Optimal functionalization of a molecularelectrocatalyst for hydride transferShenzhen Xua and Emily A. Carterb,c,d,1

aDepartment of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544-5263; bSchool of Engineering and Applied Science,Princeton University, Princeton, NJ 08544-5263; cOffice of the Chancellor, University of California, Los Angeles, CA 90095-1405; and dDepartment ofChemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095-1592

Contributed by Emily A. Carter, September 19, 2019 (sent for review July 15, 2019; reviewed by Victor S. Batista and Clark Landis)

Optimization of hydride transfer (HT) catalysts to enhance rates andselectivities of (photo)electroreduction reactions could be a crucialcomponent of a sustainable chemical industry. Here, we analyzehow ring functionalization of the adsorbed transient intermediate2-pyridinide (2-PyH−*)—predicted to form in situ from pyridine (Py)in acidified water at a cathode surface and to be the key to selectiveCO2 photoelectroreduction on p-GaP—may enhance catalytic activ-ity. Earlier studies revealed that 2-PyH−*’s instability results from aprotonation side reaction producing adsorbed dihydropyridine(DHP*), which is relatively HT-inactive. Reducing the electron den-sity on 2-PyH−* could limit this protonation, with the trade-off thatit may become less active for HT from 2-PyH−*–R to CO2. We explorehere how Py functionalization affects the electron distribution andin turn tunes the catalytic performance of 2-PyH−*. We indeed findthat electron-withdrawing groups could enhance the stability of2-PyH−* by reducing its electron density on the ring. Furthermore,we find that the change in the number of electrons on the substitutinggroup of the hydride donor is a good descriptor for both the stabilityagainst protonation and the magnitude of the HT barrier. Wepredict that –CH2–CH2F is the best candidate substituent, as itsignificantly improves the stability of 2-PyH−* with only asmall increase in HT barrier. –CH=CH2 and –CH2F also could bepromising, although they require further investigation due to alarger HT-barrier increase.

catalyst functionalization | hydride transfer | carbon dioxide reduction

Acommon path of reduction reactions is the transfer of ahydride ion, with its pair of electrons, from a reductant to an

oxidant. This hydride transfer (HT) process plays an importantrole in energy conversion systems, e.g., hydrogen evolution re-actions (1, 2) and CO2 reduction reactions (CO2RRs) (3, 4) in(photo)electrochemical cells. In 2008, the Bocarsly group con-ducted an experiment for CO2 photoelectrochemical reductionon GaP electrodes (5), where CO2 was selectively reducedto CH3OH with a high faradaic efficiency (∼100%) at 0.3 Vunderpotential in the presence of pyridine (Py) in aqueous so-lution at pH 5.2. Here, 0.3 V underpotential means that theapplied potential is 0.3 V less negative than the standard re-duction potential for converting CO2 to CH3OH. By systematicprocess of elimination, subsequent theoretical work from theCarter group (6–10) suggested that the molecular adsorbate 2-pyridinide (2-PyH−*; * indicates an adsorbed species) is the mostlikely catalytic intermediate for the heterogeneous CO2RR onGaP surfaces, which is preferentially formed via the reaction Py* +H+ + 2e− → 2-PyH−*. The catalytic effect of this hydride donor,which is induced by the de-aromatization of the Py ring, is di-rectly analogous to that observed in the reduction of carboxylicesters and carboxamides catalyzed by de-aromatized Py ligands(formed by hydride addition) in transition metal complexes (11,12). Mechanistic studies (9, 10) conducted by the Carter grouprevealed that the experimental system’s catalytic performance islimited by 2-PyH−*’s instability in an acidic environment. Astrong driving force exists for 2-PyH−* to be protonated to formadsorbed dihydropyridine (DHP*), which is relatively HT inactive.

