To or not to how does methanol dock onto anisole?

Anisole offers two similarly attractive hydrogen bond acceptor sites to an incoming hydrogen bond donor: its oxygen atom and its delocalized p electron system. Electronic structure calculations up to the CCSD(T)/AVTZ level suggest an isoenergetic situation for methanol after harmonic zero point energy correction, within less than 1 kJ mol . Linear infrared absorption spectroscopy in the OH stretching fundamental range applied to a cold supersonic jet expansion of anisole and methanol in helium shows that the oxygen binding site is preferred, with about 20 times less p-bonded than O-bonded dimers despite the non-equilibrium collisional environment. Accidental band overlap is ruled out by OH overtone and OD stretching spectroscopy. Furthermore, the diagonal anharmonicity constant of the OH stretching mode is derived from experiment and reaches 80% of the monomer distortion found in the methanol dimer, as expected for a weaker hydrogen bond to the aromatically substituted oxygen. To reconcile these experimental findings with ab initio theory, accurate nuclear and electronic structure calculations involving AVQZ basis sets are required. Dispersion-corrected double-hybrid density functional theory provides a less expensive successful structural approach.


Introduction
Anisole (methoxybenzene) is one of the best-studied aromatic systems in the gas phase, also in terms of molecular complexes. 1,2 Brutschy et al. investigated its water clusters 3,4 and found the first water to bind to the oxygen of anisole in the electronic ground state, whereas Li + is predicted to prefer p binding. 5 A secondary water docking minimum with a p bond was initially elusive, 4 but computationally identified later on. 6 However, it does not play a direct role in the large amplitude motion of the water molecule around the anisole oxygen, which even gives rise to an anomalous structural isotope effect. 6,7 In the mixed trimer, two water molecules bridge the anisole plane 8 from the oxygen atom to the p system. 4 The complex between phenol and anisole also opts for the oxygen binding site. 9 For 1,2-dimethoxybenzene, 10 water similarly prefers oxygen coordination. In contrast, indole prefers the p system of furan over the O coordination as a consequence of the stronger delocalization of the oxygen lone pairs in this heterocycle. 11 A close competition between OH-O and OH-p binding sites has recently been reported for 2,3-benzofuran, 12 where it actually leads to a coexistence of the two docking motifs for both water and methanol in supersonic jet expansions.
By combining methanol with anisole, there are thus promising ways to influence the docking preferences in one or the other direction using chemical substitution and it makes sense to start with a detailed study of the parent complex.
Based on the full body of experimental findings, it is plausible but far from certain that methanol will prefer the oxygen docking site of anisole. To the best of our knowledge, no microwave, infrared or IR/UV double resonance spectra of this binary complex have been reported so far, whereas its components are very well investigated. 13,14 Also, OH-O and OH-p isomers of methanol complexing the anthracene analog of anisole have been identified long ago by UV hole burning spectroscopy 15 and in that work, the study of methanol-anisole was actually suggested. In the context of calibrating quantum-chemical methods for the description of polar vs. dispersive interactions of alcohols with ethers, 16 we found that the most reliable among the routinely applicable methods predict the two docking sites to be essentially isoenergetic for methanolanisole, with at best a slight preference below 1 kJ mol À1 for the oxygen binding site. This has triggered a detailed supersonic jet study of the binary mixture, using a pulsed slit nozzle synchronized to the rapid scans of a FTIR spectrometer. As the isomerization barrier between the two docking sites is not very pronounced, one can expect a rather rigorous experimental ordering for the relative binding energies of the two isomers. This provides valuable benchmarks for theory, once the anharmonic nature of hydrogen bond interactions 17,18 is captured sufficiently well.
