Comparing the Electronic Structure of Iron, Cobalt, and Nickel Compounds That Feature a Phosphine-Substituted Bis(imino)pyridine Chelate.

It was recently discovered that (Ph2PPrPDI)Mn (PDI = pyridine diimine) exists as a superposition of low-spin Mn(II) that is supported by a PDI dianion and intermediate-spin Mn(II) that is antiferromagnetically coupled to a triplet PDI dianion, a finding that encouraged the synthesis and electronic structure evaluation of late first row metal variants that feature the same chelate. The addition of Ph2PPrPDI to FeBr2 resulted in bromide dissociation and the formation of [(Ph2PPrPDI)FeBr][Br]. Reduction of this precursor using excess sodium amalgam afforded (Ph2PPrPDI)Fe, which possesses an Fe(II) center that is supported by a dianionic PDI ligand. Similarly, reduction of a premixed solution of Ph2PPrPDI and CoCl2 yielded the cobalt analog, (Ph2PPrPDI)Co. EPR spectroscopy and density functional theory calculations revealed that this compound features a high-spin Co(I) center that is antiferromagnetically coupled to a PDI radical anion. The addition of Ph2PPrPDI to Ni(COD)2 resulted in ligand displacement and the formation of (Ph2PPrPDI)Ni, which was found to possess a pendent phosphine group. Single-crystal X-ray diffraction, CASSCF calculations, and EPR spectroscopy indicate that (Ph2PPrPDI)Ni is best described as having a Ni(II)-PDI2- configuration. The electronic differences between these compounds are highlighted, and a computational analysis of Ph2PPrPDI denticity has revealed the thermodynamic penalties associated with phosphine dissociation from 5-coordinate (Ph2PPrPDI)Mn, (Ph2PPrPDI)Fe, and (Ph2PPrPDI)Co.

Reaction of a Molybdenum Bis(dinitrogen) Complex with Carbon Dioxide: A Combined Experimental and Computational Investigation.

Refluxing Mo(CO)6 in the presence of the phosphine-functionalized α-diimine ligand Ph2PPrDI allowed for substitution and formation of the dicarbonyl complex, (Ph2PPrDI)Mo(CO)2. Oxidation with I2 followed by heating resulted in further CO dissociation and isolation of the corresponding diiodide complex, (Ph2PPrDI)MoI2. Reduction of this complex under a N2 atmosphere afforded the corresponding bis(dinitrogen) complex, (Ph2PPrDI)Mo(N2)2. The solid-state structures of all three compounds were found to feature a tetradentate chelate and cis-monodentate ligands. Notably, the addition of CO2 to (Ph2PPrDI)Mo(N2)2 is proposed to result in head-to-tail CO2 coupling to generate the corresponding metallacycle and ultimately a mixture of (Ph2PPrDI)Mo(CO)2 and the bis(oxo) dimer, [(κ3-Ph2PPrDI)Mo(O)(µ-O)]2. Computational studies have been performed to gain insight into the reaction and evaluate the importance of cis-coordination sites for selective head-to-tail CO2 reductive coupling, CO deinsertion, disproportionation, and stepwise CO2 deinsertion.

Efficient Cobalt Catalyst for Ambient-Temperature Nitrile Dihydroboration, the Elucidation of a Chelate-Assisted Borylation Mechanism, and a New Synthetic Route to Amides.

N,N-Diborylamines have emerged as promising reagents in organic synthesis; however, their efficient preparation and full synthetic utility have yet to be realized. To address both shortcomings, an effective catalyst for nitrile dihydroboration was sought. Heating CoCl2 in the presence of PyEtPDI afforded the six-coordinate Co(II) salt, [(PyEtPDI)CoCl][Cl]. Upon adding 2 equiv of NaEt3BH, hydride transfer to one chelate imine functionality was observed, resulting in the formation of (κ4-N,N,N,N-PyEtIPCHMeNEtPy)Co. Single-crystal X-ray diffraction and density functional theory calculations revealed that this compound possesses a low-spin Co(II) ground state featuring antiferromagnetic coupling to a singly reduced imino(pyridine) moiety. Importantly, (κ4-N,N,N,N-PyEtIPCHMeNEtPy)Co was found to catalyze the dihydroboration of nitriles using HBPin with turnover frequencies of up to 380 h-1 at ambient temperature. Stoichiometric addition experiments revealed that HBPin adds across the Co-Namide bond to generate a hydride intermediate that can react with additional HBPin or nitriles. Computational evaluation of the reaction coordinate revealed that the B-H addition and nitrile insertion steps occur on the antiferromagnetically coupled triplet spin manifold. Interestingly, formation of the borylimine intermediate was found to occur following BPin transfer from the borylated chelate arm to regenerate (κ4-N,N,N,N-PyEtIPCHMeNEtPy)Co. Borylimine reduction is in turn facile and follows the same ligand-assisted borylation pathway. The independent hydroboration of alkyl and aryl imines was also demonstrated at 25 °C. With a series of N,N-diborylamines in hand, their addition to carboxylic acids allowed for the direct synthesis of amides at 120 °C, without the need for an exogenous coupling reagent.

