Achiral endohedral functionality provides stereochemical control in Fe(ii)-based self-assemblies

Article abstract of DOI:10.1039/c3cc37912d

Multicomponent Fe(ii)-iminopyridine-based self-assemblies have been synthesized with variably sized internal functionality. Larger internal functions provide increased strain to the complex and confer diastereocontrol upon the assembly process. Complete d

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Achiral Endohedral Functionality Provides Stereochemical Control in
Fe(II)-Based Self-Assemblies
Michael C. Young, Amber M. Johnson, Ana S. Gamboa and Richard J. Hooley*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
coordinating ligands.13 An alternative strategy is to control
Multicomponent Fe(II)-iminopyridine-based self-assemblies
assembly by suitably functionalizing the cage interior. Relatively
40 little attention has been paid to the inclusion of introverted
functionality into selfꢀassembled cage complexes.14 Here we
show that stereochemical information at different metal centers in
a selfꢀassembled cage can be regulated by the incorporation of
suitably sized achiral substituents on the interior.
have been synthesized with variably sized internal
functionality. Larger internal functions provide increased
strain to the complex and confer diastereocontrol upon the
10 assembly process. Complete diastereocontrol is possible upon
the introduction of large achiral groups on the cavity interior.
45
Controlled introversion of functionality in a metalꢀligand cage
complex requires the correct ligand structure to both form a
defined selfꢀassembly and to prevent extroversion of the desired
functional group. In addition, a suitable metalꢀcoordinating motif
must be incorporated. Vꢀshaped bisꢀaniline preꢀligands such as
Reversible metalꢀligand interactions have been exploited for the
selfꢀassembly of a variety of structural motifs into larger
aggregates.1 These can take the form of coordination polymers,2
15 2ꢀdimensional polygons,3 or 3ꢀdimensional polyhedra.4 This
strategy for making large synthetic structures relies on the
reversibility of dative bond formation, allowing for equilibration
to the most thermodynamically favored product.5 Assembly can
occur via multiple ligands with monodentate coordinators6 or
20 multidentate coordinators.7 The assembly of multiple bidentate
50 those shown in Fig. 1 allow both controlled selfꢀassembly and
forced introversion of desired functional groups. When
condensed with 2ꢀpyridinecarboxaldehyde, it is expected that
they will form iminopyridine ligands 1ꢀ6 (Fig. 2) which will lead
to the formation of Fe2L3 helical assemblies with Fe(II) salts.15
ligands around
a
metal introduces the possibility of
stereoisomerism. Controlling the stereochemistry at the metal
center is vital for analysis, especially polynuclear assemblies.8
While some spectacular examples of metalꢀligand cage
25 complexes with diastereocontrol are known,9 this is a generally
unsolved problem. As the ligands become more flexible or longer
causing the distance between the metals to increase, the
stereochemical control decreases, leading to multiple
stereoisomers in the metalꢀligand assembly.10
55 Fig. 2 In situ synthesis of complexes (1-6)3·Fe2·(ClO4)4.
The synthesis of the ligands is convergent and modular, allowing
simple access from substituted 2,6ꢀdihalobenzene derivatives, and
a number of differentlyꢀsized groups can be introduced to the
interior of the system. Ligand 7 was used as a control system, to
60 illustrate the differences in stereochemical control as the distance
between the metal centers is reduced.16 Six preꢀligands were
targeted for the study: unfunctionalized ligand A, aniline B and
nitroꢀaniline C all have small internalized groups that can be
incorporated on the interior of an Fe2L3 helix with no steric
65 penalty. The effect of larger functional groups can be studied via
benzyl ether derivatives D and E, which will provide steric
hindrance to the assembly. These larger benzyl ether derivatives
D and E cannot reasonably form an Fe2L3 helix with all three
benzyls oriented directly towards the cavity, but are flexible
70 enough to be incorporated in the assembly. Adamantanide F is
too large and rigid for internalization and serves as a control. Full
synthetic experimental details can be found in the ESI.
30 Fig. 1 Precursor Ligands A-F and Ligand 7.
Finding new strategies for stereocontrol in the formation of
selfꢀassemblies with octahedral metals and bidentate ligands will
allow a far greater range of functionalized selfꢀassembled cage
species to be controllably formed, and allow further applications
35 in selective molecular recognition and biomimetic catalysis.11
Methods to control metalꢀbased stereochemistry in larger cages
