Joanna S.
Stevens
*ab,
Sarah
Coultas
c,
Cherno
Jaye
d,
Daniel A.
Fischer
d and
Sven L. M.
Schroeder
*ef
aSchool of Chemical Engineering and Analytical Science, The University of Manchester, Oxford Road, Manchester, M13 9PL, UK
bThe Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK. E-mail: jstevens@ccdc.cam.ac.uk
cKratos Analytical, Wharfside, Trafford Wharf Road, Manchester, M17 1GP, UK
dNational Institute of Standards and Technology, Gaithersburg, MD 20899, USA
eSchool of Chemical and Process Engineering, University of Leeds, Leeds, LS2 9JT, UK. E-mail: s.l.m.schroeder@leeds.ac.uk
fFuture CMAC Group, Research Complex at Harwell, Chilton, Didcot, OX11 0FA, UK
First published on 18th February 2020
Short, strong hydrogen bonds (SSHBs) have been a source of interest and considerable speculation over recent years, culminating with those where hydrogen resides around the midpoint between the donor and acceptor atoms, leading to quasi-covalent nature. We demonstrate that X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy provide deep insight into the electronic structure of the short OHN hydrogen bond of 3,5-pyridinedicarboxylic acid, revealing for the first time distinctive spectroscopic identifiers for these quasi-symmetrical hydrogen bonds. An intermediate nitrogen (core level) chemical shift occurs for the almost centrally located hydrogen compared to protonated (ionic) and non-ionic analogues, and it reveals the absence of two-site disorder. This type of bonding is also evident through broadening of the nitrogen 1s photoemission and 1s → 1π* peaks in XPS and NEXAFS, respectively, arising from the femtosecond lifetimes of hydrogen in the potential wells slightly offset to either side of the centre. The line-shape of the core level excitations are thus related to the population occupancies, reflecting the temperature-dependent shape of the hydrogen potential energy well. Both XPS and NEXAFS provide a distinctive identifier for these quasi-symmetrical hydrogen bonds, paving the way for detailed studies into their prevalence and potentially unique physical and chemical properties.
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Fig. 1 Schematic of hydrogen potential energy wells for the range of hydrogen bonding interactions and Brønsted proton transfer between an oxygen donor and nitrogen acceptor. |
Significant variations in physicochemical properties can result with full proton transfer such as solubility, bioavailability and colour.18–21 These are of interest in practical applications, as they allow tuneability to product requirements. Very importantly, identification of the extent of proton transfer underpins the regulatory definitions of pharmaceutical salts and co-crystals.19,22 Specific behaviour has also been associated with the intermediate scenarios, such as stabilisation of photoactive proteins23 and transition states in enzymatic reactions with low-barrier hydrogen bonds,15,24,25 and stabilisation of hydrogen around the midpoint in the solid state for single wells through femtosecond low-frequency lattice vibrations.7,10–12
Despite the potential ramifications for alteration of physicochemical properties and the regulatory requirements, there is no single, unequivocal experimental basis for identifying a low barrier or single well hydrogen bond and quasi-centred hydrogen. Experimentally accessible indicators include the short donor–acceptor distance via X-ray diffraction, closely matched pKa values, 1H NMR chemical shifts to high frequency, low isotope fractionation factors, and unusual primary isotope shifts,3,15,26 although these exhibit a spectrum of values that overlaps with those of ordinary hydrogen bonds.26 Neutron diffraction can accurately locate hydrogen positions, including situations where when hydrogen is quasi-centred, but it still requires particular care and expertise in recognising and examining electron density maps/displacement ellipsoids, while not auto-refining the hydrogen onto the donor or acceptor. Additionally, crystallography and NMR spectroscopy provide a time-average of the dynamic hydrogen population and are not suited to provide information about any proton migration dynamics within these bonds.
We have previously shown that the core level spectroscopies, X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine-structure (NEXAFS) spectroscopy distinguish incisively between hydrogen bonding and Brønsted proton transfer in organic systems,27–36 with their strong sensitivity to the local environment and bonding around the probed atoms. The movement of a proton between donor and acceptor leads to a strong chemical shift in the core level photoemission from the acceptor moiety – the XPS chemical shift of the acceptor depends strongly on the distance of the proton (hydrogen).34 Localised, 2-site disorder is also easily recognisable from the presence two distinct photoemission signals, with the population occupancies reflected by the area under the peaks. With knowledge of core level binding energy shifts from XPS, deeper insight into local bonding can be obtained by probing unoccupied molecular orbitals energies with NEXAFS spectroscopy, including the influence of hydrogen bonding;21,34,37–41 moreover, the ultrafast timescale of these spectroscopic techniques42–44 makes them ideal for probing dynamic processes. XPS and NEXAFS are therefore ideally placed to also probe short hydrogen bonding, providing information not only on the location of hydrogen along the proton transfer axis, but also the presence (or absence) of any population occupancies or dynamic processes.