Controlling Proton-Coupled Electron Transfer in Bioinspired Artificial Photosynthetic Relays.

Bioinspired constructs consisting of benzimidazole-phenol moieties bearing N-phenylimines as proton-accepting substituents have been designed to mimic the H-bond network associated with the TyrZ-His190 redox relay in photosystem II. These compounds provide a platform to theoretically and experimentally explore and expand proton-coupled electron transfer (PCET) processes. The models feature H-bonds between the phenol and the nitrogen at the 3-position of the benzimidazole and between the 1 H-benzimidazole proton and the imine nitrogen. Protonation of the benzimidazole and the imine can be unambiguously detected by infrared spectroelectrochemistry (IRSEC) upon oxidation of the phenol. DFT calculations and IRSEC results demonstrate that with sufficiently strong electron-donating groups at the para-position of the N-phenylimine group (e.g., -OCH3 substitution), proton transfer to the imine is exergonic upon phenol oxidation, leading to a one-electron, two-proton (E2PT) product with the imidazole acting as a proton relay. When transfer of the second proton is not sufficiently exergonic (e.g., -CN substitution), a one-electron, one-proton transfer (EPT) product is dominant. Thus, the extent of proton translocation along the H-bond network, either ∼1.6 Å or ∼6.4 Å, can be controlled through imine substitution. Moreover, the H-bond strength between the benzimidazole NH and the imine nitrogen, which is a function of their relative p Ka values, and the redox potential of the phenoxyl radical/phenol couple are linearly correlated with the Hammett constants of the substituents. In all cases, a high potential (∼1 V vs SCE) is observed for the phenoxyl radical/phenol couple. Designing and tuning redox-coupled proton wires is important for understanding bioenergetics and developing novel artificial photosynthetic systems.

Isolation of Mn(I) Compounds Featuring a Reduced Bis(imino)pyridine Chelate and Their Relevance to Electrocatalytic Hydrogen Production.

We report the preparation and electronic structure determination of chelate-reduced Mn(I) compounds that are relevant to electrocatalytic proton reduction mediated by [(Ph2PPrPDI)Mn(CO)][Br]. Reducing [(Ph2PPrPDI)Mn(CO)][Br] with excess Na-Hg afforded a neutral paramagnetic complex, (Ph2PPrPDI)Mn(CO). This compound was found to feature a low spin Mn(I) center and a PDI radical anion as determined by magnetic susceptibility measurement (1.97 µB), EPR spectroscopy ( S = 1/2), and density functional theory calculations. When [(Ph2PPrPDI)Mn(CO)][Br] was reduced with K-Hg, Mn(I) complexes with highly activated CO ligands were obtained. Recrystallization of the reduced product from diethyl ether solution allowed for the isolation of dimeric [(κ4-Ph2PPrPDI)Mn(µ-η1,η1,η2-CO)K(Et2O)]2 (νCO = 1710 cm-1, 1656 cm-1), while methyl tert-butyl ether treatment afforded dimeric [(κ4-Ph2PPrPDI)Mn(µ-η1,η1-CO)K(MTBE)2]2 (νCO = 1695 cm-1, MTBE = methyl tert-butyl ether). Addition of 18-crown-6 to these products, or conducting the K-Hg reduction of [(Ph2PPrPDI)Mn(CO)][Br] in the presence of 18-crown-6, allowed for the isolation of a monomeric example, (κ4-Ph2PPrPDI)Mn(µ-η1,η2-CO)K(18-crown-6) (νCO = 1697 cm-1). All three complexes were found to be diamagnetic and were characterized thoroughly by multinuclear 1D and 2D NMR spectroscopy and single crystal X-ray diffraction. Detailed analysis of the metrical parameters and spectroscopic properties suggest that all three compounds possess a Mn(I) center that is supported by a PDI dianion. Importantly, (κ4-Ph2PPrPDI)Mn(µ-η1,η2-CO)K(18-crown-6) was found to react instantaneously with either HBF4·OEt2 or HOTf to evolve H2 and generate the corresponding Mn(I) complex, [(Ph2PPrPDI)Mn(CO)][BF4] or [(Ph2PPrPDI)Mn(CO)][OTf], respectively. These products are spectroscopically and electrochemically similar to previously reported [(Ph2PPrPDI)Mn(CO)][Br]. It is believed that the mechanism of [(Ph2PPrPDI)Mn(CO)][Br]-mediated proton reduction involves intermediates that are related to the compounds described herein and that their ambient temperature isolation is aided by the redox active nature of Ph2PPrPDI.

