The origin of the chemical shift non-equivalence lies deep within the concept of prochirality. The desymmetrization of 22-P atoms in a single step by weak interactions with a chiral guest proves to be particularly useful for the e.e. determination. To illustrate 10CSA interactions with α2β2-P, a conformational search was performed using the α2β2-P[SO4 2-][HSO4 -]4 structure for building starting geometries. Corresponding noncovalent interactions of the major conformer are illustrated in Figure . When racemic and non-racemic mixtures of 10CSA were applied in the system at constant concentrations it was found that ∆σ of the o-ArH, CH3, and N-H peaks rely on respective % of the e.e. value (Figure ). At the racemate point, the isochronous profile of 22-P is restored since the chiral information is transmitted in equal proportions from both the chiral components. Since the ∆σmax value of the inner core system is substantially higher than that of other regions, the resolution, of which e.e. can be detected, is considerably enhanced. Astonishingly, at as low as 2% e.e., two distinct N-H resonance singlets (∆σ 0.022 ppm.) can clearly be identified, while the other regions show only a broadening of the signals. Plotting the differences in the chemical shifts of split peaks against the % e.e. values revealed a linear dependency with the R 2 values being above 0.997 and the inner N-H fitting R 2 = 0.9994 (Figure ). The linear fit of the plots is a fundamental property in unlocking the easy calibration of the referenced systems for quick detection of the e.e. value (a detailed example shown in SI; Figure ). Moreover, spatially distant neighboring protons from N-H offer another important feature. Sharp and well-isolated singlets do not suffer from any vicinal scalar J-couplings or roofing effects underlining the simplicity in tracking chiral compositions. Overall, monitoring changes of this inner core system in a model chiral environment demonstrates a powerful tool for easy and sensitive detection of enantiomeric compositions. The magnitude of non-hydrogen ∆σ relies on the spatial positions, distances, and interactions with chiral guests. The further the stereogenic center of a chiral guest from the host molecule, the weaker the chirality transfer is. Interestingly, this principle was previously well-defined in the porphyrin-based hostguest chirogenic systems by using circular dichroism spectroscopy. The dependence of the non-equivalency to the chiral guest location can be illustrated by 13 C and 15 N NMRs. (For detailed comparison of non-hydrogen resonances see Table ). When 22-Pꞏ10CSA(S) was compared to racemic 22-Pꞏ10CSA(SR), most of the macrocyclic ring system exhibited ∆σmax > 0.3 ppm with the central two nitrogen atoms having ∆σmax = 1.67 ppm (Figure ). Nevertheless, due to the greater distance from the active site, most of the phenyl ring resonance signals remained isochronous. Despite this, two particularly different scenarios were portrayed by the o-Ar-13 C NMR signals. The ∆σmax between 15 and 20 positions yielded excellent separation (~1.3 ppm), whereas the 5 and 10 6 imposed only marginal ∆σmax (0.04 ppm). A closer examination of the crystal structure of α2β2-P[SO4 2-][HSO4 -]4 revealed a closer distance between C15 6 and C20 than between C5 6 and C10 6 (~9.311 Å), subsequently forming a narrow channel for the chiral guest to occupy (Figure ). Moreover, the calculated chemical shifts of non-hydrogen atoms in 22-Pꞏ10CSA(R) using the GIAO-B3LYP/6-311++G**//BP86-D3BJ/def-SVP method and SMD solvent model correlated well with the splitting patterns observed experimentally (for more information check SI, Table ). Of note, in 1 H NMR the 15 and 20 positions had similar ∆σmax. Hence, while hydrogens of the o-Ar group were more likely to form weak interactions with the chiral compounds, the corresponding ∆σmax value of carbon resonances hinges on the spatial arrangements and proximity to the guest. Comparison of the 22-Pꞏ10CSA(S and SR) splitting resonance signals to other atropisomeric species is detailed in SI (Table ).