The reaction 2-PyH−* + H+sol → DHP* is estimated to be exer-

gonic by 0.44 eV at pH 5.2 (10). Here, “stability” specifically refersto the hydride donor’s inertness to side reactions with positivelycharged species.Developing an approach to tune the electron density on the

molecular catalyst 2-PyH−* could help improve the catalytic per-formance of 2-PyH−*, as shown by the Carter group’s previousstudy (13), where a surface doping strategy was proposed tooffer modest enhancement. In the present work, we explorethe effect of Py functionalization on the system’s catalyticperformance. We employ a solvated embedded cluster modelto calculate protonation free energies and barriers to HT toCO2 for 2-PyH

−* with a variety of substituents. We tested electron-withdrawing groups that could reduce the electron density on the2-PyH−* adsorbate, in order to make protonation less exergonic(Fig. 1). Balancing the 2 competing reactions (protonationvs. HT) could yield the optimal substituent to accelerate theCO2RR.

Results and DiscussionWe first consider potential positions for the substituent and thehydride on the ring molecule Py [2-PyH−* was predicted to formfrom Py* (7, 8)]. There are 13 unique configurations of an R-substituted 2-PyH− molecule (2-PyH−

–R; here, “R” refers to asubstituent), considering all possible positions of the –R groupand the hydride on the Py molecule (Scheme 1A). We calculated

Significance

Catalytic reduction reactions via hydride transfer (HT) areubiquitous in (photo)electrochemical systems being exploredfor sustainable production of fuels and chemicals. Optimizingthe hydride donor—the key catalytic intermediate—is essentialto improving performance. Using a well-vetted density func-tional theory (DFT)-based solvated embedded cluster model,we find that molecular functionalization could significantlyenhance the stability (against protonation) of adsorbed 2-pyridinide,which is the probable hydride donor in heterogeneous CO2

reduction to methanol on GaP photoelectrodes. Specifically,the hydride donor’s performance correlates strongly with theelectron-withdrawing capability of substituents. Among all thoseconsidered, the –CH2–CH2F functional group appears to be theoptimal substituent, which is determined by balancing the trade-off between stability enhancement and HT-barrier increase offunctionalized hydride donors.

Author contributions: S.X. and E.A.C. designed research; S.X. performed research; S.X. andE.A.C. analyzed data; and S.X. and E.A.C. wrote the paper.

Reviewers: V.S.B., Yale University; and C.L., University of Wisconsin–Madison.

The authors declare no competing interest.

Published under the PNAS license.1To whom correspondence may be addressed. Email: eac@ucla.edu.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1911948116/-/DCSupplemental.

First published October 28, 2019.

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the energies of these 13 possible configurations for the followingtest cases: 2-PyH−

–COOH, 2-PyH−–CHO, 2-PyH−

–CF3, and2-PyH−

–CN (SI Appendix, Table S1). We find that the –R groupsprefer to substitute for the H atom at the meta position (Scheme1B). Once the –R group is at the meta position, then the hydrideprefers to bind to either of the 2 ortho C atoms or the para Catom, rather than the meta C atoms. The Carter group’s earlierwork (10) showed that HT steps in CO2 reduction to CH3OH arefacilitated by adsorption of intermediates at surface Ga sites. Wetherefore excluded from consideration hydride in the para po-sition because of the long distance for HT from the para positionto an adsorbed hydride acceptor (e.g., CO2 reduction interme-diates HCOOH* or CHO*; ref. 10 and Scheme 1C). We alsodiscarded from consideration hydride binding in the ortho posi-tion adjacent to the –R group, on the basis that steric repulsionbetween the –R group and the hydride acceptor (CO2 mol-ecules or other CO2 reduction intermediates) might inhibitthe latter’s adsorption (Scheme 1D). Therefore, for consis-tency and simplicity in screening Py functional group candi-dates, we only considered 2-PyH−*–R with –R at the metaposition and hydride at the ortho position opposite to the –Rgroup (Scheme 1B).We studied –COOH, –CHO, –CN, –CF3, –CH2F, –CH2OH,