In the following, we will describe how XPS and NEXAFS involving the 1s core level of nitrogen acceptors in pyridine-dicarboxylic acid (PDCA) systems (Fig. 2) reliably characterises the varying positions in the proton transfer pathway. Using crystalline 3,5-PDCA as our model system, we show for the first time that core level spectroscopies unequivocally detect a single-well, quasi-centred hydrogen bond. This will be contrasted with results for hydrogen residing on the donor atom in 2,6-PDCA and proton transfer to the acceptor atom in 2,3-PDCA (Fig. 2).
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Fig. 2 Chemical structures of 3,5-PDCA, with its quasi-centred hydrogen bond, and its non-ionic (2,6-PDCA) and ionic protonated (2,3-PDCA) analogues. |
3,5-PDCA has a short intermolecular donor–acceptor distance (2.52 Å, Table 1), with hydrogen residing around the centre.10 This system provides an ideal case study for XPS/NEXAFS because it involves a single nitrogen acceptor and an oxygen donor, providing a simple emission spectrum from both moieties that does not overlap with emission lines from other species. The strength of the interaction with the nitrogen acceptor group, and hence the chemical shift of the nitrogen 1s core level emission line, is expected to be intermediate between those of a protonated nitrogen acceptor and a nitrogen acceptor in an ordinary hydrogen bond, in which the hydrogen remains located close to the donor group. Temperature-dependent measurements also permit investigation of stabilisation of the hydrogen position around the centre of the donor–acceptor bridge10–12 through ultrafast dynamic, slight lattice vibrations.7
d(NH)/Å | d(OH)/Å | d(NO)/Å | d(NH)–d(OH) | d(NH)/d(NO) | |
---|---|---|---|---|---|
a List of crystal structures and CSD refcodes in the ESI. Diffraction data collection at 283–303 K with a neutron source, apart from 2,6-PDCA with XRD. A hydrogen bonded carboxylic acid dimer is formed for 2,6-PDCA, rather than an OHN intermolecular hydrogen bond, so the NH and NO values for 2,6-PDCA are the closest intermolecular distances for the atoms. | |||||
2,6-pya | 4.575 | 0.774 | 5.335 | 3.08 | 0.858 |
3,5-py | 1.308 | 1.218 | 2.525 | 0.090 | 0.518 |
2,3-py | 1.036 | 1.845 | 2.725 | −0.809 | 0.380 |
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Fig. 3 Hydrogen bonding present in the crystal structures of 3,5-, 2,6-, and 2,3-PDCA,10,45,46 showing no proton transfer for 2,6-PDCA, intermediate hydrogen location between nitrogen and oxygen for 3,5-PDCA, and full proton transfer for 2,3-PDCA. |
In 3,5-PDCA, the hydrogen is residing almost equidistant from both the donor oxygen and acceptor nitrogen atoms (i.e. the OH and NH distances are similar), in an extremely short intermolecular OHN hydrogen bond (Table 1 and Fig. 3).10 The nitrogen 1s XP spectrum reflects this through a slightly asymmetric signal centred at a binding energy of approximately 400.15 eV, with the asymmetric peak maximum offset by 0.4 eV to lower energy. This binding energy is intermediate to that of the unprotonated (no proton transfer) and the protonated nitrogen (proton transfer) in the two reference systems (Fig. 4), with a far greater chemical shift for 3,5-PDCA than observed for formation of ordinary hydrogen bonds (ca. ≤+0.2 eV for the acceptor atom),33,49–51 but much less than observed for protonation of nitrogen acceptors (ca. +2 eV, Fig. 4).27–35 Comparison of the donor-hydrogen (OH) and acceptor-hydrogen (NH) distances involved in the intermolecular interaction in 3,5-PDCA from neutron diffraction (Table 1) shows hydrogen is located almost centrically between the (original) donor oxygen and acceptor nitrogen atoms,10 with a slight offset towards oxygen at RT, mirroring the chemical shifts from XPS.
Notably, there is significant broadening and reduced intensity (Fig. 4) of the nitrogen 1s signal relative to the non-protonated and protonated forms, with a 2 eV full-width half-maximum (FWHM) while the reference systems have narrow emission lines with a FWHM of 1.2 eV. We note here that all other emission lines from 3,5-pyridinedicarboxylic acid are not broadened, thus ruling out surface charging, roughness or particle size variations as causes for the observed broadening of the nitrogen 1s emission line. Moreover, we will also see further below that similar broadening occurs in the N K-edge NEXAFS.
