Photo- and Electrocatalytic Hydrogen Evolution by Heteroleptic Dirhodium(II,II) Complexes: Role of the Bridging and Diimine Ligands.

A series of heteroleptic Rh2(II,II) complexes, cis-[Rh2(µ-DPhF)2(µ-bncn)2]2+ (1; bncn = benzo[c]cinnoline), cis-[Rh2(µ-DPhF)(µ-OAc)(µ-bncn)2]2+ (2), and cis-[Rh2(µ-OAc)2(µ-bncn)2]2+ (3), is presented, and the excited state and redox properties of each complex was characterized for the photo- and electrocatalytic production of H2. The oxidation potentials shift anodically from 1 to 3, consistent with a highest occupied molecular orbital (HOMO) with significant metal-ligand mixing, Rh2(δ*)/DPhF(π/nb). In contrast, modest differences in the first two bncn-localized reversible reduction potentials were observed in 1 - 3. The lowest energy metal/ligand-to-ligand charge transfer (1ML-LCT) transition, Rh2(δ*)/DPhF(π/nb) → bncn(π*), shifts from 633 nm in 1 to 553 nm in 2, and the metal-to-ligand charge transfer (1MLCT) Rh2(π*) → bncn(π*) absorption in 3 appears at 462 nm in CH3CN. Although the 3ML-LCT excited state of 2 is shorter lived than that of 1, 2.7 ns as compared to 19 ns, respectively, photocatalytic hydrogen generation is observed for the former upon 595 nm irradiation in the presence of 0.1 M TsOH (p-tolylsulfonic acid) and 0.1 M BNAH (1-benzyl-1,4-dihydronicotinamide). The temperature dependence of the 3ML-LCT lifetimes of 1 and 2 shows the presence of a thermally accessible deactivating state. In addition, the singly reduced intermediate, [2]-, is photoactive and able to generate hydrogen in the presence of TsOH. Importantly, the electrocatalytic currents generated by equimolar concentrations of 1 - 3 in CH3CN are nearly identical, consistent with a mechanism of catalysis that is localized on the bncn ligand and does not require a Rh-H hydride intermediate. This finding can be used to develop earth-abundant first-row transition metal complexes for photo- and electrocatalytic H2 production.

Hydrogen atom abstraction as a synthetic route to a square planar CoII complex with a redox-active tetradentate PNNP ligand.

Redox-active ligands improve the reactivity of transition metal complexes by facilitating redox processes independent of the transition metal center. A tetradentate square planar (PNCH2CH2NP)CoII (1) complex was synthesized and the ethylene backbone was dehydrogenated through hydrogen atom abstraction to afford (PNCHCHNP)CoII (2), which now contains a redox-active ligand. The ligand backbone of 2 can be readily hydrogenated with H2 to regenerate 1. Reduction of 1 and 2 with KC8 in the presence of 18-crown-6 results in cobalt-based reductions to afford [(PNCH2CH2NP)CoI][K(18-crown-6)] (3) and [(PNCHCHNP)CoI][K(18-crown-6)] (4), respectively. Cyclic voltammetry revealed two reversible oxidation processes for 2, presumed to be ligand-based. Following treatment of 2 with one equivalent of FcPF6, the one-electron oxidation product {[(PNCHCHNP)CoII(THF)][PF6]}·THF (5) was obtained. Treating 5 with an additional equivalent of FcPF6 affords the two-electron oxidation product [(PNCHCHNP)CoII][PF6]2 (6). Addition of PMe3 to 5 produced [(PNCHCHNP)CoII(PMe3)][PF6] (7). A host of characterization methods including nuclear magnetic resonance (NMR) spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, cyclic voltammetry, magnetic susceptibility measurements using SQUID magnetometry, single-crystal X-ray diffraction, and density functional theory calculations were used to assign 5 and 6 as ligand-based oxidation products of 2.

Reductive alkyl-alkyl coupling from isolable nickel-alkyl complexes.

