Water oxidation can lead to a sustainable source of energy, but for water oxidation catalysts to be economical they must use earth abundant metals. We report here 2:1 6,6'-dihydroxybipyridine (6,6'-dhbp)/copper complexes that are capable of electrocatalytic water oxidation in aqueous base (pH = 10-14). Two crystal structures of the complex that contains 6,6'-dhbp and copper(II) in a ratio of 2:1 (complex 1) are presented at different protonation states. The thermodynamic acid dissociation constants were measured for complex 1, and these show that the complex is fully deprotonated above pH = 8.3 (i.e., under water oxidation conditions). CW-EPR, ENDOR, and HYSCORE spectroscopy confirmed that the 6,6'-dhbp ligand is bound to the copper ion over a wide pH range which shows how pH influences precatalyst structure. Additional copper(II) complexes were synthesized from the ligands 4,4'-dhbp (complex 2) and 6,6'-dimethoxybipyridine (complexes 3 and 4). A zinc complex of 6,6'-dhbp was also synthesized (complex 5). Crystal structures are reported for 1 (in two protonation states), 3, 4, and 5. Water oxidation studies using several of the above compounds (1, 2, 4, and 5) at pH = 12.6 have illustrated that both copper and proximal OH groups are necessary for water oxidation at a low overpotential. Our most active catalyst 1 was found to have an overpotential of 477 mV for water oxidation at a moderate rate of kcat = 0.356 s(-1) with a competing irreversible oxidation event at a rate of 1.082 s(-1). Furthermore, our combined work supports previous observations in which OH/O(-) groups on the bipyridine rings can hydrogen bond with metal bound substrate, support unusual binding modes, and potentially facilitate proton coupled electron transfer.

Metallo prodrugs that take advantage of the inherent acidity surrounding cancer cells have yet to be developed. We report a new class of pH-activated metallo prodrugs (pHAMPs) that are activated by light- and pH-triggered ligand dissociation. These ruthenium complexes take advantage of a key characteristic of cancer cells and hypoxic solid tumors (acidity) that can be exploited to lessen the side effects of chemotherapy. Five ruthenium complexes of the type [(N,N)Ru(PL)] were synthesized, fully characterized, and tested for cytotoxicity in cell culture (1: N,N = 2,2'-bipyridine (bipy) and PL, the photolabile ligand, = 6,6'-dihydroxybipyridine (6,6'-dhbp); 2: N,N = 1,10-phenanthroline (phen) and PL = 6,6'-dhbp; 3: N,N = 2,3-dihydro-[1,4]dioxino[2,3-f][1,10]phenanthroline (dop) and PL = 6,6'-dhbp; 4: N,N = bipy and PL = 4,4'-dimethyl-6,6'-dihydroxybipyridine (dmdhbp); 5: N,N = 1,10-phenanthroline (phen) and PL = 4,4'-dihydroxybipyridine (4,4'-dhbp). The thermodynamic acidity of these complexes was measured in terms of two pK values for conversion from the acidic form (X) to the basic form (X) by removal of two protons. Single-crystal X-ray diffraction data is discussed for 2, 2, 3, 4, and 5. All complexes except 5 showed measurable photodissociation with blue light (λ = 450 nm). For complexes 1-4 and their deprotonated analogues (1-4), the protonated form (at pH 5) consistently gave faster rates of photodissociation and larger quantum yields for the photoproduct, [(N,N)Ru(HO)]. This shows that low pH can lead to greater rates of photodissociation. Cytotoxicity studies with 1-5 showed that complex 3 is the most cytotoxic complex of this series with IC values as low as 4 μM (with blue light) versus two breast cancer cell lines. Complex 3 is also selectively cytotoxic, with sevenfold higher toxicity toward cancerous versus normal breast cells. Phototoxicity indices with 3 were as high as 120, which shows that dark toxicity is avoided. The key difference between complex 3 and the other complexes tested appears to be higher uptake of the complex as measured by inductively coupled plasma mass spectrometry, and a more hydrophobic complex as compared to 1, which may enhance uptake. These complexes demonstrate proof of concept for dual activation by both low pH and blue light, thus establishing that a pHAMP approach can be used for selective targeting of cancer cells.