–CH=CH2, and –CH2–CH2F substitutions at the meta site, aspotential electron-withdrawing groups from 2-PyH−*. We alsotested 2-PyH−*–F and 2-PyH−*–Cl and found that thesespecies are not stable on the surface, as they spontaneouslyreact with adsorbed water, H2O*. The most stable configurationof 2-PyH−*–F/Cl is when both the –F/Cl group and the hydridespecies bind to the same C atom. The decomposition reaction is2-PyH−*–F + H2O* → Py* + HFsol + OH−* (using the –F caseas an example). We therefore did not consider such groups thatcould readily form solvated anions by extracting an electron from2-PyH−* (e.g., –halogens or –OH).With knowledge of the preferred atomic configurations for the

functionalized catalytic molecule 2-PyH−*, we then employeda well-vetted density functional theory (DFT)-based solvated

embedded cluster model (14, 15) to calculate the protonationfree energies for 2-PyH−*–R (see Methodology for further cal-culation details). Fig. 2A displays the atomic geometries of thesolvated embedded cluster models used for protonation free-energy calculations. The surface studied here is GaP(110),which is the most active facet, as shown by Hu (16). The pro-tonation reaction is 2-PyH−*–R + H+ (pH 5.2) → DHP*–R, forwhich we obtain the free energies of 2-PyH−*–R and DHP*–Rusing the solvated embedded cluster model and an empiricalvalue (17, 18) for the free energy of dissolved H+ at pH 5.2(discussed in Methodology).We discovered a good reaction descriptor that correlates lin-

early with the protonation free energies of all 2-PyH−*–R con-sidered here (Fig. 3A). The descriptor (on the horizontal axis) isdefined as ΔN = N(atoms of –R in 2-PyH−

–R) − N(atoms of –Rin an isolated gas-phase state), where N is the number of elec-trons extracted from Bader charge analysis (19, 20). The de-scriptor ΔN is the change in the number of electrons on –R whenit substitutes for a hydrogen atom (at the meta position) in anisolated gas-phase 2-PyH− molecule, which is easily obtained by2 inexpensive molecular DFT calculations. The protonation freeenergy (at pH 5.2) of unfunctionalized 2-PyH−* shown in Fig. 3Awas reported in earlier work (10). The linear correlation in Fig.3A can be explained as follows: A larger ΔN for a given –Rmeans that this –R group draws more electron density from the2-PyH− molecule, producing a less basic molecule and a lessnucleophilic hydride donor. The 2-PyH−*–R protonation re-action thus will be less exergonic (see vertical axis in Fig. 3A),resulting in a more stable 2-PyH−*–R.Another important factor for the catalytic performance of

2-PyH−*–R is the hydride-donating ability, which is determined bythe barriers for HT from 2-PyH−*–R to CO2. Although the sta-bility against protonation of 2-PyH−*–R is improved by electron-withdrawing groups, this functionalization may slow down HT dueto the electron density reduction on 2-PyH−*, rendering the latterless negatively charged and hence less hydridic. We calculatedbarriers for HT from 2-PyH−*–R to CO2 again using a solvatedembedded cluster model (see Methodology and the structureshown in Fig. 2B). Predicted HT barriers are plotted against thedescriptor ΔN in Fig. 3B. As found for the protonation free en-ergies, a good linear correlation exists between the HT barrier andΔN. 2-PyH−*–R with a larger ΔN generally has a higher HTbarrier because reduced electron density on the hydride donorreduces its hydride-donating ability. The free-energy diagram andinitial-state (IS)/transition-state (TS)/final-state (FS) atomicstructures for HT for a representative case (2-PyH−*–COOH) areshown in SI Appendix, section S2.The results in Fig. 3 make clear that withdrawing electron

density from the hydride donor improves its stability againstprotonation but may slow down HT. Fig. 4 summarizes thesefindings by displaying the relationship between the protonationfree energies and the HT barriers. We see directly that the HTbarrier increases as the protonation free energy becomes lessnegative. Balancing these 2 competing reactions (protonation vs.HT) guides the search for optimal substituents. The overall HTrate from the adsorbed hydride donor is RHT ∝ exp(Ep/kBT)/[1 +exp(Ep/kBT)] × exp(−Eb/kBT), where Ep and Eb are the pro-tonation free energy and HT barrier, respectively. The first termexp(Ep/kBT)/[1 + exp(Ep/kBT)] is the fraction of adsorption sitesoccupied by 2-PyH−*–R (competing with DHP*–R), i.e., thecoverage of the hydride donor on the electrode surface. Thesecond term exp(−Eb/kBT) is proportional to the HT rate forthat hydride donor. From the expression of the overall HT rateRHT, the system’s catalytic performance could be improved ifRHT(2-PyH

−*–R) is larger than RHT(2-PyH−*) (corresponding

to the green shaded region in Fig. 4). The upper boundary of thegreen shaded region is determined by imposing the conditionRHT(2-PyH

−*–R) = RHT(2-PyH−*), to not degrade HT kinetics

Fig. 1. Schematic illustration of manipulating the charge on the hydridedonor 2-PyH−* via a functionalization approach. The functional group –Rcould withdraw electron density from the 2-PyH−* (blue thick arrow) andhinder the protonation side reaction (red dashed arrow).