The selective cross-coupling of two alkyl electrophiles to construct complex molecules remains a challenge in organic synthesis1,2. Known reactions are optimized for specific electrophiles and are not amenable to interchangeably varying electrophilic substrates that are sourced from common alkyl building blocks, such as amines, carboxylic acids and halides3-5. These limitations restrict the types of alkyl substrate that can be modified and, ultimately, the chemical space that can be explored6. Here we report a general solution to these limitations that enables a combinatorial approach to alkyl-alkyl cross-coupling reactions. This methodology relies on the discovery of unusually persistent Ni(alkyl) complexes that can be formed directly by oxidative addition of alkyl halides, redox-active esters or pyridinium salts. The resulting alkyl complexes can be isolated or directly telescoped to couple with a second alkyl electrophile, which represent cross-selective reactions that were previously unknown. The utility of this synthetic capability is showcased in the rapid diversification of amino acids, natural products, pharmaceuticals and drug-like building blocks by various combinations of dehalogenative, decarboxylative or deaminative coupling. In addition to a robust scope, this work provides insights into the organometallic chemistry of synthetically relevant Ni(alkyl) complexes through crystallographic analysis, stereochemical probes and spectroscopic studies.

Epidemiology of Mpox Cases, and Tecovirimat and JYNNEOS Utilization, Alameda County, California, June-October 2022.

CONTEXT: The 2022 United States mpox outbreak disproportionately affected racial and ethnic minority gay, bisexual, and other men who have sex with men. PROGRAM: We utilized surveillance data and vaccination registries to determine whether populations most impacted by mpox in Alameda County received JYNNEOS vaccines and tecovirimat (TPOXX) during June 1-October 31, 2022. IMPLEMENTATION: Alameda County Public Health Department responded to the mpox epidemic through partnerships with local health care providers who serve communities disproportionately affected by mpox. EVALUATION: During June 1-October 31, 2022, a total of 242 mpox cases were identified in Alameda County. Mpox incidence rates per 100 000 were highest among Black/African American (35.7; 95% confidence interval [CI], 26.8-46.5) and Hispanic/Latinx (25.1; CI, 20.1-30.9) residents, compared to Asian (3.8; CI, 2.3-5.9) and White (10.5; CI, 7.7-13.9) residents. Most confirmed cases were identified as gay, lesbian, or same-gender-loving (134, 67.3%) and bisexual (31, 15.6%); 226 (93.8%) cases were male. Sixty-nine (28.5%) mpox patients received TPOXX. There were no statistically significant differences in demographic and clinical characteristics of mpox cases when compared by TPOXX receipt status. JYNNEOS vaccine was received by 8277 Alameda County residents. The largest proportion of vaccinees were White residents (40.2%). Administration rates per 100 000 men who have sex with men were lowest among Asian and Hispanic/Latinx individuals, at 8779 (CI, 8283-9296) and 14 953 (CI, 14 156-15 784), respectively. Black/African American and Hispanic/Latinx males had the lowest vaccination-to-case ratios at 16.7 and 14.8, respectively. DISCUSSION: Mpox disproportionately affected Black/African American and Hispanic/Latinx men who have sex with men in Alameda County. Strong partnerships with local health care providers ensured that persons with mpox received TPOXX treatment when indicated. However, higher JYNNEOS vaccine uptake in Black and Latinx communities needs improvement through ongoing and meaningful engagement with Black/African American and Hispanic/Latinx gay, bisexual, and transgender communities.

Molecular bowls for inclusion complexation of toxic anticancer drug methotrexate.

