For the synthesis of the double-motorized porphyrin cage compoundZn3 (Supporting Information, Scheme S1) we followed the same
strategy as applied for the synthesis of mono-motorized cageZn2 .25 Compound Zn3 was obtained as
a mixture of six stereoisomers, i.e. three diastereomeric sets of
enantiomers. The different diastereomers Zn3a (first eluted,
C2-symmetric), Zn3b (second eluted,
non-symmetric), and Zn3c (third eluted,
C2-symmetric), see Figure 2, were separated by
conventional silica gel column chromatography. We resolved the
enantiomers of each diastereomeric set in order to be able to obtain
more information about the structures of the individual compounds by
chiroptical spectroscopy. Resolution was achieved by preparative chiral
HPLC using a Chiralpak IE column (Supporting Information, Figures
S1–S12). The ECD spectra of all the enantiomers of double-motorized
compound Zn3 were compared to the ECD spectra of the
corresponding single-motorized compound Zn2 (Figure 2A–B),
especially with respect to the Cotton effect of the molecular motor
absorption band at 250–300 nm and the Cotton effect of the Soret band
at 420–430 nm. Isomers with a positive Cotton effect of the Soret band
were assigned (+), and those with a negative Cotton effect of the Soret
band were assigned (−). The relative stereochemistry of Zn3awas identical to that of Zn2a , i.e. for both compounds
the motor and Soret CD bands had the same sign. Compounds Zn3cand Zn2balso
displayed similarities, in the sense that the motor and Soret CD bands
had opposite signs. Because
FIGURE 2 Spectroscopic comparison of motorized porphyrin cage compoundsZn2 and Zn3 . ECD spectra
(CH2Cl2, 298 K) of: (A) (+)-Zn2and (+)-Zn3 ; (B) (−)-Zn2 and (−)-Zn3 . (C)
Partial 1H NMR spectra (500 MHz,
CDCl3/CD3CN, 1:1, v/v, 298 K) ofZn2 and Zn3 . See Figure 1 for the proton assignments.
(D) Key NOEs (red arrows) of motor protons, spatial orientation, and
absolute configuration of isomers (+)-Zn3a , (+)-Zn3b ,
and (+)-Zn3c . The descriptors (R,P) and/or (S,M) represent the
point chirality and helicity of the molecular motor substituents in
their stable configuration, and the descriptor Sp (or
Rp, not shown in this Figure) represents the planar
chirality of the porphyrin cage.
of the presence of two motor substituents, the magnitude of the Cotton
effect of the motor substituents of Zn3a and Zn3c was
doubled with respect to that of Zn2a and Zn2b . The
non-symmetric compound Zn3b is different from all the other
compounds, since it contains two molecular motor substituents with
opposite chirality and, therefore, the motor CD band was absent.
Comparison of the CD spectra of Zn3 with those of Zn2allowed the determination of the absolute configuration of each isomer
(Supporting Information, Table S1). The 1H NMR spectra
of Zn2 and Zn3 gave additional evidence for the
above-mentioned differences and similarities between the compounds
(Figure 2C). In our previous work on single-motorized cage Zn2we showed that the chemical shifts of motor protons H-a and
H-b were indicative of the presence or absence of
intramolecular interactions between the naphthalene part of the motor
and the cavity of the porphyrin cage.25 The presence
of such interactions in compound Zn2b was evidenced by a strong
shielding effect on protons H-a and H-b , which is
caused by the parallel displaced π-π stacking of the naphthalene part of
the motor and the porphyrin. In contrast, this shielding effect was not
present in Zn2a and also not in theC 2-symmetric compound Zn3a , confirming
their similarity. It was observed, however, for one of the two motors of
non-symmetric compound Zn3b , and for both motors ofC 2-symmetric compound Zn3c . These
observations indicate similarities between the three-dimensional
structures of single- and double-motorized porphyrin cages Zn2and Zn3 . We conclude, therefore, that Zn3a contains
two molecular motors, which both are loosely connected to the cage with
no significant intramolecular interaction with the cage cavity. On the
other hand, Zn3b is equipped with one ‘loose’ molecular motor,
and one molecular motor that is intramolecularly ‘bound’ to the cavity.
Finally, compound Zn3c carries two ‘bound’ molecular motors. 2D
ROESY experiments confirmed the three-dimensional structures of the
different isomers of Zn3 (Figure 2D). The differences in steric
impediment between the ‘loose’ and ‘bound’ molecular motors may
translate into different affinities of the cage compounds for guest
molecules, i.e. it is expected that one or more ‘bound’ motor
substituents will inhibit binding of a guest in the cavity of hostZn3 .
We reported previously that porphyrin cage compoundsZn1 24 and Zn2 25display a high affinity for viologen guests. In this study, we evaluated
the binding affinities of the different isomers of Zn3 for
viologen guests V4 –V6 by fluorescence titrations
(Table 1). During these titrations, the porphyrins were excited at their
main Q-band (λex = 555 nm) to avoid in situ excitation
of the molecular motor substituents. The experiments revealed that
isomer Zn3a (two loose motors) binds all viologen guests with a
roughly two times higher association constant
(K a) than isomer Zn3b (one loose motor,
one bound motor). In turn, isomer Zn3b binds the guests with a
roughly two times higher K a-value than isomerZn3c (two bound motors). Apparently, bound motor substituent
progressively impede the binding of the viologen guest. The absolute
values of the association constants depend on the N -substituents
of the viologen. We reason that for all isomers of Zn3 the
binding of n -pentyl viologen V6 is more sterically
demanding than the binding of methyl viologen V4 , resulting in
lower K a-values. In contrast, benzyl viologenV5 forms the strongest complexes with all the isomers ofZn3 , which we attribute to the ability of the benzyl functions
of this guest to form additional π-π interactions with the molecular
motor substituents of the host. The binding studies and trends presented
in Table 1 only represent the behavior of the motorized porphyrin cages
in their stable ground states. Isomerization of the molecular motor
substituents to the metastable states results in opposite relative
stereochemistries, and therefore it may also result in different binding
behavior.
TABLE 1 Association constants (Ka in
M−1) and Gibbs free energies (ΔG0 in
kJ/mol, in brackets) for the complexes of the isomers of porphyrin cageZn3 with viologen guests V4 –V6(CHCl3/CH3CN, 1:1, v/v, 298 K).