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while improving stability against protonation. Based on the ex-pression for RHT, we have the following:

eEp ð2-PyH−*-RÞ

kBT

1+ eEpð2-PyH−*-RÞ

kBT

× e−Ebð2-PyH−*-RÞ

kBT =eEpð2-PyH−*Þ

kBT

1+ eEp ð2-PyH−*Þ

kBT

× e−Ebð2-PyH−*Þ

kBT , [1]

where Ep(2-PyH−*) = −0.44 eV (10), Eb(2-PyH

−*) = 0.33 eV (8).Given that kBT = 0.0257 eV, eEpð2−PyH−*Þ=kBT = e−0.44÷0.0257= 3.7 ×10−8, thus ½1+ eEpð2−PyH−*Þ=kBT � can be approximated safely as 1.Then we have the following:

Eb

�2-PyH−*-R

�=Ep

�2-PyH−*-R

�+ 0.44 eV− kBT

× ln

0@1+ e

Epð2-PyH−*-RÞkBT

1A+ 0.33 eV.

[2]

Eq. 2 gives an expression for Eb(2-PyH−*–R) as a function of

Ep(2-PyH−*–R), which corresponds to the expression used to plot

the upper boundary of the green shaded region in Fig. 4. For theprotonation free energy, we only need to consider the range of Epfrom −0.44 to 0.06 eV at pH 5.2. A more positive protonationfree energy (Ep > 0.06 eV) is not necessary, as the active siteson the surface for hydride donor adsorption will be saturatedwith 2-PyH−*–R (replacing DHP*–R with 90% occupancy of2-PyH−*–R). This is why the green shaded region in Fig. 4 onlycovers the protonation free energy from −0.44 eV (the referencevalue for the unsubstituted 2-PyH−*) to 0.06 eV.The data points of 2-PyH−*–CH2F, 2-PyH

−*–CH=CH2, and2-PyH−*–CH2–CH2F fall within the green shaded region of Fig.4. The distance of the 2-PyH−*–CH2–CH2F data point to theupper boundary of the green region is the largest (+0.27 eV),

indicating that –CH2–CH2F is the optimal functional groupamong those studied for improving the performance of the cat-alytic intermediate 2-PyH−*. The distances of the 2-PyH−*–CH2Fpoint and the 2-PyH−*–CH=CH2 point to the upper boundary ofthe green region are only +0.02 and +0.11 eV, within expecteduncertainties of DFT approximations and our cluster model. Al-though –CH2F and –CH=CH2 substituents are less promisingcompared to –CH2–CH2F, these 2 candidates might be worthinvestigating experimentally as well.Now that we identified 3 potentially improved molecular

electrocatalysts, it is critical to ensure that these substituted in-termediates actually can form at the electrode interface. Thereaction for 2-PyH−*–R formation is Py*–R + H+ + 2e− →2-PyH−*–R. Relevant metrics include the functionalized Py bind-ing energy (to ensure it will adsorb on the electrode prior toreduction) and the reduction potential (the thermodynamicdriving force) to form the anionic catalyst. Predicted adsorptionfree energies of Py*–CH2F, Py*–CH=CH2, and Py*–CH2–CH2Fare −0.42, −0.5, and −0.38 eV, respectively (see Methodology fordetails). The predicted adsorption free energy of unsubstitutedPy* is −0.28 eV (15). Thus, adsorption of Py* with any of the 3promising –R groups is more favorable than for unsubstitutedPy*, indicating a higher surface coverage for Py*–R (–CH2F,–CH=CH2, and –CH2–CH2F). Using the reduction potential forunsubstituted 2-PyH−* formation (−1.09 V vs. SCE at pH 5.2) asa reference (8), we predict that the reduction potentials for2-PyH−*–CH2F, 2-PyH

−*–CH=CH2, and 2-PyH−*–CH2–CH2Fformation are each less negative than that of the unsubstituted2-PyH−* by ∼0.11 V. This suggests that formation of 2-PyH−*–CH2F,2-PyH−*–CH=CH2, or 2-PyH

−*–CH2–CH2F is more favorable thanunsubstituted 2-PyH−*, which should further improve the electro-catalytic activity of this molecularly functionalized semiconductorelectrode.