Mechanistic Investigation of Bis(imino)pyridine Manganese Catalyzed Carbonyl and Carboxylate Hydrosilylation.

We recently reported a bis(imino)pyridine (or pyridine diimine, PDI) manganese precatalyst, (Ph2PPrPDI)Mn (1), that is active for the hydrosilylation of ketones and dihydrosilylation of esters. In this contribution, we reveal an expanded scope for 1-mediated hydrosilylation and propose two different mechanisms through which catalysis is achieved. Aldehyde hydrosilylation turnover frequencies (TOFs) of up to 4900 min-1 have been realized, the highest reported for first row metal-catalyzed carbonyl hydrosilylation. Additionally, 1 has been shown to mediate formate dihydrosilylation with leading TOFs of up to 330 min-1. Under stoichiometric and catalytic conditions, addition of PhSiH3 to (Ph2PPrPDI)Mn was found to result in partial conversion to a new diamagnetic hydride compound. Independent preparation of (Ph2PPrPDI)MnH (2) was achieved upon adding NaEt3BH to (Ph2PPrPDI)MnCl2 and single-crystal X-ray diffraction analysis revealed this complex to possess a capped trigonal bipyramidal solid-state geometry. When 2,2,2-trifluoroacetophenone was added to 1, radical transfer yielded (Ph2PPrPDI·)Mn(OC·(Ph)(CF3)) (3), which undergoes intermolecular C-C bond formation to produce the respective Mn(II) dimer, [(µ-O,Npy-4-OC(CF3)(Ph)-4-H-Ph2PPrPDI)Mn]2 (4). Upon finding 3 to be inefficient and 4 to be inactive, kinetic trials were conducted to elucidate the mechanisms of 1- and 2-mediated hydrosilylation. Varying the concentration of 1, substrate, and PhSiH3 revealed a first order dependence on each reagent. Furthermore, a kinetic isotope effect (KIE) of 2.2 ± 0.1 was observed for 1-catalyzed hydrosilylation of diisopropyl ketone, while a KIE of 4.2 ± 0.6 was determined using 2, suggesting 1 and 2 operate through different mechanisms. Although kinetic trials reveal 1 to be the more active precatalyst for carbonyl hydrosilylation, a concurrent 2-mediated pathway is more efficient for carboxylate hydrosilylation. Considering these observations, 1-catalyzed hydrosilylation is believed to proceed through a modified Ojima mechanism, while 2-mediated hydrosilylation occurs via insertion.

A nickel phosphine complex as a fast and efficient hydrogen production catalyst.

Here we report the electrocatalytic reduction of protons to hydrogen by a novel S2P2 coordinated nickel complex, [Ni(bdt)(dppf)] (bdt = 1,2-benzenedithiolate, dppf = 1,1'-bis(diphenylphosphino)ferrocene). The catalysis is fast and efficient with a turnover frequency of 1240 s(-1) and an overpotential of only 265 mV for half activity at low acid concentrations. Furthermore, catalysis is possible using a weak acid, and the complex is stable for at least 4 h in acidic solution. Calculations of the system carried out at the density functional level of theory (DFT) are consistent with a mechanism for catalysis in which both protonations take place at the nickel center.

