Controlling Proton Delivery Through Catalyst Structural Dynamics

Angewandte Communications Chemie

International Edition:DOI:10.1002/anie.201607460 Homogeneous Catalysis German Edition:DOI:10.1002/ange.201607460 Controlling Proton Delivery through CatalystStructural Dynamics Allan JayP.Cardenas,Bojana Ginovska, Neeraj Kumar,Jianbo Hou, Simone Raugei, Monte L. Helm, Aaron M. Appel, R. Morris Bullock, and Molly OHagan*

Abstract: The fastest synthetic molecular catalysts for H2 structural dynamics in catalysis is demonstrated through the production and oxidation emulate components of the active modulation of catalytic rates over three orders of magnitude site of hydrogenases.The critical role of controlled structural for molecular Ni electrocatalysts for H2 production. This rate dynamics is recognized for many enzymes,including hydro- enhancement is achieved by controlling the structural dynam- genases,but is largely neglected in designing synthetic catalysts. ics involved in key proton-transfer steps. Our results demonstrate the impact of controlling structural Highly active electrocatalysts for the production and Ph C6H4R 2+ R R’ 2+ dynamics on H2 production rates for [Ni(P 2N 2)2] oxidation of H2,such as the [Ni(P 2N 2)2] catalysts R R’ catalysts (R = n-hexyl, n-decyl, n-tetradecyl, n-octadecyl, (P 2N 2 = 1,5-diaza-3,7-diphosphacyclooctane with alkyl or phenyl, or cyclohexyl). The turnover frequencies correlate aryl groups on the Pand Natoms), have been developed by inversely with the rates of chair–boat ring inversion of the incorporating abase in the second coordination sphere of the ligand, since this dynamic process governs protonation at metal to act as aproton relay (Scheme 1), asystem similar to either catalytically productive or non-productive sites.These the active site of the [FeFe]-hydrogenase.[6] Thereactivity of results demonstrate that the dynamic processes involved in proton delivery can be controlled through modification of the outer coordination sphere,inamanner similar to the role of the protein architecture in many enzymes.Asadesign parameter, controlling structural dynamics can increase H2 production rates by three orders of magnitude with aminimal increase in overpotential.

The high catalytic efficiency of metalloenzymes is attributed to the active-site structure and control of the active-site Ph C6H4R 2+ Scheme 1. Structure of the nickel(II) complexes: [Ni(P 2N 2)2] . environment, including the precise regulation of substrate Forcomplex characterization, including X-ray structures, see the the delivery and product removal. This regulation is achieved SupportingInformation. through the extended architecture of the protein, interaction with the medium, and controlled structural dynamics,which can dictate active-site access as well as precise positioning of these modular catalysts can be controlled through systematic active components throughout the catalytic reaction.[1] The changes in the steric and electronic characteristics of the structural dynamics of molecular catalysts can also have ligands and the basicity of the pendant amine.[7] Changes to aprofound effect on catalytic performance.Dynamics has the medium composition have substantial effects on the been used as adesign feature to modulate chemoselectivity reactivity of these complexes,with significant rate enhance- [2] [3] and enantioselectivity, to enhance electron transfer, to ments observed in protic ionic liquid/H2Omedia compared to determine enantiomeric excess,[4] and even to turn the activity traditional organic solvents.[8] Proton mobility in these media of the catalyst on or off.[5] However,predicting and control- is critical for fast catalysis,but proton mobility alone does not ling the effects that ligand dynamic processes can have on account for the observed rate enhancement, especially for 1- reactivity is challenging when designing new catalytic systems, C6.[8b] We have now identified the source of the dramatic rate whether synthetic molecular systems or within aprotein enhancement as modulation of the ligand dynamics that framework. In this study,the importance of controlling control the positioning of the pendant amine,and therefore the protonation site.Weobserved aremarkable correlation [*] Dr.A.J.P.Cardenas, B. Ginovska, Dr.N.Kumar,Dr. J. Hou, between ligand structural dynamics and catalytic perfor- Dr.S.Raugei, Dr.M.L.Helm, Dr.A.M.Appel, Dr.R.M.Bullock, mance,which is controlled through different substituents on Dr.M.O’Hagan the periphery of the ligand, seven bonds away from the metal Center for Molecular Electrocatalysis (Scheme 1). Controlling the ligand dynamics led to an Pacific Northwest NationalLaboratory increase in the catalytic activity by more than three orders P.O. Box 999, K2-57, Richland,WA99352 (USA) of magnitude in acetonitrile/water solution, giving H2 pro- E-mail:[email protected] 6 1 duction turnover frequencies of 1.5 10 sÀ .Bycombining Dr.A.J.P.Cardenas Current address:221 Science Center catalyst modification and the use of protic ionic liquids,we 7 1 State University of New York at Fredonia achieved catalytic rates up to 4.5 10 sÀ ,which, to our Fredonia, NY 14063 (USA) knowledge,isthe fastest catalysis for this transformation to Supportinginformation for this article can be found under: date. http://dx.doi.org/10.1002/anie.201607460.

