism without intermediate gold alkyls.

Both cyclic "crown" and acyclic "tiara" polyethers have been recognized as useful for the binding of metal cations and enabling the assembly of multimetallic complexes. However, the properties of heterobimetallic complexes built upon acyclic polyethers have received less attention than they deserve. Here, the synthesis and characterization of a family of eight redox-active heterobimetallic complexes that pair a nickel center with secondary redox-inactive cations (K+, Na+, Li+, Sr2+, Ca2+, Zn2+, La3+, and Lu3+) bound in acyclic polyether "tiara" moieties are reported. Structural studies with X-ray diffraction analysis were carried out on the monometallic nickel precursor complex to the heterobimetallics and the adducts with K+, Li+, Sr2+, Zn2+, and Lu3+; the results confirm the binding of secondary cations in the tiara site and demonstrate that the tiara moiety is more conformationally flexible than the analogous 18-crown-6-like moiety of a closely related macrocyclic "crown" ligand. Spectroscopic and electrochemical studies show, however, that the stability and cation-driven tunability of the tiara-based heterobimetallic species are quite similar to those previously measured for crown-based species. Consequently, the tiara motif appears to be at least as equally useful for constructing tunable multimetallic species as the more commonly encountered crown motif; a comprehensive set of titration data collected in an acetonitrile solution support this conclusion as well. Because the use of acyclic tiaras avoids the need for tedious and/or time-intensive syntheses of macrocyclic structures, these findings suggest that tiara motifs could be broadly advantageous in the design of ligands to support multimetallic chemistry.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Platinum-acridine anticancer agents (PAs) containingacyclic(1 and 3) and heterocyclic (R)-3-aminopiperidine (2) and 2-iminopyrrolidine (4) based linker moieties were studied. Similar to 1, rigidified 2 shows a strong positive correlation betweenpotency and SLC47A1 (multidrug and toxin extrusionprotein 1, MATE1) gene expression levels across the NCI-60 panel ofcancer cell lines. All derivatives show nanomolar activity in HepG2(liver), NCI-H460 (lung), and MDA-MB-436 (breast), which express highlevels of SLC47A1 (Cancer Cell Line Encyclopedia,CCLE). The PAs are up to 350-fold more potent than cisplatin. In aMATE1 inhibition assay, a significant reduction in activity is observedin the three cancer cell lines (4000-fold lower for HepG2). Moleculardocking experiments provide insight into the compatibility of thestructurally diverse set of PAs with MATE1-mediated transport. MATE1is a predictive marker and actionable target that sensitizes cancercells regardless of the tissue of origin to PAs.

A synthetic platform has been developed that provides access to platinum(IV) prodrugs of highly cytotoxic platinum-acridine anticancer agents and allows them to be incorporated into conjugation-ready prodrug-payloads (PPLs). The PPLs can be conveniently assembled in highly efficient microscale reactions utilizing strain-promoted azide-alkyne cycloaddition chemistry. Model reactions were performed to study the stability of the PPLs in buffers and media and to assess their compatibility with cysteine-maleimide Michael addition chemistry. Amide coupling was a successful strategy to generate a conjugate containing integrin-targeted cyclo[RGDfK] peptide. Reactions with ascorbate were performed to mimic the reductive activation of the PPLs and the latter conjugate, and a cyanine (Cy5) fluorophore-labeled PPL was used to probe the reduction of platinum(IV) in cancer cells by confocal microscopy. The PPL concept introduced here should be evaluated for treating solid tumors with PAs using cancer-targeting vehicles, such as antibody-drug conjugates.

An efficient and novel approach to accessing 3-selenylquinolines from diaryl diselenides and acyclic, selenium-free substrates is described. Preliminary mechanistic studies indicate that the combination of CuCl2 and air affords an appropriate environment for producing arylselenyl radicals that initiate the cascade cyclization of N-(2-alkynyl)anilines, forming key Se-C and C-C bonds in a single step. Using this chemistry, a wide variety of 3-selenylquinolines were produced in moderate to excellent yield under mild conditions, highlighting the versatility and usefulness of this new method.

Amide derivatives of xanthene dyes such as rhodamine B are useful in a variety of sensing applications due to their colorimetric responses to stimuli such as acidity changes and UV light. The optical properties of these molecules can be influenced by intermolecular associations into dimeric structures, but the exact impact can be hard to predict. We have designed a covalently linked intramolecular dimer of the dye rhodamine B utilizing p-phenylene diamine to link the two dyes via amide bonds. The doubly closed spirolactam version of this dimer, RSL2, is isolated as a colorless solid. Under acidic conditions or UV exposure, RSL2 solutions develop a pink color that is expected for the ring-opened form of the molecule. However, NMR and single crystal diffraction data show that the equilibrium still prefers the closed dimer state. Interestingly, the emission profile of RSL2 shows solvatochromic blue fluorescence. Control studies of model compounds with similar structural motifs do not display similar blue fluorescence, indicating that this optical behavior is unique to the dimeric form. This behavior may lend itself to applications of such xanthene dimers to more sophisticated sensors beyond those with traditional binary on/off fluorescence profiles.