Substantial production of drosophilin A methyl ether (tetrachloro-1,4-dimethoxybenzene) by the lignicolous basidiomycete Phellinus badius in the heartwood of mesquite (Prosopis juliflora) trees.

Toxic organohalogen pollutants produced as by-products of industrial processes, such as chloroform and polychlorinated dibenzo-p-dioxins, also have significant natural sources. A substantial terrestrial source of halogenated organics originates from fungal decay of wood and leaf litter. Here we show that the lignicolous basidiomycete Phellinus badius deposits up to 30,000 mg of the halogenated metabolite drosophilin A methyl ether (DAME, tetrachloro-1,4-dimethoxybenzene) per kilogram of decayed heartwood in the mesquite Prosopis juliflora. DAME occurs as clusters of glassy crystals up to 1 mm long within the decayed heartwood. In addition, the Phellinus badius basidiocarps contain an average of 24,000 mg DAME/kg dried fruiting body, testifying to the significant translocation and accumulation of Cl accompanied by DAME biosynthesis. The high DAME concentrations attest to the substantial Cl content of the heartwood, which averages near 5,000 ppm, with Cl/K near 1:1, consistent with an inorganic chloride precursor. Phellinus badius has a circumglobal distribution in the tropics and subtropics, where it is widely distributed on hardwoods and commonly associated with decay of mesquite. There is the potential for extensive DAME formation within decayed heartwood worldwide given the extensive range of Phellinus badius and its propensity to form DAME within mesquites. Further, DAME production is not limited to Phellinus badius but occurs in a range of lignicolous basidiomycetes, suggesting a significant natural reservoir for this chloroaromatic with potential environmental implications.

Conversion of Carbon Dioxide to Methanol Using a C-H Activated Bis(imino)pyridine Molybdenum Hydroboration Catalyst.

Using a multistep synthetic pathway, a bis(imino)pyridine (or pyridine diimine, PDI) molybdenum catalyst for the selective conversion of carbon dioxide into methanol has been developed. Starting from ((Ph2PPr)PDI)Mo(CO), I2 addition afforded [((Ph2PPr)PDI)MoI(CO)][I], which features a seven-coordinate Mo(II) center. Heating this complex to 100 °C under vacuum resulted in CO loss and the formation of [((Ph2PPr)PDI)MoI][I]. Reduction of [((Ph2PPr)PDI)MoI][I] in the presence of excess K/Hg yielded (κ(6)-P,N,N,N,C,P-(Ph2PPr)PDI)MoH following methylene group C-H activation at the α-position of one PDI imine substituent. The addition of CO2 to (κ(6)-P,N,N,N,C,P-(Ph2PPr)PDI)MoH resulted in facile insertion to generate the respective η(1)-formate complex, (κ(6)-P,N,N,N,C,P-(Ph2PPr)PDI)Mo(OCOH). When low pressures of CO2 were added to solutions of (κ(6)-P,N,N,N,C,P-(Ph2PPr)PDI)MoH containing pinacolborane, the selective formation of H3COBPin and O(BPin)2 was observed along with precatalyst regeneration. When HBPin was limited, H2C(OBPin)2 was observed as an intermediate and (κ(6)-P,N,N,N,C,P-(Ph2PPr)PDI)Mo(OCOH) remained present throughout CO2 reduction. The hydroboration of CO2 to H3COBPin was optimized and 97% HBPin utilization by 0.1 mol % (κ(6)-P,N,N,N,C,P-(Ph2PPr)PDI)MoH was demonstrated over 8 h at 90 °C, resulting in a methoxide formation turnover frequency (TOF) of 40.4 h(-1) (B-H utilization TOF = 121.2 h(-1)). Hydrolysis of the products and distillation at 65 °C allowed for MeOH isolation. The mechanism of (κ(6)-P,N,N,N,C,P-(Ph2PPr)PDI)MoH mediated CO2 hydroboration is presented in the context of these experimental observations. Notably, (κ(6)-P,N,N,N,C,P-(Ph2PPr)PDI)MoH is the first Mo hydroboration catalyst capable of converting CO2 to MeOH, and the importance of this study as it relates to previously described catalysts is discussed.

A Pentacoordinate Mn(II) Precatalyst That Exhibits Notable Aldehyde and Ketone Hydrosilylation Turnover Frequencies.