A series of substituted 9-borafluorenes were studied both experimentally and computationally in order to assess substituent effects on the optical and electronic properties and the stability of 9-borafluorenes. The previously unknown 9-substituted-9-borafluorenes Mes F BF (MesF = 2,4,6-tris­(trifluoromethyl)­phenyl), TipBF­(OMe) 2 (Tip = 2,4,6-tris­(triisopropyl)­phenyl, (OMe)2= methoxy at the borafluorene 3 and 6 positions), and i Pr 2 NBF (iPr2N = diisopropylamino) were synthesized and structurally characterized. The previously reported TipBF, ClBF (9-chloro-9-borafluorene) and t BuOBF (9-(tert-butoxy)-9-borafluorene) were also included in this study. All of the aryl borafluorenes (TipBF, TipBF­(OMe) 2 , Mes F BF), and t BuOBF are moderately air-stable. Both i Pr 2 NBF and ClBF degrade rapidly in air. Cyclic voltammogram measurements and density functional theory (DFT) calculations reveal that (a) borafluorenes have higher electron affinities relative to comparable boranes and (b) substituents have a strong influence on the lowest unoccupied molecular orbital (LUMO) levels of borafluorenes but less influence over the highest occupied molecular orbital (HOMO) levels. The DFT calculations show that, in general, borafluorenes exhibit low electron reorganization energies, a predictor of good electron mobility. However, the MesF group, which is finding popularity as a stabilizing group in borane chemistry, significantly increases the electron reorganization energy of Mes F BF compared to the other borafluorenes. The Lewis acidities of the borafluorenes were probed using Et3PO as a Lewis base (the Gutmann–Beckett method) and found to be dictated primarily by steric considerations. Calculated fluoride affinities (Lewis acidities) correlate with the LUMO energies of the borafluorenes. UV–visible and fluorescence spectroscopic measurements showed that compared to the Tip substituent, the MesF, Cl, and methoxy groups only cause subtle changes to the optical properties of the borafluorenes. The absorption spectra of both i Pr 2 NBF and t BuOBF are blue-shifted due to substituent π-backbonding with the p-orbital on boron. The results of this study provide insights into substituent effects on conjugated boron systems and will help in the design of future boron containing materials.

Hydrogenation reactions can be used to store energy in chemical bonds, and if these reactions are reversible, that energy can be released on demand. Some of the most effective transition metal catalysts for CO2 hydrogenation have featured pyridin-2-ol-based ligands (e.g., 6,6′-dihydroxybipyridine (6,6′-dhbp)) for both their proton-responsive features and for metal–ligand bifunctional catalysis. We aimed to compare bidentate pyridin-2-ol based ligands with a new scaffold featuring an N-heterocyclic carbene (NHC) bound to pyridin-2-ol. Toward this aim, we have synthesized a series of [Cp*Ir(NHC-pyOR)Cl]OTf complexes where R = tBu (1), H (2), or Me (3). For comparison, we tested analogous bipy-derived iridium complexes as catalysts, specifically [Cp*Ir(6,6′-dxbp)Cl]OTf, where x = hydroxy (4Ir) or methoxy (5Ir); 4Ir was reported previously, but 5Ir is new. The analogous ruthenium complexes were also tested using [(η6-cymene)Ru(6,6′-dxbp)Cl]OTf, where x = hydroxy (4Ru) or methoxy (5Ru); 4Ru and 5Ru were both reported previously. All new complexes were fully characterized by spectroscopic and analytical methods and by single-crystal X-ray diffraction for 1, 2, 3, 5Ir, and for two [Ag(NHC-pyOR)2]OTf complexes 6 (R = tBu) and 7 (R = Me). The aqueous catalytic studies of both CO2 hydrogenation and formic acid dehydrogenation were performed with catalysts 1–5. In general, NHC-pyOR complexes 1–3 were modest precatalysts for both reactions. NHC complexes 1–3 all underwent transformations under basic CO2 hydrogenation conditions, and for 3, we trapped a product of its transformation, 3SP, which we characterized crystallographically. For CO2 hydrogenation with base and dxbp-based catalysts, we observed that x = hydroxy (4Ir) is 5–8 times more active than x = methoxy (5Ir). Notably, ruthenium complex 4Ru showed 95% of the activity of 4Ir. For formic acid dehydrogenation, the trends were quite different with catalytic activity showing 4Ir ≫ 4Ru and 4Ir ≈ 5Ir. Secondary coordination sphere effects are important under basic hydrogenation conditions where the OH groups of 6,6′-dhbp are deprotonated and alkali metals can bind and help to activate CO2. Computational DFT studies have confirmed these trends and have been used to study the mechanisms of both CO2 hydrogenation and formic acid dehydrogenation.

New methoxy substituted CNC pincers form ruthenium catalysts that are robust and convert CO2 to CO selectively using light energy.

