All the capsules described so far possess a plane of symmetry due to chiral self-discrimination during the self-assembling process. This equilibrium was observed in 1 H-NMR the first time our group prepared a SubPc-based capsule.11
Turning upside-down the equilibrium between the enantiomers of the SubPc would give rise to capsules containing each enantiomer of the SubPc, M or P. This might be a step forward in the separation of the enantiomers of SubPcs. So far, M and P enantiomers of SubPcs have been discriminated by chiral HPLC.34 Thus, there is a strong need to develop a chiral discrimination approach that could potentially be applied to higher quantities of starting material.
To this end, a chiral ligand (s-BINAP) was chosen to arrange the coordination positions of the metal in a way that prevents the formation of the meso cage (Figure 29).
Figure 29. Schematic representation of Pt(S-BINAP) complex coordinating two SubPcs (only one pyridyl substituent of each one is shown). The distribution of the coordination positions
prevents the formation of the capsule with a plane of symmetry.
In principle, two situations might be envisaged in self-assembly with this metallic complex:
34(a) C. G. Claessens, T. Torres, Tetrahedron Lett., 2000, 41, 6361-6365 ; (b) N. Kobayashi, T.
Nonomura, Tetrahedron Lett., 2002, 43, 4253-4255.
- Stabilization of [M,M] and [P,P] capsules. In this case, we would obtain a mixture of the two capsules, each one containing only one kind of enantiomer. Thus, separation of M and P isomers could not be directly achieved, and further work addressed to selective crystallization of one of the capsules should be done.
- Stabilization of [M,M] or [P,P] capsule. That involves selectivity towards one of the enantiomers. The other one might remain in solution or might coordinate to Pt, but to afford specie(s) different from homodimeric capsules.
Self-assembly was carried out as described above, and 1H and 31P-NMR spectra of the product were recorded. 31P-NMR spectrum showed two singlets at ~ -3 ppm. 1H-NMR spectrum analysis was difficult due to the abundance and overlapping of signals in the aromatic region. These results, at first, made us think that equilibrium had not been reached.
Hence, self-assembly process was followed by 31P-NMR. Pt(S-BINAP)OTf2 was added portionwise to a solution of SubPc 11 until the right stoichiometry was reached. The mixture was allowed to equilibrate after each addition. Results are shown in Figure 30.
40 35 30 25 20 15 10 5 0 -5 -10 -15 -20 -25 -30 -35 -40
Figure 30. 31P-NMR spectra of self assembly of 11 with increasing amounts of 12e.
Coordination of SubPc 11 to Pt is observed in the growth of the signals around -3 ppm.
When the amount of Pt complex 12e approaches the accurate ratio, two peaks become
dominant in that region. Finally, the solution was stirred at room temperature overnight.
After that period, almost total disappearance of the singlet corresponding to 12e was observed. The solution was then concentrated, and upon addition of diethyl ether the product crashed out as a purple powder. Size exclusion chromatography of this solid was carried out, and two purple fractions were isolated. The major one was the heaviest compound and its 31P-NMR spectra presented the two singlets previously observed in the reaction mixture. The second fraction was the starting SubPc (Figure 31).
Figure 31. 1H-NMR spectra of the products isolated in size-exclusion chromatography (blue line corresponds to fraction 1, capsule 13e; and black line corresponds to fraction 2, SubPc 11).
31P-NMR spectrum of the first fraction might be explained by the presence of those two capsules. Besides, a closer analysis of 1H-NMR spectrum allowed identification of some of the signals of the SubPc, and it could be seen that each signal is duplicated.
This fact is also consistent with the hypothesis of formation of both [M,M] and [P,P]
capsules.
A representation of [M,M] and [P,P] capsules is shown in Figure 32. In each of these capsules, there are elements of symmetry relating every atom in the upper SubPc with the lower one. For example, in Figure 32, some protons that are related through a improper rotation axis are indicated. Thus, each capsule has to give rise to only one set of signals in NMR. Moreover, as the relative disposition of SubPcs in each capsule is different, it should be possible to distinguish them in NMR spectroscopy.
Figure 32. Representation of [M,M] (left) and [P,P] (right) capsules. In [M,M] isomer, protons marked in blue are related to the one marked in orange through symmetry elements.
Finally, and in order to completely discard the selectivity towards one of the enantiomers, capsule 13e was decomposed by column chromatography in silica gel.