A B

C D

Scheme 1. Potential positions on the Py ring for the substituent and hydride. (A) Two ortho, 2 meta, and 1 para positions in Py are possiblesubstitutional positions for the functional group –R and possible binding sites for hydride H−. (B) Structure of a functionalized hydride donor2-PyH−

–R (here, –COOH), where –R is at the meta position and hydride is at the ortho position opposite to the –R group. (C ) Schematic config-uration of hydride at the para position, which was not considered due to the relatively long distance of the HT path (depicted by the blue arrow) toany adsorbed CO2 reduction intermediate [e.g., HCOOH* or CHO* (10)]. (D) Schematic configuration of hydride at the ortho position adjacent tothe –R group, which was not considered due to anticipated steric repulsion between the –R functional group and the adsorbed CO2 reductionintermediate.

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In closing, the overall good correlations (demonstrated by theR2) shown in Fig. 3 indicate that ΔN should be a reliable descriptorfor estimating protonation-free-energy/HT-barrier changes offunctionalized hydride donors. Although ΔN cannot directly offer aprecise value corresponding to an optimal substituent for a hydridedonor, we were able to identify a reasonable range of ΔN thatproduces sufficient decreases in protonation exoergicities withoutinducing kinetically forbidden barriers (green region in Fig. 4). Thispredicted range of the descriptor can help exclude other substitu-ents with too large ΔN, which could significantly reduce searchcosts. The descriptor ΔN therefore could be a useful guide for HTcatalyst design.

ConclusionsMolecular functionalization offers a strategy to improve the cata-lytic performance of a molecular hydride donor, via balancing thetrade-off between its stability against protonation and its HT bar-rier. Reducing the electron density on the hydride donor by func-tionalization with an electron-withdrawing group could improve thestability of the hydride donor but also could slow down HT. Wetested these concepts via a well-vetted cluster model for hetero-geneous CO2 reduction on GaP(110) surface cocatalyzed by thepostulated hydride donor 2-PyH−*. A variety of functional groupswere tested for their influence on the stability and HT barrier of2-PyH−*–R. The number of electrons that a functional groupwithdraws from the 2-PyH−molecule (ΔN as defined in Results andDiscussion) is a good descriptor for the changes in protonation freeenergy and HT barrier in a wide variety of 2-PyH−*–R cases. Thequalitative trend is that a substituent with a larger ΔN (strongerelectron-withdrawing effect) leads to a less negative protonationfree energy (better stability) and a higher HT barrier (slower HT).

Hence, there exists a trade-off between better stability and worseHT kinetics when searching for the optimal functional group. Thecorrelation of the hydride donor’s stability and hydride-donatingcapability with the electron-withdrawing tendency (described byΔN) of the substituents provides insights and guidance for futuredesign of other types of molecular hydride donors for use in HTcatalysis. For the specific case of heterogeneous CO2 reduction ona GaP electrode with the cocatalyst Py, the –CH2–CH2F functionalgroup emerged as the most promising candidate with a significantdecrease in the protonation exoergicity and a relatively small in-crease in the HT barrier, indicating an opportunity to improve theoverall catalytic performance of this system.