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To rapidly reduce protons,the six-membered ring con- In many natural catalysts,the outer coordination sphere taining the pendant amine and the metal center of [Ni- modulates dynamic processes essential to catalysis through R R’ 2+ [1] (P 2N 2)2] systems must adopt aboat conformation complex intramolecular and solvent interactions. To emu- (Scheme 2), with the lone pair of the amine oriented endo late this control in amolecular system that is more syntheti- cally accessible,substituents of varying size and structure were incorporated into the outer coordination sphere of the catalyst (Scheme 1) to modulate interconversion of the boat and chair conformers.The boat–chair isomerization rates for Ph C6H4R 2+ the [Ni(P 2N 2)2] series of catalysts were measured by lineshape analysis of the variable-temperature 31P{1H} NMR II spectra for the Ni complexes in CD2Cl2/CD3CN as the solvent to provide the required low-temperature range for Eyring analysis.[11] TheNiII complexes have atrigonal bipyramidal structure in which acetonitrile is the fifth ligand. The presence of this fifth ligand results in two different phospho- rus environments in the trigonal bipyramidal structure,which interconvert through dissociation of the acetonitrile,chair– boat isomerization, and re-coordination of acetonitrile.[11] Details of the exchange process,representative spectra, and Eyring analyses are shown in the Supporting Information. As the length of the n-alkyl chain of the substituent in the outer coordination sphere is increased, the rate of chair–boat isomerization decreases,and the turnover frequency (TOF) Scheme 2. Branching of the catalytic cycle occurs due to protonation increases up to three orders of magnitude,asshown in at the inactive exo site or active endo site. Only endo protonation Ph C6H4R 2+ Figure 1. The[Ni(P 2N 2)2] complexes catalyze H2 results in H2 formation (top pathway). The exo protonation is stabilized by boat-to-chairisomerization of the ligand to form ahydro- gen bond (bottom pathway), thereby resulting in aconformer that is thermodynamically and kinetically stabilized to the deprotonation required to resume catalytic activity.

with respect to the metal center. Protonation of the chair conformer, which is often the kinetically preferred protonation site,positions protons exo to the metal center,where they

cannot interact with the metal center.Toproduce H2,these exo-protonated species require isomerization through deprotonation of the exo position followed by protonation in the endo position. This isomerization process is slow relative to electrocatalysis,and leads to accumulation of the exo- Figure 1. Correlation between catalytic rates of H production mea- protonated species in the electrochemical diffusion layer, 2 sured in protonated dibutyl formamidebis(trifluoromethanesulfonyl)a- effectively attenuating the concentration of the active catalyst mide/water ([(DBF)H]NTf /H O) and boat–chairisomerization rates [7a,9] 2 2 and thereby decreasing the observed rates of catalysis. Ph C6H4R 2+ measured in 4:1CD2Cl2/CD3CN for the [Ni(P 2N 2)2] series. Thestability of the exo-protonated isomers is increased by intramolecular N H···N hydrogen bonding,that is,the “exo À pinch”, which stabilizes the protonation site by more than production, and the plateau of the scan-rate-independent [10] 5pKa units relative to the non-pinched isomer. Thekinetic electrocatalytic current was used to determine the catalytic stability of the protonation site is also increased by the rate,orTOF,inthe media indicated in Table 1byusing presence of the hydrogen-bonding interaction, where access established methods.[12] Foreach catalyst, the catalytic current