The broadening thus indicates nitrogen is experiencing more than one type of chemical environment in 3,5-PDCA. The crystal structure does not indicate inequivalent nitrogen atoms – there is only one molecule, and thus one nitrogen atom, in the asymmetric unit.10 More specifically, there was no indication of hydrogen disorder over two distinct positions (CN, COOH and C
NH+, COO−) in the X-ray and neutron diffraction analysis.10
If the 3,5-PDCA system exhibited hydrogen disorder across two distinct sites, a non-protonated CN and a protonated C
NH+, then the XP spectra would resemble that of 2,6- and 2,3-PDCA superimposed on one another, i.e. a double peak spectrum with maxima at about 399.1 and 401.3 eV, with the relative area intensities providing the hydrogen occupancies on the two sites. For example, a 30
:
70 distribution of H across the N and O sites would be reflected by two well-resolved peaks comprised of a 30% signal at the binding energy for C
NH+ and a 70% signal for C
N (Fig. 5). Such a spectrum is clearly not observed in Fig. 4 for 3,5-PDCA.
The absence of 2-site disorder leaves a dynamic process as an explanation for the observed broadening of the nitrogen 1s photoemission line, for which XPS is ideally placed to probe, with the ultrafast nature of the photoemission process (sub-fs).42–44 Indeed, a previous molecular dynamics (MD) study7 investigated the location of hydrogen in the short hydrogen bond between oxygen and nitrogen in 3,5-PDCA. It indicated small magnitude dynamic migration of the hydrogen around the midpoint between the donor and the acceptor (Table 2), but never localised on one side.10 The MD simulations predicted a symmetrical, broadened single minimum potential energy well for hydrogen (Fig. 1) at the temperature for which its distance to the acceptor and donor atoms becomes equivalent. Asymmetric distributions were then predicted for higher and lower temperatures with a slightly offset hydrogen position.7 The broadened minimum allows the proton wavefunction to extend, facilitating slight movements to either side of the midpoint,7 even at room temperature. This sharing of the hydrogen electron density between nitrogen and oxygen is opposed to its localisation in the deeper potential well of an ordinary hydrogen bond (Fig. 1).2,3
d(NH)/Å | d(OH)/Å | d(NO)/Å | d(NH)–d(OH) | d(NH)/d(NO) | |
---|---|---|---|---|---|
15 K | 1.213 | 1.311 | 2.523 | −0.098 | 0.481 |
296 K | 1.308 | 1.218 | 2.525 | 0.090 | 0.518 |
The MD simulations7 indicated rapid movement of the hydrogen by up to ca. 0.1 Å between nitrogen and oxygen on the order of 100 fs (10−13 s), with the quasi-central position stabilised through low frequency lattice vibrations (and not excited N–H vibrational precluding conventional vibrational broadening visible in XPS for simple hydrocarbons52,53). This is significantly faster than typical proton hopping/exchange easily resolvable with XPS, such as with imidazole (around 10−10 s),43,44 although still considerably slower than the photoemission timescale (∼10−16 s).42–44 When there are significant chemical shifts associated with the location of hydrogen in a dynamic population, the lineshape of XPS can therefore provide a snapshot of the hydrogen distribution across the accessible positions in the potential well. We therefore conclude that the asymmetric broadening towards high binding energy in the room temperature nitrogen 1s emission line for 3,5-PDCA (Fig. 4) reflects a situation in which more hydrogens are, on average, localised marginally closer to the oxygen atom, but still with a significant population located marginally closer to nitrogen – i.e. reflecting an asymmetric single minimum potential energy well.
A previous temperature-dependent neutron diffraction study10 indicated the likely dynamic nature of this system, with observation of very slight hydrogen movement towards the nitrogen acceptor at lower temperatures (Table 2). The authors could not rule out the temperature-dependent changes being related to some experimental error, but concluded there was no evidence of two-site disorder based on examination of H-atom displacement ellipsoids, and suggested a single potential well rather than a low barrier double well based on similar behaviour with deuterium (correlating with the MD simulation results7). We examined the temperature-dependence of the nitrogen 1s photoemission line of 3,5-PDCA. The results shown in Fig. 6 show an increasing intensity of the high binding energy side of the emission line with decreasing temperature, which is associated with the movement of hydrogen slightly towards the nitrogen acceptor. Compared to the nitrogen 1s XPS peak seen at RT (303.15 K, 30 °C; grey, Fig. 6), that at low temperature (123.15 K, −150 °C) is approaching symmetrical (black, Fig. 7), indicating that hydrogen prefers to reside almost equidistant from the oxygen donor and nitrogen acceptor at this temperature – i.e. approaching a symmetrical single minimum potential energy well with decreasing temperature. In contrast, heating the sample up to 578.15 K (305 °C), results in a more asymmetric peak than at RT (Fig. 6) confirming that higher temperature favours the localisation of hydrogen slightly closer to the oxygen donor.