Beyond the relative binding energies of interest in the present work, absolute binding energy determinations for aromatic complexes can be quite demanding. 2 The value derived for water-anisole from two-color dissociative photoionization is 15.4(5) kJ mol À1 , 19 which may serve as a calibration value for the current investigation despite its large amplitude motion. 7 The present study forms the starting point of a systematic variation of the alcohol donor and ether acceptor molecules to map out the borderline between the OH-O and OH-p docking preference and compare the findings to high level and more approximate quantum chemical calculations. 20

Methods
The technique used to generate cold methanol-anisole complexes has been described before. 21 They are formed transiently after the pulsed adiabatic expansion of the compound-loaded helium carrier gas through a 600 mm long slit nozzle into a large (420 m 3 ) vacuum chamber. The size of the vacuum chamber prevents interactions of the expansion with background gas in the immediate neighborhood of the nozzle for a fraction of a second despite the limited pumping capacity (E2500 m 3 h À1 ). During this short time, full scans of an FTIR spectrometer (Bruker IFS 66v/S) at 2 cm À1 resolution (1.5 cm À1 in the OD case) are conducted through the adiabatic expansion using lenses. Feeble changes in the interferometrically modulated beam of a 150 W tungsten filament lamp are detected by a cooled 2 mm InSb or 3 mm InGaAs detector. Afterwards, the vacuum system recovers from the gas pulse for a time period of up to one minute. Scaling of the absorption features with concentration and pressure discriminates dimers from monomers and larger clusters. A comparison to single component expansions identifies mixed complexes. Linearity of the detection allows extraction of approximate relative intensities in different spectral ranges. Care is taken to correct for detector differences by reference measurements. Anisole and methanol are supplied to the carrier gas via temperature-controlled saturators. Overtone spectra are shown after linear baseline correction in the case of methanol-anisole.

Exploratory quantum chemical results
The size of the methanol-anisole complex and even somewhat larger systems allows for fairly rigorous ab initio electron correlation computations of the dissociation energy, which may be compared to dispersion-corrected double-hybrid 30 and hybrid density functional results. 27 The latter is rather useful for predictions of vibrational spectra and can thus also be employed for an estimate of the harmonic zero point energy, although some deficiencies for methanol OH stretching and librational modes have recently been noted. 31,32 Table 1 provides an overview of the results obtained by such size-scalable methods for triple-zeta basis sets, distinguishing between the electronic structure level used for structure optimization and the level used to compute the electronic energy, always estimating the zero-point energy difference of the competing complexes harmonically at the B3LYP-D3/def2-TZVP level. Relative energies of the O-bonded structures refer to the dissociation energy of the most stable p-bonded isomer, and the O-bonded absolute dissociation energies are listed explicitly in the last column (see also Tables S1-S3 in the ESI †).
We note that the role of (harmonically estimated) zero point energy is to favor the OH-p structure relative to OH-O by about 0.8 kJ mol À1 (B3LYP-D3/def2-TZVP, differing by 0.1 kJ mol À1 among a range of settings, see Table S2 in the ESI †). This is qualitatively reasonable, because OH-O hydrogen bonds are considerably more anisotropic, thus accumulating intermolecular zero point energy in their librational subspace. 32 We expect that the value could change by at most AE0.5 kJ mol À1 at higher levels of harmonic analysis. Taking this for granted, Table 1 suggests that p bonding is slightly favoured at the MP2 level, whereas O bonding is more favoured at the DFT levels. CCSD(T) calculations predict a perfectly balanced situation between the two docking sites, which is apparently only weakly dependent on the level used to obtain molecular structures.
One should also note that some of the fluctuations in the energy difference are comparable in size to some of the fluctuations in absolute binding energy. This suggests that the experimental investigation of such energy differences in the docking site provides useful benchmarks for theory, rather than being blurred by systematic error compensation. The two docking sites are sufficiently different in nature to turn the energy gap into a critical test for theory. Finally, the effects of counterpoise correction indicate that there is room for improvement in the basis set size although the table suggests that this is a less important issue for the energy difference of interest. Table 1 Energy DE h 0 /(kJ mol À1 ) of the OH-O-bound methanol-anisole complex relative to the OH-p-bound complex and its absolute dissociation energy D h 0 /(kJ mol À1 ), as obtained for different combinations of the optimized structure and electronic (el.) energy combined with B3-D3 harmonic zero point energy, all employing triple zeta basis sets a

Structure
El. energy

OH stretching fundamental results
If one assumes that the dominant peak in the OH fundamental spectrum at 3598 cm À1 (center trace of Fig. 1) is due to a single conformation of the mixed methanol-anisole dimer, its proximity to the methanol dimer absorption (MM) strongly indicates oxygen docking (MA O ). In line with expectations of an electron-deficient ether oxygen due to aromatic delocalization, the shift from the monomer (3686 cm À1 ) is just 80% of that in the methanol dimer (3575 cm À1 ). Towards 3620-3640 cm À1 , where OH-p docking would be expected to manifest itself, 33 only a very weak feature is observed (MA p at 3629 cm À1 ). Even when accounting for a reduced IR visibility of this weaker hydrogen bond by a factor of 2-3, we find that this minor component corresponds to about 20Â lower abundance in the slit jet expansion. This translates into a ratio between the energy difference DE and RT c of about 3, where T c is the conformational temperature, i.e. the effective Boltzmann temperature where interconversion between the two docking sites freezes in the expansion. Estimates from calculations suggest an easily surmountable barrier between the docking motifs on the order of 3 kJ mol À1 . Even with a very low conformational temperature of 40 K (a more typical T c value would be closer to 100 K 34 ), one can still derive an energy penalty DE of at least 1 kJ mol À1 for the p docking site. More likely, this energy penalty is expected somewhere in the 1-2 kJ mol À1 range.