Heating (THF)2MnCl2 in the presence of the pyridine-substituted bis(imino)pyridine ligand, (PyEt)PDI, allowed preparation of the respective dihalide complex, ((PyEt)PDI)MnCl2. Reduction of this precursor using excess Na/Hg resulted in deprotonation of the chelate methyl groups to yield the bis(enamide)tris(pyridine)-supported product, (κ(5)-N,N,N,N,N-(PyEt)PDEA)Mn. This complex was characterized by single-crystal X-ray diffraction and found to possess an intermediate-spin (S = (3)/2) Mn(II) center by the Evans method and electron paramagnetic resonance spectroscopy. Furthermore, (κ(5)-N,N,N,N,N-(PyEt)PDEA)Mn was determined to be an effective precatalyst for the hydrosilylation of aldehydes and ketones, exhibiting turnover frequencies of up to 2475 min(-1) when employed under solvent-free conditions. This optimization allowed for isolation of the respective alcohols and, in two cases, the partially reacted silyl ethers, PhSiH(OR)2 [R = Cy and CH(Me)((n)Bu)]. The aldehyde hydrosilylation activity observed for (κ(5)-N,N,N,N,N-(PyEt)PDEA)Mn renders it one of the most efficient first-row transition metal catalysts for this transformation reported to date.

Carbon Dioxide Promoted H(+) Reduction Using a Bis(imino)pyridine Manganese Electrocatalyst.

Heating a 1:1 mixture of (CO)5MnBr and the phosphine-substituted pyridine diimine ligand, (Ph2PPr)PDI, in THF at 65 °C for 24 h afforded the diamagnetic complex [((Ph2PPr)PDI)Mn(CO)][Br] (1). Higher temperatures and longer reaction times resulted in bromide displacement of the remaining carbonyl ligand and the formation of paramagnetic ((Ph2PPr)PDI)MnBr (2). The molecular structure of 1 was determined by single crystal X-ray diffraction, and density functional theory (DFT) calculations indicate that this complex is best described as low-spin Mn(I) bound to a neutral (Ph2PPr)PDI chelating ligand. The redox properties of 1 and 2 were investigated by cyclic voltammetry (CV), and each complex was tested for electrocatalytic activity in the presence of both CO2 and Brønsted acids. Although electrocatalytic response was not observed when CO2, H2O, or MeOH was added to 1 individually, the addition of H2O or MeOH to CO2-saturated acetonitrile solutions of 1 afforded voltammetric responses featuring increased current density as a function of proton source concentration (icat/ip up to 2.4 for H2O or 4.2 for MeOH at scan rates of 0.1 V/s). Bulk electrolysis using 5 mM 1 and 1.05 M MeOH in acetonitrile at -2.2 V vs Fc(+/0) over the course of 47 min gave H2 as the only detectable product with a Faradaic efficiency of 96.7%. Electrochemical experiments indicate that CO2 promotes 1-mediated H2 production by lowering apparent pH. While evaluating 2 for electrocatalytic activity, this complex was found to decompose rapidly in the presence of acid. Although modest H(+) reduction activity was realized, the experiments described herein indicate that care must be taken when evaluating Mn complexes for electrocatalytic CO2 reduction.

Antineoplastic agents. 599. Total synthesis of dolastatin 16.

The first 23-step total synthesis of the cyclodepsipeptide dolastatin 16 (1) has been achieved. Synthesis of the dolaphenvaline and dolamethylleuine amino acid units using simplified methods improved the overall efficiency. The formation of the 25-membered macrocycle employing lactonization with 2-methyl-6-nitrobenzoic anhydride completed a key step in the synthesis. Regrettably, the synthetic dolastatin 16 (1), while otherwise identical (by X-ray crystal structure and spectral analyses) with the natural product, did not reproduce the powerful (nanomolar) cancer cell growth inhibition displayed by the natural isolate. Presumably this result can be attributed to conformation(s) of the synthetic dolastatin 16 (1) or to a chemically undetected component isolated with the natural product.

A highly active manganese precatalyst for the hydrosilylation of ketones and esters.