MethodologyWe used the ORCA program, version 3.0.3 (21), to carry out DFT calculationswith the B3LYP hybrid exchange-correlation (XC) functional (22–24). Ge-ometry optimizations were performed with Pople 6-31G** all-electron basissets (25, 26) for all non-Ga atoms. The Stuttgart effective core potential (ECP)and corresponding valence double-ζ basis set were used to describe the 3valence electrons of each Ga atom (27, 28). Subsequent single-point energycalculations to refine the total energies made use of all-electron aug-cc-pVDZ basis sets (29, 30) for all non-Ga atoms, while the Ga ECP/basisremained the same. The self-consistent field (SCF) and geometry optimiza-tion convergence criteria were set to 10−8 hartree (2.72 × 10−7 eV) and 5 ×10−6 hartree (1.36 × 10−4 eV), respectively, for the system’s total electronicenergy. We employed the default integration grid in the ORCA package forDFT calculations. For SCF iterations, the angular and radial grid schemesselected were Lebedev-110 (31–34) and Gauss–Chebyshev (35, 36) (with anaccuracy parameter IntAcc = 4.34), respectively. For the final energy evalu-ation, Lebedev-302 and Gauss–Chebyshev (with an accuracy parameterIntAcc = 4.67) were employed. The parameter IntAcc determines the numberof radial points for a given atom, nrad(A) = 5×(3×IntAcc + nA − 8), where nA isthe row of the periodic table of element A. The integrated number of

A

B

Fig. 2. Atomic geometries of the solvated embedded cluster model used for calculating (A) the reaction free energy for protonation of 2-PyH−*–R (–COOHshown here as a representative case), where the Left and Right correspond to the reactant and product state, and (B) the HT barrier for 2-PyH−*–R, where theblue arrow depicts the HT direction, pointing from the hydride moiety in 2-PyH−*–R to the carbon atom in CO2. For the cluster model in A, the protonatingproton (H+

sol) was not included explicitly; instead, an empirical value (17, 18) was assigned for the free energy of H+sol.

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electrons in the system can be used to verify sufficient density of the in-tegration grid. A representative case of 2-PyH−*–CH2CH2F shows that theintegrated number of spin-up/down electrons equals 304.9991/304.9991,close to the actual value of 305, which verifies that the default setting ofORCA is sufficient for our system. The full input files for our geometry op-timization and single-point energy calculations are provided at the end of SIAppendix. All of the species considered here are closed shell; hence theoverall spin was restricted to zero throughout. We applied Grimme’s aposteriori, semiempirical D2 dispersion correction (37) to capture lateral in-teractions between adsorbates more accurately in all of the calculations.

We used the mixed implicit–explicit solvation scheme, validated in theCarter group’s previous work (15, 38), to include solvation effects. This ap-proach uses the implicit Solvation Model based on solute electron Density(SMD) (39) in the presence of a full monolayer of half-dissociated watermolecules adsorbed on the cluster’s surface. A previous theoretical–experi-mental characterization of the GaP(110)/water interface showed that thisadsorbed half-dissociated water monolayer is the most thermodynamicallystable configuration (40, 41).

We employed this solvated cluster model to compute the protonation freeenergies and the HT barriers of 2-PyH−* with different substituents. Thesolvated cluster contains 24 Ga atoms, 24 P atoms, and 40 H atoms passiv-ating the dangling bonds at the nonsurface edges of the cluster. This em-bedded cluster model was validated in the Carter group’s earlier work (14).Fig. 2 shows the atomic structures of the cluster models used for protonationfree-energy and HT-barrier calculations.

For the free energy of H+sol (pH 5.2), we have G(H+

sol; pH 5.2) = G(H+sol;

pH 0) – 5.2 × 0.059 eV, where G(H+sol; pH 0) is the free energy of H+

sol at anaqueous standard condition (1 M of H+ in aqueous solution). We use an

empirical value from the literature of −11.73 eV for G(H+sol; pH 0) (17, 18).

Hence, G(H+sol; pH 5.2) = −12.04 eV.