Towards possible explanations
There is thus a clear disagreement between standard quantumchemical predictions and the experiment for the docking preference of methanol in the case of anisole. Harmonically zero-point corrected energy calculations predict an equivalence within 1 kJ mol À1 whereas the experimental spectra suggest a preference for the O docking by at least 1 kJ mol À1 . On the theoretical side, it may be that the structural predictions are inaccurate, the relative electronic energy could be biased towards p docking or the harmonic approximation might be insufficient for the zero-point energy difference. On the experimental side, only an accidental overlap of spectral transitions is conceivable as a qualitative error source, whereas extremely efficient interconversion between the two docking sites in the jet expansion would have to be invoked to explain the observed quantitative suppression of p docking despite a sub-kJ mol À1 energy difference. We start with the experimental analysis, ruling out an accidental overlap of two conformations in the strong 3598 cm À1 signal attributed to the mixed dimer MA O . An analogous experiment for CH 3 OD also yields a single dominant mixed dimer band, as shown in the bottom trace of Fig. 1. Similar to the parent isotopologue, the shift from the monomer amounts to 80% of that of the methanol dimer. With a FWHM of 3.8 cm À1 , it is even more narrow than the parent transition (4.5 cm À1 ). Persistent overlap is incompatible with this observation due to the significantly different anharmonic contributions in OH and OD stretching modes among the two docking sites. 35 The weak satellite band to higher wavenumbers (MA p ), which we tentatively assign to a minor OH-p contribution, is now even weaker. This meets the expectation that zero-point delocalization effects (which are more important for H than for D) tend to stabilize OH-p over OH-O, in agreement with the harmonic prediction. To further exclude that the dominant transition is mostly due to p docking, the OH overtone region was probed. There is only a single mixed dimer contribution above the noise level (upper trace in Fig. 1), from which an enhanced diagonal anharmonicity constant of À96 cm À1 compared to the methanol monomer value 35,36 of À86 cm À1 is derived. Furthermore, this overtone transition is attenuated by a factor of 500(150) relative to the fundamental (estimated error in parentheses), very characteristic of OH-O interactions. For comparison, the methanol dimer has an even larger diagonal anharmonicity constant of À99 cm À1 and a similarly high attenuation factor of 320(90) for its donor overtone. 36 If there was a significant OH-p contribution, it would show up prominently in the overtone region due to its smaller anharmonicity and much weaker attenuation of the intensity. Another experimental piece of evidence against significant p docking is the dominant fundamental transition wavenumber itself (3598 cm À1 ), which differs markedly from that of the methanol-benzene complex 33 (3639 cm À1 ). Because it may be argued that the aromatic p system is more electron rich in anisole than in benzene, we have also recorded the spectrum of the methanol-toluene complex, obtaining an OH-p fundamental wavenumber of 3632 cm À1 (see the insert MTol in Fig. 1). This is still 34 cm À1 higher than the dominant methanol-anisole feature, but in very satisfactory agreement with the weak methanolanisole band marked MA p at 3629 cm À1 .