Hybrid organic-inorganic metal-halide perovskites have emerged as versatile materials for enabling low-cost, mechanically flexible optoelectronic applications. The progress has been commendable; however, technological breakthroughs have outgrown the basic understanding of processes occurring in bulk and at device interfaces. Here, we investigated the photocurrent at perovskite/organic semiconductor interfaces in relation to the microstructure of electronically active layers. We found that the photocurrent response is significantly enhanced in the bilayer structure as a result of a more efficient dissociation of the photogenerated excitons and trions in the perovskite layer. The increase in the grain size within the organic semiconductor layer results in reduced trapping and further enhances the photocurrent by extending the photocarriers' lifetime. The photodetector responsivity and detectivity have improved by 1 order of magnitude in the optimized samples, reaching values of 6.1 ± 1.1 A W-1, and 1.5 × 1011 ± 4.7 × 1010 Jones, respectively, and the current-voltage hysteresis has been eliminated. Our results highlight the importance of fine-tuning film microstructure in reducing the loss processes in thin-film optoelectronics based on metal-halide semiconductors and provide a powerful interfacial design method to consistently achieve high-performance photodetectors.

A structure-activity relationship study was performed for a set of rigidified platinum-acridine anticancer agents containing linkers derived from chiral pyrrolidine and piperidine scaffolds. Screening a library of microscale reactions and selected resynthesized compounds in non-small-cell lung cancer (NSCLC) cells showed that cytotoxicities varied by more than three orders of magnitude. A potent hit compound was discovered containing a (R)-N-(piperidin-3-yl) linker (P2-6R), which killed NCI-H460 and A549 lung cancer cells 100 times more effectively than the S enantiomer (P2-6S). P2-6R accumulated in A549 cells significantly faster and produced 50-fold higher DNA adduct levels than P2-6S. Ligand similarity analysis suggests that only module 6R may be compatible with strainless monofunctional intercalative binding. NCI-60 screening and COMPARE analysis highlights the spectrum of activity and potential utility of P2-6R for treating NSCLC and other solid tumors.

Over the last three decades, the chemistry of zirconium has facilitated antibody development and the clinical management of disease in the precision medicine era. Scientists have harnessed its reactivity, coordination chemistry, and nuclear chemistry to develop antibody-based radiopharmaceuticals incorporating zirconium-89 (89Zr: t1/2 = 78.4 h, β+: 22.8%, Eβ+max = 901 keV; EC: 77%, Eγ = 909 keV) to improve disease detection, identify patients for individualized therapeutic interventions. and monitor their response to those interventions. However, release of the 89Zr4+ ion from the radiopharmaceutical remains a concern, since it may confound the interpretation of clinical imaging data, negatively affect dosimetric calculations, and hinder treatment planning. In this report, we relate our novel observations involving the use of polyazamacrocycles as zirconium-89 chelators. We describe the synthesis and complete characterization of zirconium 2,2',2″,2‴-(1,4,7,10-tetraazacyclotridecane-1,4,7,10-tetrayl)tetraacetic acid (Zr-TRITA), zirconium 3,6,9,15-Tetraazabicyclo[9.3.1] pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (Zr-PCTA), and zirconium 2,2',2″-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid (Zr-NOTA). In addition, we elucidate the solid-state structure of each complex using single-crystal X-ray diffraction analysis. Finally, we found that [89Zr]Zr-PCTA and [89Zr]Zr-NOTA demonstrate excellent stability in vitro and in vivo and provide a rationale for these observations. These innovative findings have the potential to guide the development of safer and more robust immuno-PET agents to improve precision medicine applications.

This paper describes the synthesis and characterization of RP­(o-biphenyl)2 phosphine ligands (where R = PhO, Ph, and t-Bu), corresponding gold­(I) chloride precatalysts, gold­(I) triflate catalysts, and gold­(I) π-complexes. All ligands and gold chlorides and three π-complexes were characterized in the solid state. The most significant differences between complexes in the solid state were varying P–Au bond lengths, a consistent reflection of the different electronic character of each phosphine. NMR spectroscopic data on enol ether π-complexes is consistent with increasing cationic character in the alkene fragment, from R = t-Bu to R = Ph and OPh. The intermolecular alkene exchange process for [LAu­(methoxypropene)]­SbF6 (L = PhO­(o-biphenyl)2P) is faster than that of the analogous complex with t-Bu2(o-biphenyl)­P, presumably due to the higher electrophilicity of the former complex. Examination of a series of vinyl silane π-complexes with triaryl phosphine ligands reveals increasing stability and ease of preparation (Ph3P < Ph2P­(o-biphenyl) < PhP­(o-biphenyl)2). These results reveal that incorporation of a second biphenyl substituent into ligand architectures allows preparation of a series of gold π-complexes with increased stability over a range of phosphine donicity.

