Abstract
The properties of nitrogen centres acting either as hydrogen-bond or Brønsted acceptors in solid molecular acid-base complexes have been probed by N 1s X-ray photoelectron spectroscopy (XPS) as well as (15)N solid-state nuclear magnetic resonance (ssNMR) spectroscopy and are interpreted with reference to local crystallographic structure information provided by X-ray diffraction (XRD). We have previously shown that the strong chemical shift of the N 1s binding energy associated with the protonation of nitrogen centres unequivocally distinguishes protonated (salt) from hydrogen-bonded (co-crystal) nitrogen species. This result is further supported by significant ssNMR shifts to low frequency, which occur with proton transfer from the acid to the base component. Generally, only minor chemical shifts occur upon co-crystal formation, unless a strong hydrogen bond is formed. CASTEP density functional theory (DFT) calculations of (15)N ssNMR isotropic chemical shifts correlate well with the experimental data, confirming that computational predictions of H-bond strengths and associated ssNMR chemical shifts allow the identification of salt and co-crystal structures (NMR crystallography). The excellent agreement between the conclusions drawn by XPS and the combined CASTEP/ssNMR investigations opens up a reliable avenue for local structure characterization in molecular systems even in the absence of crystal structure information, for example for non-crystalline or amorphous matter. The range of 17 different systems investigated in this study demonstrates the generic nature of this approach, which will be applicable to many other molecular materials in organic, physical, and materials chemistry.
Highlights
The properties of nitrogen centres acting either as hydrogen-bond or Brønsted acceptors in solid molecular acid–base complexes have been probed by N 1s X-ray photoelectron spectroscopy (XPS) as well as 15N solid-state nuclear magnetic resonance spectroscopy and are interpreted with reference to local crystallographic structure information provided by X-ray diffraction (XRD)
Studies have shown that H-bonding and proton transfer in two-component systems can be distinguished using 15N solid-state nuclear magnetic resonance (ssNMR),[5,21,29,30,31,32] as for example shown for co-crystals and salts of a cancer-treatment API5 and for theophylline (1,3dimethyl-7H-purine-2,6-dione) systems.[21,28,30]
We reported that X-ray photoelectron spectroscopy (XPS) reliably detects proton transfer: a strong positive N 1s binding energy shift occurs due to protonation and identifies the formation of a salt.[21,28,30,33]
Summary
Single crystal X-ray diffraction (XRD) is most commonly used for determining whether proton transfer or hydrogen bonding takes place between acid and base components,[3,5,12,13,14,15,16,17,18] often in conjunction with an analysis of structural indicators such as bond angles and bond lengths.[3,12,16,19] the unequivocal determination of hydrogen positions is not always straightforward, with systems exhibiting proton disorder, temperaturedependent migration, or other unusual behaviour.[18]. As in our previous XPS study,[33] we incorporate several development API substances alongside a range of non-development acid–base complexes including theophylline, aminobenzoic, and isonicotinamide base components with different acid co-formers and differing acid strength These systems cover a wide range of pKa differences (DpKa), from À3.9 to +17.7, between the acceptor and donor functional groups, which will allow us to examine correlations between DpKa values and the chemical shifts observable by XPS and ssNMR in a systematic manner. Calculations were performed using Materials Studio version 4.4, as provided by Accelrys.[57] CASTEP DFT chemical shielding values (s) were obtained for the nitrogen atoms of the theophylline, 4-aminobenzoic acid, 3,5-diaminobenzoic acid, and isonicotinamide complexes using the previously reported[7,21,28,41,42,43] and new isonicotinamide co-crystal/salt crystal structures as input.
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