The observed discrepancy must therefore be due to the limited quality of most theoretical predictions listed in Table 1. A structural explanation may at first sight appear unlikely, as dispersioncorrected B3LYP calculations should capture the essence of both OH-O and OH-p interactions reasonably well and the CCSD(T) calculations predict essentially the same energy difference for all three optimized structures (Table 1). However, inspection of the corresponding OH-O structures ( Fig. 2(a)) shows that the methyl group is positioned differently in the MP2-optimized structure. It interacts more closely with the benzene ring than in the two hybrid DFT structures, where the hydrogen bond is more structuredetermining. In contrast, the most stable OH-p structure is rather similar across the three methods ( Fig. 2(b)). To decide which of the OH-O structures is closer to reality, their electronic energy at the highest affordable level must be investigated and it will be shown below that the MP2-optimized OH-O structure is indeed more remote from the true structure. The calculations also reveal a second OH-p 0 arrangement, which is more p-centered (Fig. 2(c), see also Table S4 in the ESI †). Although it is energetically higher than the OH-p structure shown in (b) at all investigated computational levels, it profits from a lower zero point energy and may fall within 1 kJ mol À1 of the more stable p structure. Inspection of its structure reveals that the OH-p 0 configuration actually involves a more exclusive interaction with the p system, whereas the more stable structure additionally profits from two reciprocal methyl CH-O contacts in the 0.27-0.28 nm range. In the analogous toluene case (Fig. S11, and Tables S12 and S13 in the ESI †), where at least one of these contacts is lost, the two p-bonded structures become energetically nearly degenerate, but should still be spectrally distinguishable. The interaction potential between the OH group and the extended p system is generally expected to be relatively flat, possibly too flat to support the population of more than one of the connected potential wells in a supersonic jet expansion with its isomerising collisions. However, there is a sizeable statistical advantage for p-oriented structure formation associated with this, compared to the more narrow potential energy funnel offered by the oxygen atom in anisole. The fact that none of the two p structures is observed experimentally in methanol-anisole in significant abundance despite this statistical advantage points even more to a missing stabilization of OH-O at most computational levels summarized in Table 1.
The second possible source of computational error refers to the electronic energy at the best structures. Table 1 includes calculations at the CCSD(T)/AVTZ level, considered to be reasonably accurate for absolute predictions and even more so for the relative energy prediction relevant to this work. It does indeed show a slight electronic preference for OH-O of 1.0 kJ mol À1 , but this is not enough to tip the balance towards OH-O docking after zero point energy correction. Counterpoise correction for the AVTZ basis set superposition error goes in a favorable direction for the energy difference, but is only on the order of 0.1 kJ mol À1 (Table 1) and thus insufficient to explain the discrepancy, even more so if one only includes 50% of this correction. 37 To further explore basis set incompleteness effects, we have thus extended the MP2-contribution to the AVQZ level. Surprisingly, this increases the relative MP2 stability of the OH-O structure by up to 1 kJ mol À1 (Table 2). Obviously, the two interaction sites show a very different basis set dependence. With the CCSD(T) correction on top, this means that the OH-O structure is now electronically up to 2.0 kJ mol À1 more stable than the most stable p complex. After harmonic zero point energy destabilization, this provides the first systematic ab initio prediction which is qualitatively compatible with experiment. We note that the somewhat less ab initio and much more economical doublehybrid approach (B2P-D3 in Table 2) is rather close. Even the B3-D3 hybrid functional prediction starts to overlap the experimental range, if optimization is performed using the AVTZ basis set instead of our standard def2-TZVP basis set. One may thus conclude that a correct balance between the O and p docking sites requires basis sets of quadruple-zeta quality for ab initio methods or at least AVTZ for hybrid DFT approaches. Furthermore, one can now judge the quality of the three structural predictions in Fig. 2 by applying the CCSD(T)-corrected MP2/AVQZ level to each of them. It turns out that the double hybrid structure yields the lowest OH-O and OH-p energies and is thus most likely the best relative structural prediction (see also Table S5 in the ESI †). It is followed at a close distance by the B3LYP structure (with a balanced energy penalty of 0.3-0.4 kJ mol À1 for both docking sites), whereas the MP2/AVTZ structures are found to deviate by 0.9 kJ mol À1 for the OH-O site and by only 0.1 kJ mol À1 for the OH-p docking site. Clearly, the MP2/AVTZ approach provides an imbalanced structural description of the two methanol coordination options and should not be trusted for relative energy predictions. This parallels the overestimation of stacked aromatic interactions at the MP2 level. 38 Our best electronic prediction is thus that the OH-O structure is more stable than the OH-p structure by 2 kJ mol À1 and the second OH-p 0 structure is less stable than OH-p by more than 1 kJ mol À1 .