We describe the preparation and study of novel cavitands, molecular bowls 16+ and 26+, as good binders of the anticancer drug methotrexate (MTX). Molecular bowls are comprised of a curved tribenzotriquinacene (TBTQ) core conjugated to three macrocyclic pyridinium units at the top. The cavitands are easily accessible via two synthetic steps from hexabromo-tribenzotriquinacene in 25% yield. As amphiphilic molecules, bowls 16+ and 26+ self-associate in water by the nucleation-to-aggregation pathway (NMR). The bowls are preorganized, having a semi-rigid framework comprising a fixed bottom with a wobbling pyridinium rim (VT NMR and MD). Further studies, both experimental (NMR) and computational (DFT and MCMM), suggested that a folded MTX occupies the cavity of bowls wherein it forms π-π, C-H-π, and ion pairing intermolecular contacts but also undergoes desolvation to give stable binary complexes (µM) in water. Moreover, a computational protocol is introduced to identify docking pose(s) of MTX inside molecular bowls from NMR shielding data. Both molecular bowls have shown in vitro biocompatibility with liver and kidney cell lines (MTS assay). As bowl 26+ is the strongest binder of MTX reported to date, we envision it as an excellent candidate for further studies on the way toward developing an antidote capable of removing MTX from overdosed cancer patients.

Arginine Acts as both Co-solvent and Catalyst in Regioselective Eutectic-Mediated Dimerization of Levulinic Acid.

Invited for this issue's cover are Procter & Gamble's Corporate Analytical and Engineering Groups, along with the group of Professor Jovica Badjic and colleagues. The image, by Jennifer F. Neal, depicts the process of chemically upgrading the renewable, biomass-derived levulinic acid by simplying mixing it with l-arginine. The Research Article itself is available at 10.1002/cssc.202400503.

Two-Dimensional Cobalt(II) Benzoquinone Frameworks for Putative Kitaev Quantum Spin Liquid Candidates.

The realization and discovery of quantum spin liquid (QSL) candidate materials are crucial for exploring exotic quantum phenomena and applications associated with QSLs. Most existing metal-organic two-dimensional (2D) quantum spin liquid candidates have structures with spins arranged on the triangular or kagome lattices, whereas honeycomb-structured metal-organic compounds with QSL characteristics are rare. Here, we report the use of 2,5-dihydroxy-1,4-benzoquinone (X2dhbq, X = Cl, Br, H) as the linkers to construct cobalt(II) honeycomb lattices (NEt4)2[Co2(X2dhbq)3] as promising Kitaev-type QSL candidate materials. The high-spin d7 Co2+ has pseudospin-1/2 ground-state doublets, and benzoquinone-based linkers not only provide two separate superexchange pathways that create bond-dependent frustrated interactions but also allow for chemical tunability to mediate magnetic coupling. Our magnetization data show antiferromagnetic interactions between neighboring metal centers with Weiss constants from -5.1 to -8.5 K depending on the X functional group in X2dhbq linkers (X = Cl, Br, H). No magnetic transition or spin freezing could be observed down to 2 K. Low-temperature susceptibility (down to 0.3 K) and specific heat (down to 0.055 K) of (NEt4)2[Co2(H2dhbq)3] were further analyzed. Heat capacity measurements confirmed no long-range order down to 0.055 K, evidenced by the broad peak instead of the λ-like anomaly. Our results indicate that these 2D cobalt benzoquinone frameworks are promising Kitaev QSL candidates with chemical tunability through ligands that can vary the magnetic coupling and frustration.

KMg4Bi3: A Narrow Band Gap Semiconductor with a Channel Structure.

The creation of new families of intermetallic or Zintl-phase compounds with high-spin orbit elements has attracted a considerable amount of interest due to the presence of unique electronic, magnetic, and topological phenomena in these materials. Here, we establish the synthesis and structural and electronic characterization of KMg4Bi3 single crystals having a new structure type. KMg4Bi3 crystallizes in space group Cmcm having unit cell parameters a = 4.7654(11) Å, b = 15.694(4) Å, and c = 13.4200(30) Å and features an edge-sharing MgBi4 tetrahedral framework that forms cage-like one-dimensional channels around K+ ions. Diffuse reflectance absorption measurements indicate that this material has a narrow band gap of 0.27 eV, which is in close agreement with the electronic structure calculations that predict it to be a trivial insulator. Electronic transport measurements from 80 to 380 K indicate this material behaves like a narrow band gap semiconductor doped to ∼1018 holes/cm-3, with thermopowers of ∼100 µV/K and appreciable magnetoresistance. Electronic structure calculations indicate this material is close to a topological phase transition and becomes a topological insulator when the lattice is uniformly expanded by 3.5%. Overall, this unique structure type expands the landscape of potential quantum materials.