The phosphine-free "second-generation" Blechert/Hoveyda-Grubbs catalyst Ru(dC(H)C 6 H 4 -o-O-i-Pr)(H 2 IMes)Cl 2 (H 2 IMes ) 4,5-dihydro-1,3-dimesitylimidazol-2-ylidene) and Piers catalyst [Ru(dCHPCy 3 )-(H 2 IMes)Cl 2 ]BF 4 (Cy ) cyclo-C 6 H 11 ) for olefin metathesis effected cross-metathesis (CM) of vinyl chloride and 1,2-dichloroethene with several unhindered terminal and internal alkenes in up to 95% yield (5 mol % catalyst). In most cases, 1,2-dichloroethene was more successful than vinyl chloride. Ring-opening CM of cyclooctene provided greater yields than CM: with vinyl chloride, 93% yield; with 1,2dichloroethene, >95%. Other common Ru-based catalysts failed to effect CM under similar conditions, but instead underwent rapid decomposition. The dimeric ruthenium-monochloromethylidene complex [Ru(dCHCl)(H 2 IMes)Cl(µ-Cl)] 2 was isolated as a thermally unstable intermediate. CM reactions with 1,2-dibromoethene afforded 22% CM product in the best case; halide exchange with the catalyst was significant. CM reactions involving vinyl fluoride typically led to <3 turnovers, but the dimeric intermediate [Ru(dCHF)(H 2 IMes)Cl(µ-Cl)] 2 was sufficiently long-lived to be characterized by single-crystal X-ray diffraction. Ring-opening CM of cyclooctene with vinyl fluoride (55% yield) was more favorable than CM.

The synthesis and optical characterization of 9-(2,6bis(methoxymethyl)phenyl) borafluorene (BMMP-BF) are reported. NMR spectroscopic data and single-crystal X-ray diffraction data of BMMP-BF show intramolecular chelation by the 2,6-bis(methoxymethyl)phenyl moiety via a boron−oxygen dative bond. The optical spectra of BMMP-BF are unusual in that absorption is entirely in the UV region (λ max = 284 nm), yet fluorescence occurs at 536 nm. This equates to a Stokes shift of 2.05 eV (16 500 cm −1 ) and is among the highest Stokes shifts ever reported for a small molecule. Density functional theory (DFT) calculations show that the boron−oxygen dative bond in BMMP-BF is ruptured in the excited state and that emission occurs from a trigonal planar boron geometry. This bond cleavage and the concurrent planarization of the boron center are responsible for the high Stokes shift. Two borafluorenes related to BMMP-BF were also examined: 9-(2,6-bis((methylthio)methyl)phenyl) borafluorene (BMTMP-BF) and 9-(2,6-bis(tert-butoxymethyl)phenyl) borafluorene (B t BuMP-BF). Both BMTMP-BF and B t BuMP-BF have optical properties similar to those of BMMP-BF with remarkably large Stokes shifts. Finally, BMMP-BF-(2T) 2 , which possesses bithiophene moieties on the 2 and 7 positions of a BMMP-BF core, was also synthesized and studied. The absorption spectrum of BMMP-BF-(2T) 2 is red-shifted compared to BMMP-BF. BMMP-BF-(2T) 2 was found to exhibit dual emissions rather than the single, high Stokes shift emission of BMMP-BF. DFT calculations suggest that the dual emissions of BMMP-BF-(2T) 2 arise due to radiative relaxation from two different structures in the excited state.

T h e m e c h a n i s m o f t h e b i s -(trineopentylphosphine)palladium(0) (Pd(PNp 3 ) 2 )-catalyzed coupling of aryl halides and aniline derivatives was studied in an effort to understand the role of substrate steric effects on the reaction. Prior studies had shown that the rate of Pd/ PNp 3 -catalyzed coupling of aryl bromides and aniline derivatives was largely unaffected by substrate steric demand. The oxidative addition of aryl bromides to Pd(PNp 3 ) 2 is found to follow first-order kinetics with a rate that is independent of both ligand and aryl halide concentration. Thus, the rate limiting step for oxidative addition of aryl bromides is irreversible ligand dissociation. In the case of aryl chlorides, the oxidative addition rate has a first-order dependence on [ArCl] and an inverse dependence on [PNp 3 ], indicating a mechanism involving reversible dissociation of the ligand followed by rate limiting oxidative addition. This difference in aryl halide effect was also found for the catalytic coupling reaction. Aryl bromide steric demand does not affect the coupling rate with hindered anilines, whereas the coupling rate of aryl chlorides is negatively affected by substrate steric demand. These results suggest that oxidative addition is rate limiting in the catalytic reaction for aryl chlorides but that oxidative addition is not rate limiting for aryl bromides. Aniline was found to give coupling rates significantly slower than those of 2,6-diisopropylaniline for both aryl bromides and chlorides. Aniline promotes the decomposition of the [(PNp 3 )Pd(Ar)(μ-X)] 2 catalytic intermediate to a catalytically inactive palladacycle ([(κ 2 -P,C-Np 2 PCH 2 C(Me 2 )CH 2 )Pd(μ-X)] 2 ) through C−H activation of a neopentyl group and elimination of arene. These studies show that the ability of the Pd/PNp 3 catalyst system to tolerate steric demand in aryl bromides stems from the fact that the rate limiting step of the catalytic cycle is independent of the concentration and steric demand of aryl bromides. A catalyst deactivation pathway involving ligand metalation was identified that is promoted by unhindered aniline derivatives.