Thirdly, the zero point energy correction itself needs to be addressed. As mentioned before, the B3-D3 approach predicts a harmonic advantage for OH-p of 0.8 kJ mol À1 . This is also basis set dependent, changing to 1.0 kJ mol À1 at the AVTZ level. On top of this harmonic uncertainty, one has to address anharmonic corrections. Even at the zero point level, anharmonicity effects on the order of 1-2% will persist, but most of those are expected to cancel for the difference between the two docking sites. 39 Unfortunately, vibrational perturbation treatments to include such effects [40][41][42] are not always reliable over the entire spectrum of normal modes for floppy systems. 43 While they provide fairly reliable high frequency mode corrections, 36 they occasionally tend to predict unphysical anharmonicity effects for large amplitude low frequency modes. In the present case, imaginary anharmonic frequencies were persistent for the OH-O and OH-p 0 isomers. Therefore, we have to constrain the anharmonic analysis to the three most important differences between the docking sites, namely diagonal OH correction, torsional anharmonicity and OH-torsional coupling. 32 As shown in the ESI † (Table S7), the diagonal anharmonicity is more pronounced in the OH-O case, thus stabilizing the OH-O isomer. However, this correction amounts to less than 0.05 kJ mol À1 relative OH-O stabilization at the zero point level (B3LYP-D3/def2-TZVP, a level reproducing methanol and methanol dimer anharmonicities reasonably well, 36 see Table S7 in the ESI †). The methanol torsional mode acquires a significantly higher frequency in the OH-O case, a major reason for the total harmonic zero point energy stabilization of the OH-p docking site. If one trusts the vibrational perturbation theory analysis at least qualitatively and combines the effect of up to two modes with torsional character (see Table S8 in the ESI †), the diagonal anharmonic effect of torsion is to attenuate the zero point energy stabilization by less than 0.1 kJ mol À1 . The OH-torsional coupling is also more pronounced for OH-O docking and of similar size, but with opposite sign (ESI, † Table S8). This qualitatively counteracts the two diagonal terms, as observed in the methanol dimer OH stretching shift. 31 Indeed, one can expect that the net anharmonic effect on the zero point level difference between the two docking sites will be smaller than 0.1 kJ mol À1 and its net sign remains unclear. A converged full-dimensional anharmonic calculation of this effect would be desirable, 44 but so would be a further improved harmonic description. At the best available levels, zero point energy shrinks the predicted sequential energy spacing between the OH-O, OH-p and OH-p 0 structures by a factor of two, to 1.1 and 0.7 kJ mol À1 , respectively. This is just in borderline agreement with our experimental interpretation.
A side effect of the anharmonic calculations is the OH overtone prediction, where vibrational perturbation theory has proved to be fairly reliable. 32 The predicted B3LYP-D3/ def2-TZVP increase (in absolute value) of the anharmonicity constant in the OH-p complex amounts to 40% of that in the methanol dimer, whereas the observed increase is between 70 and 80% of the methanol dimer value, consistent with the predicted value for the OH-O complex of 71% (Table S7 in the ESI †). This provides further evidence for the OH-O structural assignment of the mixed dimer.
Another side effect of the anharmonic calculations is the availability of approximate fundamental/overtone intensity ratios for the donor OH stretching mode of methanol. 42 The perturbation theory results (Table S7 in the ESI †) confirm that the OH-O intensity ratio of methanol-anisole (300 at the B3LYP-D3/def2-TZVP level) is of the same order of magnitude as the methanol dimer (480, experimentally one finds 320(90) 36 ), whereas for OH-p docking it is predicted below 100 and thus closer to the monomer (the monomer intensity ratio is predicted at only 5). Any OH-p fraction in the supersonic jet expansion should thus have an overproportionally higher visibility in the overtone spectrum, but none is detected within the available signal-to-noise ratio. Quite in contrast, the observed intensity ratio of 500(150) is definitely too high to allow for significant OH-p contributions in the fundamental range, further reinforcing the experimental finding. This remains valid if a small part of the mixed dimer fundamental intensity stems from larger clusters in the concentrated expansion.
