Supramolecular cages as differential sensors for dicarboxylate anions: guest length sensing using principal component analysis of ESI-MS and 1H-NMR raw data

Abstract

Dynamic covalent libraries (DCLs) have been widely used in the development of differential sensors. Inspired by recent studies which use supramolecular recognition systems for sensing, we report the use of a tris(-pyridylmethyl)amine (TPMA)-based supramolecular cage as a differential sensor for dicarboxylate anions. In particular, a library of molecular cages constituted by linkers differing in size and flexibility was allowed to equilibrate toward a series of guests differing in molecular size. The differential system was able to discriminate a series of dicarboxylates depending on their chain length. This differentiation was evaluated through the application of the Principal Component Analysis (PCA) method using interpolated and raw data obtained from ESI-MS. Interestingly, while the ¹H NMR spectra of the differential system did not allow for the discrimination of the analytes by the naked eye, PCA of the raw data from the spectra revealed information on the chain length of the guest and also on the odd-even character of the carbon chain.

Fig. 1. Selectivity profiles for cages (a) C_n@E-E-E, (b) C_n@P-P-P and (c) C_n@X-X-X among the guest series ranging from C₄ to C₁₄ (I_Cn/∑I_Cn represents the value of the relative intensity of the monoisotopic peak of each inclusion species among the guest series). The counteranion is perchlorate for the cage metals and triethylammonium for the carboxylate guests.

Fig. 2. (a) DCL using different linkers E, P and X. The ratio between the complex, guest, linkers and p-anisaldehyde is 2 : 1 : 9 : 12 ([1] = 1.6 mM, [C_n] = 0.8 mM, and [E] = [P] = [X] = 2.4 mM [p-anisaldehyde] = 9.5 mM). (b) ESI-MS spectrum of the mixture in the presence of C₈ as the guest after 72 hours.

Fig. 3. (a) ESI-MS of the DCL ranging from C₅ to C₁₄. Ten isotope clusters corresponding to the ten possible cages are present (doubly charged peaks for each included system). (b) Principal component analysis scores of the spectral data for the E + P + X experiment taking into account the normalized intensities of the monoisotopic peaks in four different experiments and (c) PCA of the normalized raw data of the MS spectra.

Fig. 4. On the left: ¹H NMR spectra (301 K, DMSO-d₆) of the DCL in the presence of the guests ranging from C₅ to C₁₄. On the right: PCA performed considering four regions of the ¹H NMR spectra (a) 7.9–8.0 ppm, (b) 8.3–8.6 ppm, (c) 8.9–9.3 ppm and (d) 7.7–7.9 ppm.