SubPc 11 was thus recovered, and its optical rotation was measured, as well as the one of the starting material (racemic mixture). In both cases polarized light passed through the sample without appreciable deviation. From this result we conclude the SubPc recovered from the capsule contains both enantiomers. The conclusion is, thus, that stabilization of [M,M] and [P,P] capsules was achieved.
Attempts of crystallization of any of these capsules with slow vapour diffusion failed.
3.2. Characterization
All compounds were characterized by 1H, 31P and 19F-NMR, IR, UV-visible spectroscopies and ESI-mass spectrometry.
The most remarkable feature of 1H-NMR spectra is the downfield shift of the proton in ortho to the N of the pyridine due to the coordination of pyridine to the metal centre.
This signal appears at 9.01 ppm in the free SubPc and shifts up to 9.65 ppm in the case of capsules bearing dppp ligand. This downfield shift is lower in the case of dppf-capsules. 1H-NMR spectra also showed more defined signals for platinum capsules, revealing the less dynamic nature of the equilibria that occur in solution. In the case of 13b and 13d, bearing ferrocenyl secondary ligands, the loss of planar symmetry of the
ferrocene moiety in the capsules give rise to four signals (Figure 33). These results are consistent with the formation of the capsules.
Figure 33. Signals corresponding to ferrocene moiety in the 1H-NMR spectrum of 13b.
31P-NMR showed one singlet in all cases, accompanied by two 195Pt satellites in the case of 13c and 13d. The chemical shift of these singlets was different from the ones in the original metal complexes, thus showing that the chemical environment of P has changed after the self-assembly process.
Table 3. 31P-NMR chemical shifts for precursor metal complexes and capsules.
δ 31P (ppm) JPt-P (Hz)
12a 15.01 --
12b 46.17 --
12c -10.83 3818
12d 15.81 1074
13a 6.23 --
13b 27.89 --
13c -15.28 2988
13d 16.11 2988
ESI-MS spectrometry experiments also confirmed the formation of the assemblies.
Peaks corresponding to [M-OTf]+, [M-2OTf]2+, [M-3OTf]3+ were found in the spectra of 13a and 13c. Unfortunately, spectra of 13b and 13d could not be obtained; most Electrospray Ionization technique (ESI) permitted its extensive use in the Supramolecular Chemistry area, where it has been proved to be a useful tool for the study of the stability of host-guest complexes as well as to evaluate the strength of non-covalent interactions.35 Electrospray technique allows to establish a relationship between the areas of the peaks and the stability of the compound in MS experiments, thus making possible the comparison of compounds of a similar nature. However, this comparison must be taken carefully, since the response factors might not be the same for all the compounds analysed. This problem can be overcome thanks to MS/MS experiments, where all interactions due to the presence of the solvent disappear, and hence, complexes’ behaviour may vary from the one observed in simple MS also on the nature of the additional ligands (phosphine or amine in our case) present in
35 (a) D. V. Dearden, Host-guest molecular recognition without solvents (Ed.: L. Echegoyen, A.
E. Kaiser), Kluwer, Dordrecht, 1996, pp 229-247; C. A. Schalley, Int. J. Mass Spectrom., 2000, 194 11-39; (b) B. Baytekin, H. T. Baytekin, C. A. Schalley. Org. Biomol. Chem, 2006, 4, 2825-2841.
36 (a) R. Zadmard, A. Kraft, T. Schrader, U. Linne. Chem. Eur. J, 2004, 10, 4233-4239; (b) C. A.
Schalley, P. Weis., Int. J. Mass Spectrom., 2002, 221, 9-19; (c) C. A. Schalley, P. Ghosh, M.
Engeser. Int. J. Mass Spectrom., 2004, 232, 249-258; (d) R. W. Troff, R. Hovorka, T. Weilandt, A. Lützen, M. Cetina, M. Nieger, D. Lentz, K. Rissanen, C. A. Schalley. Dalton Trans., 2012, 41, 8410-8420; (e) C. L. Mazzitelli, J. Wang, S. I. Smith, J. S. Brodbelt. J. Am. Soc. Mass Spectrom., 2007, 18, 1760–1773;(f) M. A. Kaczorowska, A. C. G. Hotze, M. J. Hannon, H. J.
Cooper. J. Am. Soc. Mass Spectrom., 2010, 21, 300-309