A new layered gallium phosphonate-oxalate hybrid material, [C2H10N2]0.5[Ga3(PO3CH3)4(C2O4)].H2O, denoted as MOP-1, was synthesized under mild hydrothermal conditions (150 °C) in the presence of ethylenediammonium ion (H2en)2+ as structure-directing agent. The compound was structurally characterized by single-crystal X-ray diffraction (SCXRD), Fourier transformed infra-red spectroscopy (FTIR), and thermogravimetric analysis (TGA). Its structure consists of gallium phosphonate double layers formed of GaO6 octahedra, GaO4 tetrahedra, and PO3CH3 groups sharing corners. The double layers are cross-linked by oxalate ligands to form a three-dimensional framework with intersecting channels where the ammonium ions and water molecules are located. The bridging oxalate ligand acts as a bidentate ligand to each Ga in octahedral coordination environment. Crystal data are as follows: Monoclinic P21/n (14), a = 8.7530(5) Å; b = 16.3427(8) Å; c = 14.7522(8) Å; β = 93.284(1)°, V = 2106.8(2) Å3 and Z = 4.

Current treatment options for bacterial infections are dependent on antibiotics that inhibit microbial growth and viability. These approaches result in the evolution of drug-resistant strains of bacteria. An anti-infective strategy that is less likely to lead to the development of resistance is the disruption of quorum sensing mechanisms, which are involved in promoting virulence. The goal of this study was to identify fungal metabolites effective as quorum sensing inhibitors. Three new prenylated diresorcinols (1-3), along with two known compounds, (4 R) -regiolone and decarboxycitrinone, were isolated from a freshwater fungus (Helotiales sp.) from North Carolina. Their structures were assigned on the basis of HRESIMS and NMR experiments. The structure of compound 1 was confirmed via X-ray diffraction analysis, and its absolute configuration was established by TDDFT-ECD and optical rotation calculations. Compounds 1-3 suppressed quorum sensing in a clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA), with IC50 values ranging from 0.3 to 12.5 μM. These compounds represent potential leads in the development of antivirulence therapeutics.

Three new derivatives of a platinum-acridine hybrid anticancer agent were synthesized using nitrile-amine coupling (amidination) chemistry. In the new structures, the nonleaving group propane-1,3-diamine (pn) of a previously optimized analogue (hybrid 1) was replaced with 2,2-dimethylpropane-1,3-diamine (Me(2)pn, hybrid 2), (1R,2R)-1,2-diaminocyclohexane (R,R-dach, hybrid 3), or (1S,2S)-1,2-diaminocyclohexane (S,S-dach, hybrid 4). The cytotoxicity of the four compounds was determined in two non-small cell lung cancer (NSCLC) cell lines, NCI-H460 and A549. The IC50 values extracted from cell proliferation assays span a range of two orders of magnitude, with the highest activity established for compound 1 in NCI-H460 (8 nM) and the lowest for compound 4 in A549 (825 nM). Partitioning coefficients (log D, based on compound distribution in 1-octanol/saline) and levels of cellular accumulation (by inductively coupled plasma mass spectrometry, ICP-MS) were determined for the hybrids. The results suggest that efficient cellular uptake by an active transport mechanism, which depends on the nature of the nonleaving group, is a modulator of chemosensitivity and a prerequisite for the high nanomolar cytotoxicity observed for the most active platinum-acridines.

252 Introduction: The development of bifunctional chelators (BFCs) that can stably chelate zirconium-89 (89Zr) while being conjugated to targeting molecules is an area of active research (1). A recent publication described the extraordinary stability of the radiolabeled tetraazamacrocycle, 89Zr-DOTA in vivo (2). This work extends this research and examines the influence of macrocycle structure on the stability of these radiometal complexes. Methods: The non-radioactive Zr-tetraazamacrocycle complexes, Zr-NOTA, Zr-PCTA and Zr-TRITA were prepared using standard procedures, and the molecular structure of each complex was elucidated using single crystal x-ray diffraction analysis. The radioactive analogs were prepared using 89ZrCl4. In vitro, the radiometal complexes were challenged with exogenous chelating ligands, biologically relevant metal ions and human serum. Biodistribution and small animal PET studies were conducted in normal mice to examine the in vivo behavior of each radiometal complex. Results: Single crystal analysis revealed each Zr-complex to be octa-coordinate. Radiochemical studies revealed 89Zr-PCTA and 89Zr-NOTA to be extraordinarily inert to exogenous ligand, metal and serum challenge in vitro. Furthermore, biodistribution studies revealed rapid systemic clearance and low tissue retention of radioactivity. For example, mice injected with 89Zr-PCTA or 89Zr-NOTA retained less radioactivity in their kidney tissue than did mice receiving 89Zr-DFO (89Zr-PCTA vs. 89Zr-NOTAvs. 89Zr-DFO; mean %ID/g ± SD; [one-way ANOVA value, p value]: kidney (72 h): 0.15 ± 0.01 vs. 0.30 ± 0.023 vs. 0.69 ± 0.098; [F(3, 136), p