to the exo-pinched proton by the external base is hindered by (icat)exhibited first-order dependence on catalyst concentra- the second amine.Avoiding the formation of the N H···N tion and plateaued to the steady-state value as the scan rate, À hydrogen bond would greatly accelerate the exo–endo acid concentration, and water content increased (Figures S4– isomerization process and therefore the rate of catalysis. S9 in the Supporting Information). Astrong linear correlation Theformation of the exo-pinched species could be limited by is observed between the log(TOF) vs.log(boat–chair isomer- slowing the boat–chair isomerization that leads to the pinched ization rate) values for the seven complexes of the series in species,asillustrated in Scheme 2. To test this hypothesis,we three media, which is consistent with the dependence of the synthesized aseries of catalyst derivatives with various TOFonthe boat–chair isomerization rates.Complexes 2 and substituents in the outer coordination sphere,and measured 3 exhibit TOFs that fit the linear correlation. Notably,the the impact of slowed structural dynamics on catalytic TOFdoes not correlate with the structure of the outer- performance. coordination-sphere substituents or the driving force for

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Ph C6H4R 2+ Table 1: Boat–chair isomerization rates, turnover frequencies, and overpotentials of the [Ni(P 2N 2)2] series.

MeCN MeCN [(DBF)H]NTf2/H2O Ph C6H4R 2+ [Ni(P 2N 2)2] Boat–chair Dry Wet cH2 O =0.68–0.71 isomerization rates (0.8–1.1 m H2O) [a] k298K TOF h TOF h TOF h 1 1 1 1 [sÀ ][sÀ ][mV] [sÀ ][mV] [sÀ ][mV] 1 7.0 106 590 400 720 400 6.0 104 420 1-C6 2.4 106 200 340 740 400 6.0 105 410 1-C10 1.5 106 740 310 3400 420 4.0 106 440 1-C14 8.7 105 2900 320 9.8 104 440 2.0 107 520 1-C18 7.5 105 2.9 104 330 1.5 106 470 4.5 107[b] 570 2 3.7 106 690 330 4000 440 1.8 105 430 3 1.7 106 400 370 1500 470 2.5 106 500

[a] Boat–chairisomerization rates measured in 4:1CD2Cl2 :CD3CN. With the addition of water,upto0.5 m,nochange in the boat–chair isomerization rates were observed compared to dry solvents. [b] Due to limited solubility in [(DBF)H]NTf2/H2O, the diffusion coefficients for 1-C18 could not be measured.Therefore, the TOF of 1-C18 was estimated using the Dcat measured for 1-C14.

[8b] protonation and H2 formation, that is,the basicity of the indicating that this medium affords rapid proton movement pendant amine and metal center.[7a] and possibly further attenuation of the structural dynamics R R’ 2+ [14] Recent kinetic analysis of [Ni(P 2N 2)2] systems iden- due to solvent effects such as viscosity, hydrophobicity,or tifies proton transfer,that is,protonation/deprotonation, as ion pairing (Table S5). alimiting factor for catalysis,and illustrates that the addition In addition to slowing ligand structural dynamics,the long of water reduces these barriers,thereby increasing catalytic alkyl chain may facilitate fast rates by sterically blocking the rates.[13] In comparing the alkyl series 1-C6 through 1-C18, exo protonation site through hydrophobic packing, either aTOF increase of 150-fold is observed in dry MeCN as the intra- or intermolecularly.Asshown in the crystal structures boat–chair isomerization rate is decreased by afactor of nine. of the Ni0 complexes (Figure S16), the alkyl chains of the Ni0 In MeCN with added water, a2000-fold faster rate is observed complex 1-C14,that is, 1-C14a,dostack intermolecularly in for 1-C18 compared to 1-C6,with no additional change in an extended structure,with similar structural motifs observed boat–chair isomerization rate (Figure 2). These data suggest for both 1-C10a and 1-C6a.Such intermolecular aggregation that in dry acetonitrile,protonation/deprotonation is com- has been hypothesized to enhance catalytic rates in molecular petitive with boat–chair isomerization for the rate-determin- catalysts such as the iridium water-oxidation catalysts ing step(s), but not when water is added to facilitate proton reported by Macchioni and co-workers.[15] In the case of the transfer. If proton delivery or removal is no longer rate- 1-Cn series reported here,increasing the alkyl chain length limiting, the boat–chair inversion process controls catalysis by does not substantially affect the diffusion coefficients attenuating the formation of the catalytically incompetent (Table S1). Thedifference between the diffusion coefficients exo-pinched isomer.[9] Adetailed mechanistic understanding of these catalysts and other catalysts with para substituents, of this system has guided catalyst design and medium such as Br or OMe,[8b] is small and may be accounted for by selection to control proton delivery and thereby attain fast their increased size.The relative diffusion coefficients are not rates.Further rate enhancement for this series,upto4.5 consistent with aggregation of the catalysts in solution. 7 1 10 sÀ ,isobserved in [(DBF)H]NTf2/H2O(Figure 2), thus Furthermore,the diffusion coefficients are not concentration