It is instructive to extract the actual D3 energy contributions to binding in the different complex isomers. At the B3LYP-D3 level, we find 12 kJ mol À1 dispersion energy gain for the OH-O  complex and 17-18 kJ mol À1 for the two OH-p complexes (see Table S6 in the ESI †). London dispersion interaction is seen to be a major stabilization force for OH-p docking, adding 50% to the dispersion contribution present in the O-bonded complex. Expectedly somewhat less satisfactory is the predictive power of our quantum chemistry for the OH wavenumber difference between the two observed docking sites, experimentally indicated at 31 cm À1 . The B3-D3 harmonic prediction is 50 cm À1 (55 cm À1 for the AVTZ basis set), vibrational perturbation theory improves to 44 cm À1 , still 40% too high. Much of this deviation is to be blamed on the systematic overestimation of harmonic OH-O red shifts at all but the highest levels of electron correlation, 31 whereas OH-p shifts behave better. 29 As in similar cases, 45 monomer-shifted or -scaled harmonic predictions for the OH stretching fundamental slightly overestimate the absolute OH-p wavenumber (by 6 cm À1 at the B3-D3 level, but coincidentally 0 cm À1 with the AVTZ basis set) and underestimate the OH-O wavenumber (by 11 cm À1 at the B3-D3 level, but 22 cm À1 for the AVTZ basis set, see Table S7 in the ESI †).
Finally, we judge the reliability of the best calculated absolute dissociation energies by transferring our findings to the OH-O bonded water-anisole complex. The B2PLYP-D3/AVTZ optimized water-anisole structure (Fig. S9 in the ESI †) has an electronic dissociation energy relative to relaxed monomers of 21.9 kJ mol À1 at the MP2/AVQZ + DCCSD(T)/AVTZ level, which shrinks to 15.0 kJ mol À1 (15.1 kJ mol À1 ) after including the harmonic B3LYP-D3/def2-TZVP (AVTZ) zero point energies (Table S10 in the ESI †). As anharmonic corrections are likely to increase this value slightly, agreement with the experimental value of 15.4(5) kJ mol À1 19 could hardly be better. Thus, we can expect that not only energy differences but also absolute energies are quite accurate at this level. While the size-scalable consistent B3LYP-D3/def2-TZVP result expectedly overshoots (17.8 kJ mol À1 ), B3LYP-D3/AVTZ (14.7 kJ mol À1 ) is in line with the best value, as for methanol-anisole. We can therefore be confident that the zero-point-corrected dissociation energy of methanol-anisole in its preferred OH-O conformation is close to 20 kJ mol À1 and that the most stable OH-p conformation is at least 1 kJ mol À1 or 5% less stable.

Conclusions
By a combination of highly sensitive fundamental isotopologue and overtone spectroscopy of methanol-anisole mixtures in supersonic jet expansions, we firmly establish that the methanol molecule forms a hydrogen bond with the ether oxygen of anisole, whereas docking onto the p system is at least 1 kJ mol À1 less attractive and therefore hardly observable in the jet spectra.
A reasonably elaborate theoretical prediction including three independent structure optimizations, canonical CCSD(T)/AVTZ electronic energies, 50% MP2 counterpoise correction, harmonic B3LYP-D3/def2-TZVP zero-point energy correction and anharmonic estimates for off-diagonal and diagonal OH stretching contributions amounts to an energy penalty of about 0.4 kJ mol À1 for the OH-p structure. This is not quite sufficient to explain more than one order of magnitude less abundance in the supersonic jet expansion experiment, unless the conformational temperature was far lower than in other molecular systems. However, if we switch from AVTZ to an AVQZ basis set for the MP2 part, the OH-p structure is destabilized by another 1.0 kJ mol À1 , shifting theory into the experimentally compatible energy range. Similar results are obtained at the B3LYP-D3/AVTZ level and also at the B2PLYP-D3/AVTZ level, encouraging their use as workhorses for the prediction of energy preferences and spectra of a larger range of alcohol-ether complexes. Our results show that relative docking energies between O and p sites represent exquisitely sensitive testing cases for quantum chemical descriptions of weak to medium-strength hydrogen bonds. Due to the close energy balance, methodical variations cause qualitative changes and computational error compensation becomes unreliable as a consequence of the different nature of oxygen and p cloud docking. Higher level computational approaches 46,47 are invited to test our findings.
By subtle chemical modifications of the donor and/or acceptor (e.g. ring methylation), we expect to render OH-p docking slightly more attractive and thus clearly observable in supersonic jet expansions in competition with OH-O docking, even in the overtone range and also probing structural isotopic effects. This could turn the present single-sided experimental benchmark for hydrogen bond docking sites into a valuable double-sided benchmark at the sub-1 kJ mol À1 accuracy level.