For the HT-barrier study, frequency calculations were performed to con-firm that the optimized structures of ISs and FSs are local minima and thatonly a single imaginary mode is present in TS structures. We optimized TSstructures using the eigenvector-following method implemented in ORCA.We first applied the dragmethod to scan the potential energy surface along apostulated reaction pathway starting from a fully relaxed IS. The reactionpathway typically consists of chemical bond-breaking and bond-formingsteps involving the hydride donor and acceptor. The atomic structure withmaximum energy along the scanned energy surface was used as the initialguess for a local TS optimization subsequently refined by the eigenvector-following method. After convergence of the TS optimization, we carriedout a frequency calculation to check that the optimized TS structure exhibits asingle, nontrivial imaginary mode, along which we relaxed the TS structure toobtain the connecting IS and FS structures. In practice, multiple imaginaryfrequencies below 100i cm−1 were present in some of the IS, TS, and FSstructures. These modes with such small imaginary frequencies were notinvolved in the HT process and corresponded to rotations of H2O moleculesin the explicit solvation layer adsorbed on the GaP(110) surface. Numerousattempts to refine the IS/TS/FS structures could not remove these modes. Thevariation of the system’s electronic energy among these attempts was smallerthan 10 meV. Therefore, all of the imaginary modes with frequencies below100i cm−1 were ignored and considered as numerical noise in our HT barriercalculations. The impact of ignoring these small-imaginary-frequency modes onthe system’s vibrational free energy is discussed in SI Appendix, section S3. Forthe IS and FS structures in the 2-PyH−*–CH2–CH2F case and the FS structurein the 2-PyH−*–CH=CH2 case, one imaginary mode with a respective frequencyof 134i, 293i, and 164i cm−1 was present and could not be removed despite anumber of structural-refining attempts. The variation in the system’s energyacross these structural-refining attempts was <10 meV. This minor noise in theIS/FS structural optimization does not affect any of the conclusions in this work.

We also calculated zero-point energies, thermal corrections, and entropyterms (at T = 298.15 K) using the harmonic oscillator approximation for vibrations.Because the atoms of adsorbates and the surface do not have rotational andtranslational degrees of freedom, we only included vibrational contributions tothe free energy in the cases involving a cluster representing a semi-infinite sur-face. Isolated solvated molecule calculations properly included the rotational andtranslational contributions in the free energies in addition to vibrational ones.

Data Availability. Input files for geometry optimization and single-pointenergy calculations are available in SI Appendix. Cartesian coordinates ofall of the structures generated in the protonation free-energy calculationsand HT barrier calculations are shown in Dataset S1.

A

B

Fig. 3. Correlation between the descriptor ΔN and (A) predicted 2-PyH−*–Rprotonation free energies (at pH 5.2) and (B) predicted barriers for HT from2-PyH−*–R to CO2. The blue and orange dashed lines (least-squares best fitswith equations and R2 shown) depict the linear scaling relationships in A andB, respectively.

Protonation free energy (eV)

HT

bar

rier

(eV

)

2-PyH-*

2-PyH-*-CF3

2-PyH-*-CN

2-PyH-*-CHO2-PyH-*-COOH

2-PyH-*-CH2OH

2-PyH-*-CH2F 2-PyH-*-CH=CH2

y = 0.7066x + 0.6923R = 0.78751

0

0.2

0.4

0.6

0.8

1

1.2

-0.6 -0.4 -0.2 0 0.2 0.4 0.6

2-PyH-*-CH2-CH2F

Fig. 4. Correlation between the protonation free energies and the HT bar-riers of 2-PyH−*–R. The black data point is for the unsubstituted 2-PyH−* usedas a reference. The black dashed line (least-squares best fit with equation andR2 shown) illustrates the scaling relationship between the protonation freeenergy and the HT barrier. The green shaded region depicts where the overallHT rate RHT(2-PyH

−*–R) is larger than RHT(2-PyH−*). The green shaded region

ends where the 2-PyH−*–R protonation free energy equals +0.06 eV. Thegreen data points correspond to the promising –R candidates, while the reddata point cases are unlikely to improve the hydride donor’s performance.

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Supporting Information. Energies of all possible configurations for 2-PyH−–R

test cases, free-energy diagram and IS/TS/FS atomic structure for the HTprocess 2-PyH–*–COOH + CO2 sol → Py*–COOH + HCOO−

sol, discussion aboutthe impact of neglecting small imaginary-frequency modes on the system’svibrational free energy, and input files for our geometry optimization andsingle-point energy calculations are available in SI Appendix. Cartesian co-ordinates of the reactant and product structures for the 2-PyH−*–R protonation

free-energy calculations and the IS, TS, and FS structures for the HT reactions areavailable in Dataset S1.

ACKNOWLEDGMENTS. The authors acknowledge financial support from theAir Force Office of Scientific Research under Air Force Office of ScientificResearch Award FA9550-14-1-0254. We thank Dr. Gopalakrishnan Sai Gautamand Ms. Nari Baughman for helping to edit this manuscript.

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