3.9.2. Special Case: SSMF3 and F-SAPT Partitioning Analyses for Complexes of BCX··· Gly

The SSMF3 model for hexa-*p*-*tert*-butylcalix[6]arene produces as many as 150 fragments; therefore, the tables analogous to Table 4 were shifted to the Supplementary Information. The SAPT0 interaction energies for complexes *al*-BCX··· Gly and *wc*-BCX··· Gly are close to those for the CX counterpart (−59.7 mH and −57.7 mH for *al*, −52.0 mH and −50.0 mH for *wc*, for CX and BCX, respectively), but the for *pc*-BCX the interaction energy is 11 mH lower than for the unsubstituted case. Naively, one could assume that it is the attraction with the *tert*-butyl groups, which makes the total interaction energy more negative, but the sum of interaction energies between fragments made from *tert*-butyl with Gly gives a negligible contribution. Therefore, the influence of the *tert*-butyl substituents is more subtle–their presence leads to geometry modifications, which, in turn, allow for a better arrangement of Gly on top of the *pc*-BCX. Similarly, as in the unsubstituted case, there is a set of interaction energies of about −19 mH each, which contain the same type of an H-bond between the carboxyl group of Gly and the OH-1 group (note that for the pristine calixarene OH-1 and OH-4 groups etc. are equivalent, see Figure 2). Again, the presence of the calixarene unit 2 causes an enhancement of the electronegative character of the O-1 atom through the intramolecular H-bond with the OH-2 group, which explains its weaker attraction to Gly (to −13 mH for fragments with the unit 2 removed). The first

significant difference appears for numerical values of interaction energies for fragments with the unit added on the other side (the unit 6) of the unit 1. Although the intramolecular H-bond between OH-1 and OH-6 is created, as in the CX case, it weakens the attraction to Gly by 2 mH only, while for the CX case this change amounts to 5 mH. Still, this difference alone does not explain the 11 mH gap between the total interaction energies for the CX and BCX for this conformer, and other differing factors should be looked for. It turns out that the missing difference can be found from the examination of fragments, which contain units 4 and 3 of BCX and have interaction energies of −14 to −15 mH. In these fragments, one H-bond between the H atom from the OH-4 group and the NH2 group of Gly can be found, while the neighboring OH-3 group forms the intramolecular H-bond acting as the H donor, i.e., it enhances the negative character of the O-4 atom. The latter explanation is confirmed by comparison with fragments without the OH-3 group, for which the interaction energy changes to −10 mH. Summarizing, in comparison to the CX case, the interaction with the NH2 group is much stronger and it is this interaction which according to the SSMF3 partitioning is responsible for the stronger attractive force for the *pc*-BCX in comparison to the unsubstituted calixarene. It is also worth noting that the direction of the primary H-bond for the NH2 group changes, i.e., this group becomes the H acceptor for the BCX case. The F-SAPT partitioning confirms these findings: there is still a strong bond of −15 mH between the COOH and OH-1 groups, but the attraction of the OH-4 to the amino group is stronger (−15 mH) than for the CX case. This new intermolecular H-bond causes a distortion of one from the intramolecular H-bonds in the BCX, what can be also observed from the pattern of I-SAPT interaction energies between the hydroxy groups, where instead of one strong attraction of −15 mH between OH-1 and OH-6 only a weak one of −4 mH remains.