Figure 2. a) Cyclic voltammogramof10mm 1-C14 in acetonitrile (MeCN;blue);and MeCN with 1.1m water (MeCN/H2O; red);with 0.2m + Bu4NBF4 supporting electrolyte and using 600 mm protonated dimethylformamide [(DMF)H ]asthe acid. The black trace is the cyclic 1 À voltammogramof10mm 1-C14 in [(DBF)H]NTf2/H2O, cH2 O =0.68. Conditions:scan rate of 0.2 Vs ,1mm glassy carbon working electrode, +/0 Ph C6H4R 2+ potentials referenced to Cp2Fe (0 V). b) Comparison of TOF for the [Ni(P 2N 2)2] series in three media listed in (a).

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dependent (Table S6), and the catalytic current shows first- open coordination site is necessary for accepting/delivering order dependence on catalyst concentration (Figure S7). protons,and this is achieved through interactions with the These findings are not consistent with the rate of enhance- outer coordination sphere.[6b] Extensive control of the ligand Ph C6H4R 2+ ment being the result of oligomerization. Modulation of the structural dynamics in the [Ni(P 2N 2)2] system can be structural dynamics by intramolecular interactions,aswell as attained through modifications to the outer coordination the potential impact of solvent upon intramolecular inter- sphere that result in mesoscale medium effects.Byincluding actions,was investigated computationally and is discussed in control of ligand structural dynamics as adesign feature of

the Supporting Information. molecular catalysts,the rates of H2 production by the Ph C6H4R 2+ TheTOF increases up to three orders of magnitude while [Ni(P 2N 2)2] system are enhanced by three orders of the rate of isomerization decreases by approximately one magnitude without asignificant loss in energy efficiency.The ° order of magnitude,that is,anincrease in DG isomerization of remarkable rate enhancements observed in the 1 ° Ph C6H4R 2+ 1.4 kcalmolÀ .Alarger change in DG would be expected [Ni(P 2N 2)2] system as afunction of controlled struc- given that the barrier is proposed to be the key contributor to tural dynamics illustrate how this new design parameter can the change in the catalytic rates.However,the barrier for the be used to obtain catalytic performance that rivals that of isomerization process could only be measured for the NiII enzymes. complexes as amodel for the reduced nickel complexes that are protonated during catalysis.The trend measured for the NiII series,that is,decreasing isomerization rates with Acknowledgements increased substituent size,isexpected to be maintained for all oxidation states of the metal center[11] and medium This research was supported as part of the Center for compositions (Table S5). Moreover,the effect that the Molecular Electrocatalysis,anEnergy Frontier Research change in isomerization barrier has on the catalytic rate is Center funded by the U.S. Department of Energy,Office of expected to be compounded by the presence of two required Science,Office of Basic Energy Sciences,and was performed

proton transfers for the production of H2,both of which are in part using the Molecular Science Computing Facility in the complicated by multiple possible protonation sites.[9] William R. Wiley Environmental Molecular Sciences Labo- Thelarge increase in TOFobserved for these systems is ratory,aDOE national scientific user facility located at the not accompanied by asubstantial increase in overpotential Pacific Northwest National Laboratory (PNNL). PNNL is (Figure 3). Theoverpotential was experimentally determined operated by Battelle for DOE.

Keywords: artificial enzymes ·electrocatalysis · homogeneous catalysis ·hydrogen production · structural dynamics

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