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Fig. 6 Nitrogen 1s XPS spectra of 3,5-PDCA with temperature: 123.15 K (−150 °C, black), 303.15 K (30 °C, grey), and 578.15 K (305 °C, black dashed). |
Turning to the nitrogen K-edge NEXAFS (Fig. 7) of the three systems, we observe in all spectra a sharp pre-edge resonance that arises from transitions from the nitrogen 1s core level to unoccupied valence orbitals with p character (N 1s → π*). In line with the XPS results, a slightly asymmetric, broadened nitrogen 1s → 1π* resonance occurs for the pyridine CN nitrogen environment of 3,5-PDCA, which is again at an intermediate energy between those of the non-protonated and protonated nitrogen analogues (Fig. 7).
The asymmetric lineshape and observed chemical shifts seen in the NEXAFS data mirror the slight offset towards oxygen seen with XPS (i.e. signal slightly closer to CN than C
NH+ for 3,5-PDCA). This provides evidence that the chemical shifts in NEXAFS are mainly dominated by the variations in the nitrogen 1s core level binding energies, rather than variations in the energies of the π* orbitals. We have previously observed a similar initial-state domination of NEXASF chemical shifts.38
The timescale of NEXAFS absorption is determined by the core hole lifetime, in analogy to XPS. NEXAFS can therefore also act to provide snapshots of all the possible hydrogen position occupancies (i.e. population) relative to nitrogen. The shape and asymmetry of the peaks can again be used to trace the slight migration of the hydrogen around the midpoint and its preferred location at a particular temperature (as noted with neutron diffraction, Table 2)10 and reflect the change in potential energy well from slightly asymmetric towards symmetric predicted by the MD simulations as the midpoint is approached.7 The temperature-dependent NEXAFS (Fig. 8) is consistent with the conclusions drawn from XPS, in that the nitrogen π* resonance becomes more symmetrical at low temperature (131 K, −142.15 °C) as more hydrogen atoms move slightly closer to the nitrogen such that the distribution becomes more evenly spread, i.e. towards a symmetrical, single potential well.
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Fig. 8 Nitrogen K-edge NEXAFS spectra of 3,5-PDCA with temperature: 131 K (−142.15 °C, black) & 301 K (25.85 °C, grey). |
The results for both XPS and NEXAFS show how sensitive they are as probes for the hydrogen location in these donor–acceptor systems. With the latest generation of XPS and NEXAFS equipment permitting rapid turnaround measurements on a timescale of minutes, they should be considered complementary techniques for crystallographic analysis of hydrogen bonding dynamics. The ultrafast nature of core level spectroscopies is a distinct advantage over NMR in that line-shape analysis should allow drawing conclusions about the location and population of sites in the crystal structure. The value of core level spectroscopies thus lies particularly in their ability to distinguish unequivocally between different types of interactions involving hydrogen, effectively probing different points in the continuum from hydrogen bonded (X–H⋯Y) through to proton transfer (−X⋯H–Y+). The short, quasi-centred hydrogen bond can then be envisaged as the middle of this continuum or proton transfer pathway/reaction (X⋯H⋯Y), with XPS able to successfully identify this.
There are also short hydrogen bonds where the acceptor-hydrogen distance is less than in a more conventional hydrogen bond, but the hydrogen electron density remains localised on the donor atom.54–56 This is opposed to a short hydrogen bond in which the hydrogen is more centrally localised between acceptor and donor and more even sharing of electron density as observed in the present study. In the latter case, the decision as to which of the atoms hydrogen is covalently bound to becomes blurred.10,11,56 Based on the results reported here we predict that core level spectroscopies can distinguish these two cases, because no line broadening would be observed for the former, and given non-protonated and protonated references the chemical shift indicates the relative distance of hydrogen from the donor/acceptor.
Finally, we would like to note once more that classifying such bonds reliably can have substantial real-world impact, for example in the pharmaceutical industry, where incorrect classifications may potentially determine intellectual property rights and regulatory requirements.19,22,57 In fact, one could argue that where the electron density in a hydrogen bond becomes quasi-centred10,11,12,58 it becomes less clear whether these interactions even fall under the common notion of a hydrogen bond1 – at the very least some nomenclature for easily referring to this type of symmetric/quasi-centred hydrogen bond would be beneficial. The ability to experimentally distinguish between these different types of bonding should not, therefore, be underestimated.
Footnote |
† Electronic supplementary information (ESI) available: List of crystal structures and CSD Refcodes. See DOI: 10.1039/c9cp05677g |
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