Arginine Acts as both Co-Solvent and Catalyst in Regioselective Eutectic-Mediated Dimerization of Levulinic Acid.

A simple, solvent-free arginine-catalyzed aldol dimerization of levulinic acid was achieved via the simultaneous formation of a eutectic mixture. Dimers of levulinic acid are valued as biomass-derived fine chemical precursors, with potential to upgrade to bio-jet fuels or N-containing functional chemicals. Typically, these dimers are produced as isomeric mixtures using high temperatures and a variety of solid inorganic catalysts or mineral acids. In this study, an organocatalytic and regioselective dimerization was achieved at 22 % conversion on either a bench or kilogram scale using mild temperatures and only L-arginine as both a co-solvent and catalyst. The intricate H-bonding network comprising the eutectic solvent was harnessed to produce only one product, minimizing side reactivity and preserving the reactants for recycling.

Z-selective dimerization of terminal alkynes by a (PNNP)FeII complex.

A tetradentate bis(amido)bis(phosphine) FeII complex, (PNNP)Fe, is shown to activate the terminal C-H bond of aryl alkynes across its Fe-Namide bonds. (PNNP)Fe is also shown to catalytically dimerize terminal aryl alkynes to produce 1,3-enynes with Z : E ratios as high as 96 : 4 with yields up to 95% and loadings as low as 1 mol% at 30 °C in 2 h. A plausible metal-ligand cooperative mechanism invoking a vinylidene intermediate is proposed.

Chiral Viologen-Derived Water-Stable Small Band Gap Lead Halides: Synthesis, Characterization, and Optical Properties.

Chiral organic-inorganic metal halides (OIMHs) are attractive for their potential applications in chiral optoelectronics and spintronics, such as circular polarized light emitters, detectors, and chiral-induced spin selectivity. Here, we report three pairs of chiral OIMHs with great water stability constructed from chiral viologens. These OIMHs contain either 1D or 0D structures, however, with small band gaps around 2 eV. Circular dichroism (CD) spectroscopy on transparent thin films of two OIMH pairs showed a wide CD response covering most of the visible light range. Although the chiral center is not directly attached to the pyridinium in these chiral viologens, the chirality is still successfully transferred into both the band gap and the exciton absorption ranges. Liquid and solid CD studies of the chiral viologens further indicate that the chiral induction inside these OIMHs is possibly through chiral crystallization. This work demonstrated the design strategy of water-stable, small band gap chiral OIMHs through chiral viologens. These low-dimensional chiral materials may provide an interesting system to investigate chiral induction, and their broad CD response may enable their potential application as circular photodetectors with a wide detection range.

Crystallographic Disorder and Strong Magnetic Anisotropy in Dy3Pt2Sb4.48.

We report the crystal growth and characterization of a rare-earth-containing material, Dy3.00(1)Pt2Sb4.48(2). This compound possesses a similar structure to the previously reported Y3Pt4Ge6, but it lacks two layers of Pt atoms. Crystallographic disorder was found in Dy3.00(1)Pt2Sb4.48(2). Additionally, the Dy-Dy framework was found to have both square net and triangular lattices. Dy3.00(1)Pt2Sb4.48(2)8 was determined to be antiferromagnetically ordered around ∼15 K while a competing antiferromagnetic sublattice also exists at lower temperature. Strong magnetic anisotropy was observed, and several metamagnetic transitions were seen in the hysteresis loops. Furthermore, the Curie-Weiss fitting revealed an unusually small effective moment of Dy, which is far below the expected value of Dy3+ (10.65 µB). This material might provide a new platform to study the relationship between crystallographic disorder and magnetism.