The reduction of ((Ph2PPr)PDI)MnCl2 allowed the preparation of the formally zerovalent complex, ((Ph2PPr)PDI)Mn, which features a pentadentate bis(imino)pyridine chelate. This complex is a highly active precatalyst for the hydrosilylation of ketones, exhibiting TOFs of up to 76,800 h(-1) in the absence of solvent. Loadings as low as 0.01 mol % were employed, and ((Ph2PPr)PDI)Mn was found to mediate the atom-efficient utilization of Si-H bonds to form quaternary silane products. ((Ph2PPr)PDI)Mn was also shown to catalyze the dihydrosilylation of esters following cleavage of the substrate acyl C-O bond. Electronic structure investigation of ((Ph2PPr)PDI)Mn revealed that this complex possesses an unpaired electron on the metal center, rendering it likely that catalysis takes place following electron transfer to the incoming carbonyl substituent.

Preparation and hydrosilylation activity of a molybdenum carbonyl complex that features a pentadentate bis(imino)pyridine ligand.

Attempts to prepare low-valent molybdenum complexes that feature a pentadentate 2,6-bis(imino)pyridine (or pyridine diimine, PDI) chelate allowed for the isolation of two different products. Refluxing Mo(CO)6 with the pyridine-substituted PDI ligand, (PyEt)PDI, resulted in carbonyl ligand substitution and formation of the respective bis(ligand) compound ((PyEt)PDI)2Mo (1). This complex was investigated by single-crystal X-ray diffraction, and density functional theory calculations indicated that 1 possesses a Mo(0) center that back-bonds into the π*-orbitals of the unreduced PDI ligands. Heating an equimolar solution of Mo(CO)6 and the phosphine-substituted PDI ligand, (Ph2PPr)PDI, to 120 °C allowed for the preparation of ((Ph2PPr)PDI)Mo(CO) (2), which is supported by a κ(5)-N,N,N,P,P-(Ph2PPr)PDI chelate. Notably, 1 and 2 have been found to catalyze the hydrosilylation of benzaldehyde at 90 °C, and the optimization of 2-catalyzed aldehyde hydrosilylation at this temperature afforded turnover frequencies of up to 330 h(-1). Considering additional experimental observations, the potential mechanism of 2-mediated carbonyl hydrosilylation is discussed.

Catalytic hydrogen evolution by Fe(II) carbonyls featuring a dithiolate and a chelating phosphine.

Two pentacoordinate mononuclear iron carbonyls of the form (bdt)Fe(CO)P2 [bdt = benzene-1,2-dithiolate; P2 = 1,1'-diphenylphosphinoferrocene (1) or methyl-2-{bis(diphenylphosphinomethyl)amino}acetate (2)] were prepared as functional, biomimetic models for the distal iron (Fe(d)) of the active site of [FeFe]-hydrogenase. X-ray crystal structures of the complexes reveal that, despite similar ν(CO) stretching band frequencies, the two complexes have different coordination geometries. In X-ray crystal structures, the iron center of 1 is in a distorted trigonal bipyramidal arrangement, and that of 2 is in a distorted square pyramidal geometry. Electrochemical investigation shows that both complexes catalyze electrochemical proton reduction from acetic acid at mild overpotential, 0.17 and 0.38 V for 1 and 2, respectively. Although coordinatively unsaturated, the complexes display only weak, reversible binding affinity toward CO (1 bar). However, ligand centered protonation by the strong acid, HBF4·OEt2, triggers quantitative CO uptake by 1 to form a dicarbonyl analogue [1(H)-CO](+) that can be reversibly converted back to 1 by deprotonation using NEt3. Both crystallographically determined distances within the bdt ligand and density functional theory calculations suggest that the iron centers in both 1 and 2 are partially reduced at the expense of partial oxidation of the bdt ligand. Ligand protonation interrupts this extensive electronic delocalization between the Fe and bdt making 1(H)(+) susceptible to external CO binding.

Antineoplastic agents. 595. Structural modifications of betulin and the X-ray crystal structure of an unusual betulin amine dimer.

The lupane-type triterpene betulin (1) has been subjected to a series of structural modifications for the purpose of evaluating resultant cancer cell growth inhibitory activity. The reaction sequence 7→11→12 was especially noteworthy in providing a betulin-derived amine dimer. Other unexpected synthetic results included the 11 and 13/14→17 conversions, which yielded an imidazo derivative. X-ray crystal structures of dimer 12 and intermediate 25 are reported. All of the betulin modifications were examined for anticancer activity against the P388 murine and human cell lines. Significant cancer cell growth inhibition was found for 4, 8, 9, 15/16, 19, 20, 24, and 26, which further defines the utility of the betulin scaffold.