The *al*-BCX··· Gly complex is of the inclusion type, and the Gly molecule resides in the cavity created by units 3, 4, and 5 of the BCX, as for the *al*-CX counterpart. The fragments which give the largest attractive SSMF3 contributions (−18 mH) contain the phenyl and hydroxy groups from units 1 and 2, and–similarly as for the *al*-CX case – one of them donates its H atom to the NH2-Gly group forming an H-bond, and another one enhances this interaction through a creation of the intramolecular H-bond with the O-2 atom. This effect can be estimated as about 6 mH, based on the energy of the fragment without the unit 1 (−12 mH). There is another group of fragments with no analogs for the CX case, which gives rise to contributions of about −15 mH. It turns out that they all contain the H-bond between NH2 (the H donor) and the OH-6 group (H··· O distance of 2.005 Å) and additionally possess the phenyl and hydroxy groups from the neighboring unit 5. The lack of these two groups leads to a strong decrease in attraction (to −8 mH), but for the *al*-BCX geometry, the intramolecular H-bond between the OH-5 and OH-6 groups cannot exist; therefore, the reason for a large attraction in the former case is the direct interaction of the phenyl and hydroxy groups of unit 5 with Gly. The latter conclusion is confirmed by the interaction energy of about −9 mH for fragments, which contain the Ph-5 and OH-5 groups, but no other groups of these types. It should be noted that a relatively large distance between Gly and such fragments suggests that the interaction should be of an electrostatic type since electrostatic contributions are known to be long-ranged. There are also fragments containing the phenyl and hydroxy groups of the unit 4, which attract Gly with the strength of −10 mH. It is evident from the geometry analysis that the OH-4 group cannot effectively participate in any H-bond with Gly, but since the carboxy group is positioned quite close to the Ph-4 (the closest distance between the hydrogen atom of COOH and the carbon atom is about 2.5 Å), one can predict a formation of an unusual Hbond between this hydrogen and the *π* cloud of the phenyl ring. Note that this distribution of interaction strengths is different from the *al*-CX case, where contributions as large as −26 mH are present, so–surprisingly–such close total interaction energies result from the summation of contributions of a partially different origin. The F-SAPT partitioning confirms the existence of strong bonding between the OH-2 and NH2 groups (−21 mH), as in the CX case. However, contrary to the CX case, the carboxy group is attracted mostly

not to the Ph-5 group, but to a closer Ph-4 group with a remarkable strength of −24 mH. Nevertheless, in both cases, the existence of the H-*π* bond can be postulated based on the position of the hydrogen atom and on the analysis of SAPT components. Another feature of the binding pattern is the existence of a secondary H-bond, in which the NH2 group donates a hydrogen atom. This H-bond can be identified based on the analysis of the interaction between the NH2 and OH-6 (−5 mH, with about +10 mH from the exchange component). The strong attraction from unit 5 found in the SSMF3 partitioning is also reproduced here as a strong electrostatic-dominated interaction between the COOH and Ph-5 (−10 mH). It should be emphasized that the F-SAPT and SSMF3 partitionings for the *al*-CX and *al*-BCX complexes with Gly reveal that the Gly molecule is attracted by the cavity from several sites with similar strength. The geometry analysis shows that this relatively small molecule seems to fit well into the small cavity of the *al* conformer; therefore, these complexes represent examples of the enhancement of the interaction due to a confinement effect.

The main features of the complex of Gly with the *wc*-BCX are similar to the *wc*-CX case. The first set of interaction energies of about −23.5 mH corresponds to fragments containing the phenyl groups plus hydroxy groups from units 5 and 6. The OH-5 group serves as an H donor, and the OH-6–as an H acceptor for two H-bonds with the NH2- Gly. Since the fragment without the OH-5 group, but with the OH-6 group remaining, has the interaction energy reduced to −16 mH, the strength of the second H bond can be estimated as about 7 mH. The addition of the phenyl and OH groups from the unit 1 leads to the increased attraction (−21 mH), which can be explained by the intramolecular H-bond creation between the OH-6 and OH-1 groups, which increases the electronegative character of the O-6 atom (this H-bond is also seen from the I-SAPT analysis). The next sets of interaction energies correspond to the fragments containing either both phenyl and hydroxy groups from units 2 and 3 (energies of −15.5 mH), or having groups from unit 3 only, which reduces the interaction to −10 mH. Since the OH-3 group donates its H atom to the oxygen from the carbonyl group of Gly (the H··· O distance of 1.99 Å) and the OH-2 group is a hydrogen acceptor for the NH2 group; therefore, two H-bonds are present here, and the H-bond between the OH-2 and amino groups can be estimated as about 5.5 mH from a difference analysis. The F-SAPT partitioning results are in line with these findings. Firstly, the most important interaction of −19 mH exists between the amino and OH-6 groups. The carboxy group forms a weaker bond with the OH-3 group with the strength of −7 mH. The analysis of SAPT components confirms that these two bonds are H-bonds. The amino group is also connected with the groups OH-1 and OH-2, but from these two pairs, the first one is dominated by electrostatics, while the second again represents an H-bond. It is interesting to note that the distance between the corresponding hydrogen atoms of the amino group and oxygen atoms of the hydroxy groups is only 0.15 Å longer (2.22 *versus* 2.04 Å) for the electrostatic driven interaction and differences in the total interaction energies are also not very large (−4 mH *versus* −6 mH). Nevertheless, in the second case, one has a significant first-order exchange component of 7 mH, which is counterbalanced by other components, from which the electrostatics gives the most negative contribution (−9 mH). It should be noted that for the CX case, both these interactions were of the H-bond type.