Engineering the reductive tricarboxylic acid pathway in Aureobasidium pullulans for enhanced biosynthesis of poly-L-malic acid.

Aureobasidium pullulans produced poly-L-malic acid (PMA) as the main metabolite in fermentation but with relatively low productivity and yield limiting its industrial application. In this study, A. pullulans ZX-10 was engineered to overexpress cytosolic malate dehydrogenase (MDH) and pyruvate carboxylase (PYC) and PMA synthetase (PMS) using a high-copy yeast episomal plasmid with the gpdA promoter from Aspergillus nidulans. Overexpressing endogenous PMS and heterologous MDH and PYC from Aspergillus oryzae respectively increased PMA production by 19 % - 37 % (0.64 - 0.74 g/g vs. 0.54 g/g for wild type) in shake-flask fermentations, demonstrating the importance of the reductive tricarboxylic acid (rTCA) pathway in PMA biosynthesis. A. pullulans co-expressing MDH and PYC produced 96.7 g/L PMA at 0.90 g/L∙h and 0.68 g/g glucose in fed-batch fermentation, which were among the highest yield and productivity reported. The engineered A. pullulans with enhanced rTCA pathway is advantageous and promising for PMA production.

Ligand-Centered Photocatalytic Hydrogen Production in an Axially Capped Rh2(II,II) Paddlewheel Complex with Red Light.

A new series of Rh2(II,II) complexes with the formula cis-[Rh2(DTolF)2(bpnp)(L)]2+, where bpnp = 2,7-bis(2-pyridyl)-1,8-naphthyridine, DTolF = N,N'-di(p-tolyl) formamidinate, and L = pdz (pyridazine; 2), cinn (cinnoline; 3), and bncn (benzo[c]cinnoline; 4), were synthesized from the precursor cis-[Rh2(DTolF)2(bpnp)(CH3CN)2]2+ (1). The first reduction couple in 2-4 is localized on the bpnp ligand at approximately -0.52 V vs Ag/AgCl in CH3CN (0.1 M TBAPF6), followed by reduction of the corresponding diazine ligand. Complex 1 exhibits a Rh2(δ*)/DTolF → bpnp(π*) metal/ligand-to-ligand charge-transfer (1ML-LCT) absorption with a maximum at 767 nm (ε = 1800 M-1 cm-1). This transition is also present in the spectra of 2-4, overlaid with the Rh2(δ*)/DTolF → L(π*) 1ML-LCT bands at 516 nm in 2 (L = pdz), 640 nm in 3 (L = cinn), and 721 nm in 4 (L = bncn). Complexes 2 and 3 exhibit Rh2(δ*)/DTolF → bpnp 3ML-LCT excited states with lifetimes, τ, of 3 and 5 ns, respectively, in CH3CN, whereas the lowest energy 3ML-LCT state in 4 is Rh2(δ*)/DTolF → bncn in nature with τ = 1 ns. Irradiation of 4 with 670 nm light in DMF in the presence of 0.1 M TsOH (p-toluene sulfonic acid) and 30 mM BNAH (1-benzyl-1,4-dihydronicotinamide) results in the production of H2 with a turnover number (TON) of 16 over 24 h. The axial capping of the Rh2(II,II) bimetallic core with the bpnp ligand prevents the formation of an Rh-H hydride intermediate. These results show that the observed photocatalytic reactivity is localized on the bncn ligand, representing the first example of ligand-centered H2 production.

C-N Bond Formation at Discrete CuIII-Aryl Complexes.

