Proton Transfer, Hydrogen Bonding, and Disorder: Nitrogen Near-Edge X-ray Absorption Fine Structure and X-ray Photoelectron Spectroscopy of Bipyridine–Acid Salts and Co-crystals

Abstract

The sensitivity of near-edge X-ray absorption fine structure (NEXAFS) spectroscopy to Brønsted donation and the protonation state of nitrogen in the solid state is investigated through a series of multicomponent bipyridine− acid systems alongside X-ray photoelectron spectroscopy (XPS) data. A large shift to high energy occurs for the 1s → 1π* resonance in the nitrogen K-edge NEXAFS with proton transfer from the acid to the bipyridine base molecule and allows assignment as a salt (CNH + ), with the peak ratio providing the stoichiometry of the types of nitrogen species present. A corresponding binding energy shift for CNH + is observed in the nitrogen XPS, clearly identifying protonation and formation of a salt. The similar magnitude shifts observed with both techniques relative to the unprotonated nitrogen of co-crystals (CN) suggest that the chemical state (initial-state) effects dominate. Results from both techniques reveal the sensitivity to identify proton transfer, hydrogen bond disorder, and even the potential to distinguish variations in hydrogen bond length to nitrogen. ■ INTRODUCTIONProton (hydrogen) transfer can be thought of as one of the simplest chemical reactions, ranging from complete transfer from an acidic to a basic moiety (protonation through Brønsted donation) to varying degrees of sharing through hydrogen bonding. Whether Brønsted proton transfer occurs has a profound effect on the location of protons in crystal structures and influences chemical and physical properties. These interactions can be employed to target properties of solid forms (crystal engineering), with particular relevance to the pharmaceutical industry where acid/base guest molecules can be combined with active ingredients to tailor properties such as solubility and bioavailability through formation of salts and cocrystals. 1−4 Other relevant fields are organic ferroelectrics, 5 energetic materials, 6 and the design of materials with targeted optical properties such as color 7 and luminescence. 8,9 Even among hydrogen bonds, the level of interaction with the donor and acceptor atoms can vary significantly, from relatively weak to strong with quasi-covalent character, 10 and there is also the possibility of disordered hydrogen bonds. 11 While X-ray diffraction (XRD) and solid-state nuclear magnetic resonance spectroscopy (ssNMR) are often techniques of choice for structural characterization, 2,11−14 they are not always unambiguous with regard to proton locations (although further clarity can often be obtained by neutron diffraction). 11,13−16 The importance of accurate characterization of salts vs co-crystals based on this relatively small difference in proton location should not be underestimated, particularly with the wider implications for intellectual property and regulatory control in the pharmaceutical industry. 4,17 X-ray photoelectron spectroscopy (XPS) has recently been shown to unequivocally identify whether intermolecular proton transfer occurs in a range of two-component systems and distinguish protonation (salt...

Intermolecular bonding of hemin in solution and in solid state probed by N K-edge X-ray spectroscopies

“…[26] However, recent studies of bipyridine acid salts and co-crystals indicated that the effect of final state effects on the relative positions of * features are negligible, even when comparing bipyridine nitrogen species in very different local chemical environments. [27] Further inspection into the individual components C and D uncovers that the feature C remains roughly constant in peak width from Figure 3a to 3c, while the feature D becomes broader and relatively more intense upon hemin aggregation. The mechanism of this distinct peak evolution is likely due to the different extents of the orbital involvement in the hemin intermolecular bonding interactions which will be discussed in detail for Figure Figure 3 can therefore be visualized as the MOs presented in Figure 4.…”

In Situ Solid‐State Reactions Monitored by X‐ray Absorption Spectroscopy: Temperature‐Induced Proton Transfer Leads to Chemical Shifts

“…The nitrogen K-edge NEXAFS of the yellow form I at ambient temperature clearly shows two primary peaks at 397.7 and 399.2 eV (Figure 2), representing promotion of an N 1s electron to the first p* unoccupied molecular orbital. This is followed by the low intensity, secondary p* resonances from transitions to higher-energy unoccupied p* orbitals, as well as broader s* resonances that are more susceptible to variations in geometric structure [15,16] once sufficient energy is absorbed to overcome the ionization potential >405 eV, represented by the step up in intensity (a detailed fit of the data is provided in the Supporting Information).The lowest energy p* resonance at 397.7 eV arises from the non-protonated pyridine C=N nitrogen environment (C=N 1s → 1p* transition). [16] In contrast, that at 399.2 eV is shifted to higher energy with the decrease in electron density at nitrogen arising from the positively charged protonated C=NH + nitrogen (C=NH + 1s → 1p*).…”

“…[16] It is therefore ideally placed to identify the protonation states in the yellow and red forms of 4BPY-SQU, and only requires ~10 minutes for acquisition of a spectrum. The nitrogen K-edge NEXAFS of the yellow form I at ambient temperature clearly shows two primary peaks at 397.7 and 399.2 eV (Figure 2), representing promotion of an N 1s electron to the first p* unoccupied molecular orbital.…”

“…[16] In contrast, that at 399.2 eV is shifted to higher energy with the decrease in electron density at nitrogen arising from the positively charged protonated C=NH + nitrogen (C=NH + 1s → 1p*). [16] The areas under the peaks for C=N and C=NH + provide the ratio of transitions from each species, and are comparable since peak width naturally increases with energy (as it is inversely proportional to the lifetime of the transition). [14] The chemical shifts and In situ heating of the yellow form I was then performed to trace the transition to the red form II over 185°C.…”

“…The p*r egion of NEXAFS (involving transitions from the core atomic level to the p LUMO) is highly sensitive to the local chemicale nvironment of an atom, in particulart he chem-ical state, and has recently been demonstrated to distinguish between hydrogen bondinga nd proton transfer in pharmaceuticalc o-crystals and salts. [11] Therefore, it is ideally placed to identify the protonation states in the yellow and red forms of 4BPY-SQU, and only requiresa pproximately ten minutes for acquisitiono faspectrum. The nitrogen K-edgeN EXAFS of the yellow form Ia ta mbient temperature clearly shows two primary peaks at 397.7 and 399.2 eV (Figure2), representing promotion of an N1se lectron to the first p*u noccupied molecular orbital.…”