Multi PCET in symmetrically substituted benzimidazoles.

Proton-coupled electron transfer (PCET) reactions depend on the hydrogen-bond connectivity between sites of proton donors and acceptors. The 2-(2'-hydroxyphenyl) benzimidazole (BIP) based systems, which mimic the natural TyrZ-His190 pair of Photosystem II, have been useful for understanding the associated PCET process triggered by one-electron oxidation of the phenol. Substitution of the benzimidazole by an appropriate terminal proton acceptor (TPA) group allows for two-proton translocations. However, the prototropic properties of substituted benzimidazole rings and rotation around the bond linking the phenol and the benzimidazole can lead to isomers that interrupt the intramolecular hydrogen-bonded network and thereby prevent a second proton translocation. Herein, a strategic symmetrization of a benzimidazole based system with two identical TPAs yields an uninterrupted network of intramolecular hydrogen bonds regardless of the isomeric form. NMR data confirms the presence of a single isomeric form in the disubstituted system but not in the monosubstituted system in certain solvents. Infrared spectroelectrochemistry demonstrates a two-proton transfer process associated with the oxidation of the phenol occurring at a lower redox potential in the disubstituted system relative to its monosubstituted analogue. Computational studies support these findings and show that the disubstituted system stabilizes the oxidized two-proton transfer product through the formation of a bifurcated hydrogen bond. Considering the prototropic properties of the benzimidazole heterocycle in the context of multiple PCET will improve the next generation of novel, bioinspired constructs built by concatenated units of benzimidazoles, thus allowing proton translocations at nanoscale length.

2-Fluoro-4-(meth-oxy-carbon-yl)benzoic acid.

In the crystal of the title compound, C(9)H(7)FO(4), classical carboxylate inversion dimers are linked by pairs of O-H⋯O hydrogen bonds. The packing is consolidated by C-H⋯F and C-H⋯O interactions. The benzene ring and the methoxycarbonyl group are nearly coplanar, with a dihedral angle of 1.5 (3)° between them, whereas the carboxyl group has a dihedral angle of 20.2 (4)° with respect to the benzene ring.

Methyl (Z)-2-chloro-3-(2-methoxy-carbonyl-phen-yl)prop-2-enoate.

In the title compound, C(12)H(11)ClO(4), the propenoate C=C bond is in the Z configuration. The propenoate C=O and C=C groups are essentially coplanar [C=C-C=O torsion angle = 172.4 (3)°] with the O atom synperiplanar to the Cl atom. However, the π systems of the aromatic ring and chloro-propenoate substituent are not coplanar; the corresponding dihedral angle is 51.5 (1)°. The noncoplanarity is likely due to steric inter-actions between the propenoate H atom and the ortho-methoxy-carbonyl group on the aromatic ring. Even in the observed noncoplanar conformation, the ortho C=O to H distance (2.40 Å) is less than the sum of the van der Waals radii of O and H (2.65 Å).

Solution and Solid-State Characterization of PbSe Precursors.

The addition of lead to diphenyl diselenide in ethylenediamine (en) or pyridine (py) allowed for the observation of the solvento complexes, (en)Pb(SePh)2 or (py)2Pb(SePh)2, respectively. Performing this reaction in dimethyl sulfoxide and subsequent crystallization was found to afford Pb(SePh)2. Inductively coupled plasma optical emission spectroscopy revealed a 1:2 lead to selenium ratio for all three complexes. Nuclear magnetic resonance spectroscopy confirms that Pb(SePh)2 is readily solubilized by ethylenediamine, and electrospray ionization mass spectrometry supports the presence of Pb(SePh)2 moieties in solution. Single-crystal X-ray diffraction analysis of the pyridine adduct, (py)2Pb(SePh)2, revealed a seesaw molecular geometry featuring equatorial phenylselenolate ligands. Crystals of Pb(SePh)2 grown from dimethyl sulfoxide revealed one-dimensional polymeric chains of Pb(SePh)2. We believe that the lead(II) phenylselenolate complexes form via an oxidative addition reaction.