Copper(III) aryl species are widely proposed as intermediates in Cu-catalyzed C-C and C-heteroatom bond formation reactions. Despite their wide utility, mechanistic aspects of C-heteroatom formation at CuIII centers as well as factors that lead to byproducts, e.g., Ar-H, Ar-Ar, remain elusive due to the rarity of discrete CuIII-Ar complexes. Herein, we report the synthesis and reactivity of a series of CuII and CuIII aryl complexes that closely mimic the intermediates in Cu-catalyzed C-N coupling reactions. Copper(II) aryl complexes [TBA][LCuII-ArR] were synthesized via the treatment of CuII with a range of aryl donors, such as ZnAr2R, TMS-ArR, and ArR-Bpin. Oxidation of [TBA][LCuII-ArR] produces formal copper(III) aryl complexes LCuIII-ArR. Treatment of copper(III) aryl complexes with neutral nitrogen nucleophiles produces the C-N coupling product in up to 64% yield, along with commonly observed byproducts, such as Ar-H and Ar-Ar. Hammett analysis of the C-N bond formation performed with various N-nucleophiles shows a ρ value of -1.66, consistent with the electrophilic character of LCuIII-ArR. We propose mechanisms for common side reactions in Cu-catalyzed coupling reactions that lead to the formation of Ar-Ar and Ar-H.

Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems.

We describe the preparation, dynamic, assembly characteristics of vase-shaped basket 13- along with its ability to form an inclusion complex with anticancer drug mitoxantrone in abiotic and biotic systems. This novel cavitand has a deep nonpolar pocket consisting of three naphthalimide sides fused to a bicyclic platform at the bottom while carrying polar glycines at the top. The results of 1 H Nuclear Magnetic Resonance (NMR), 1 H NMR Chemical Exchange Saturation Transfer (CEST), Calorimetry, Hybrid Replica Exchange Molecular Dynamics (REMD), and Microcrystal Electron Diffraction (MicroED) measurements are in line with 1 forming dimer [12 ]6- , to be in equilibrium with monomers 1(R) 3- (relaxed) and 1(S) 3- (squeezed). Through simultaneous line-shape analysis of 1 H NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1(R) 3- includes anticancer drug mitoxantrone (MTO2+ ) in its pocket to give stable binary complex [MTO⊂1]- (Kd =2.1 µM) that can be precipitated in vitro with UV light or pH as stimuli. Both in vitro and in vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity in vitro. With well-characterized internal dynamics and dimerization, the ability to include mitoxantrone, and biocompatibility, the stage is set to develop sequestering agents from deep-cavity baskets.

Nitrite Formation at a Diiron Dinitrosyl Complex.

Pathogenic bacteria employ iron-containing enzymes to detoxify nitric oxide (NO•) produced by mammals as part of their immune response. Two classes of diiron proteins, flavodiiron nitric oxide reductases (FNORs) and the hemerythrin-like proteins from mycobacteria (HLPs), are upregulated in bacteria in response to an increased local NO• concentration. While FNORs reduce NO• to nitrous oxide (N2O), the HLPs have been found to either reduce nitrite to NO• (YtfE), or oxidize NO• to nitrite (Mka-HLP). Various structural and functional models of the diiron site in FNORs have been developed over the years. However, the NO• oxidation reactivity of Mka-HLP has yet to be replicated with a synthetic complex. Compared to the FNORs, the coordination environment of the diiron site in Mka-HLP contains one less carboxylate ligand and, therefore, is expected to be more electron-poor. Herein, we synthesized a new diiron complex that models the electron-poor coordination environment of the Mka-HLP diiron site. The diferrous precursor FeIIFeII reacts with NO• to form a diiron dinitrosyl species ({FeNO}72), which is in equilibrium with a mononitrosyl diiron species (FeII{FeNO}7) in solution. Both complexes can be isolated and fully characterized. However, only oxidation of {FeNO}72 produced nitrite in high yield (71%). Our study provides the first model that reproduces the NO• oxidase reactivity of Mka-HLP and suggests intermediacy of an {FeNO}6/{FeNO}7 species.

Design and Synthesis of Cubic K3-2 x Bax SbSe4 Solid Electrolytes for K-O2 Batteries.

Developing K-ion conducting solid-state electrolytes (SSEs) plays a critical role in the safe implementation of potassium batteries. In this work, a chalcogenide-based potassium ion SSE is reported, K3 SbSe4 , which adopts a trigonal structure at room temperature. Single-crystal structural analysis reveals a trigonal-to-cubic phase transition at the low temperature of 50 °C, which is the lowest among similar compounds and thus provides easy access to the cubic phase. The substitution of barium for potassium in K3 SbSe4 leads to the creation of potassium vacancies, expansion of lattice parameters, and a transformation from a trigonal phase to a cubic phase. As a result, the maximum conductivity of K3-2 x Bax SbSe4 reaches around 0.1 mS cm-1 at 40 °C for K2.2 Ba0.4 SbSe4 , which is over two orders of magnitude higher than that of undoped K3 SbSe4 . This novel SSE is successfully employed in a K-O2 battery operating at room temperature where a polymer-laminated K2.2 Ba0.4 SbSe4 pellet serves as a separator between the oxygen cathode and the potassium metal anode. Effective protection of the K metal anode against corrosion caused by O2 is demonstrated.

Synthesis, Characterization, and Reactivity of a (PPP) Pincer-Ligated Manganese Carbonyl Complex: Polarity Reversal Imparted by the Electrophilic Nature of a Planar Mn-P(NR2)2 Fragment.

The bonding interactions of a synthesized pincer-ligated manganese dicarbonyl complex featuring an N-heterocyclic phosphenium (NHP+) central moiety are explored. The pincer ligand [PPP]Cl was coordinated to a manganese center using Mn(CO)5Br and 254 nm light to afford the chlorophosphine complex (PPClP)Mn(CO)2Br (2) as a mixture of halide exchange products and stereoisomers. The target dicarbonyl species (PPP)Mn(CO)2 (3) was prepared by treatment of 2 with 2 equiv of the reductant KC8. Computational investigations and analysis of structural parameters were used to elucidate multiple bonding interactions between the Mn center and the PNHP atom in 3. The generation of a product of formal H2 addition, (PPHP)Mn(CO)2H (4), was achieved through the dehydrogenation of NH3BH3, affording a 2:1 mixture of 4syn:4anti stereoisomers. The nucleophilic nature of the Mn center and the electrophilic nature of the PNHP moiety were demonstrated through hydride addition and protonation of 3 to produce K(THF)2[(PPHP)Mn(CO)2] (6) and (PPClP)Mn(CO)2H (5), respectively. The observed reactivity suggests that 3 is best described as a Mn-I/NHP+ complex, in contrast to pincer-ligated dicarbonyl manganese analogues typically assigned as MnI species.

The Cytotoxic Cardiac Glycoside (-)-Cryptanoside A from the Stems of Cryptolepis dubia and Its Molecular Targets.

A cardiac glycoside epoxide, (-)-cryptanoside A (1), was isolated from the stems of Cryptolepis dubia collected in Laos, for which the complete structure was confirmed by analysis of its spectroscopic and single-crystal X-ray diffraction data, using copper radiation at a low temperature. This cardiac glycoside epoxide exhibited potent cytotoxicity against several human cancer cell lines tested, including HT-29 colon, MDA-MB-231 breast, OVCAR3 and OVCAR5 ovarian cancer, and MDA-MB-435 melanoma cells, with the IC50 values found to be in the range 0.1-0.5 µM, which is comparable with that observed for digoxin. However, it exhibited less potent activity (IC50 1.1 µM) against FT194 benign/nonmalignant human fallopian tube secretory epithelial cells when compared with digoxin (IC50 0.16 µM), indicating its more selective activity toward human cancer versus benign/nonmalignant cells. (-)-Cryptanoside A (1) also inhibited Na+/K+-ATPase activity and increased the expression of Akt and the p65 subunit of NF-κB but did not show any effects on the expression of PI3K. A molecular docking profile showed that (-)-cryptanoside A (1) binds to Na+/K+-ATPase, and thus 1 may directly target Na+/K+-ATPase to mediate its cancer cell cytotoxicity.