vary from guest templating effects12 to the use of homochiral
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Metalꢀiminopyridine complexes can be prepared by 30 tetrahedra, ESIꢀMS analysis of the smaller complexes (1-3)x·Fey
combination of ligand and metal or by reacting the aniline,
aldehyde, and metal in situ.18 As the addition of metal promotes
the imine condensation, even in aqueous media, we found the
oneꢀstep procedure produced a better overall yield.19 Preꢀligands
confirmed the presence of the entropically favored (1-
3)3·Fe2·(ClO4)4 helices. The instability of the complexes caused
significant fragmentation, but isotope patterns for the observed
M+ ions of (1-3)3·Fe2·(ClO4)4 were consistent with the presence
5
A-E were each added to a rigorously degassed acetonitrile 35 of two Fe atoms (Figure 3e and ESI). Larger adducts (e.g. M3L4
solution containing 2ꢀformylpyridine and Fe(ClO4)2, immediately
causing the solution to turn an intense purple color, indicative of
the formation of a low spin Fe(II) iminopyridine complex.20 The
for ligand 1) are observed in small amounts in the ESIꢀMS, but
are not coordinately saturated by the iminopyridine ligands, and
1
cannot be stable solutionꢀphase assemblies. When studied by H
10 (1-5)3·Fe2·(ClO4)4 complexes were isolated as purple solids via
NMR spectroscopy, the complexes (1-3)3·Fe2·(ClO4)4 all showed
precipitation with ether. Despite having introverted aniline 40 two discrete sets of resonances in the 1H NMR spectrum. The two
functionality, there was no competition with the exterior anilines
for imine formation during synthesis of 23·Fe2 and 33·Fe2, even in
the presence of excess aldehyde. The smaller 73·Fe2·(ClO4)4
15 complex was accessed via this method and by combination of
sets of peaks for (1-3)3·Fe2 are due to a mismatch between the
homotopic ꢁꢁ/ΛΛ species and the mesotopic Λꢁ species (Figure
3c, 3d).20 Previous work with linear iminopyridine ligands has
shown that typically the less symmetrical mismatched species are
preformed 7 and Fe(ClO4)2. The (1-5)3·Fe2·(ClO4)4 complexes 45 disfavored, and therefore exist as a lower percentage of the
were stable, but displayed strong sensitivity to both air and
moisture, and we were unable to access XꢀRay quality single
crystals for the cages. The assemblies were characterized by H
equilibrium mixture (this principle was applied to the assignment
in Figure 4).8 In contrast, only a single species is observed in the
1H NMR spectrum of the small complex 73·Fe2·(ClO4)4. The
peaks from proton H6 (Figure 3a,b) are diagnostic for the
50 formation of the selfꢀassembled system: the tightly packed
arrangement of the iminopyridines around the iron causes this
proton to be shielded, giving an upfield ꢁδ of approximately 1.8
ppm. The known structure of this complex is the homotopic
ꢁꢁ/ΛΛ isomer, and the mesocate is not observed in solution.16
1
20 NMR, 2DꢀNMR, Diffusion NMR and ESIꢀMS.
55
Integration of the individual resonances for (1-2)3·Fe2·(ClO4)4
allows determination of the relative amount of each isomer. The
proportions of the two species were dependent on the introverted
functional group: while both complexes 13·Fe2 and 23·Fe2
displayed ~2:1 ratio between homotopic ꢁꢁ/ΛΛ and mesotopic
60 Λꢁ species, a higher proportion of the second species was
observed for nitroaniline complex 33·Fe2. In this case, selfꢀ
assembly gave a nearly equal mixture of both the ꢁꢁ/ΛΛ and Λꢁ
species. DOSYꢀNMR analysis of the (1-2)3·Fe2·(ClO4)4
complexes showed (within error) no difference in diffusion
65 coefficient between the two diastereomeric species. In CD3CN
solution, the diffusion coefficient for 23·Fe2·(ClO4)4 was 5.3 x 10ꢀ
10
m2/s. The reasons for the stereoselectivity (or lack of it) in
formation of the Fe2L3 species lie in the flexibility of the ligands.
The small 73·Fe2·(ClO4)4 assembly has a high level of strain
70 around each metal center.8,20 The lowest energy isomer is that of
the homotopic ꢁꢁ/ΛΛ assembly; the significant strain generated
upon assembly of the small ligand 7 disfavors formation of the
mismatched mesotopic isomer. The longer, more flexible ligands
1-3 do not generate significant strain upon selfꢀassembly. When
75 the organic ligand becomes large enough (such as in
13·Fe2·(ClO4)4), there is additional freedom to "flex" the ligand
orientation around the metal. This allows the mismatched
mesotopic species to form, as has been observed in iron(II)ꢀ
iminopyridine selfꢀassemblies with long linear ligands.9
Fig. 3 a) 1H NMR spectra (CD3CN, 500 MHz, 298K) of the complex
33·Fe2·(ClO4)4; b) of the complex 73·Fe2·(ClO4)4; c) minimized structure
of ΛΛ 13·Fe2 (SPARTAN); d) minimized structure of Λꢁ 13·Fe2
(SPARTAN); e) Predicted and observed ESIꢀMS spectra of M2L3
25 complex [13·Fe2·(ClO4)4+2H]2+.
80
Preꢀligands A, B, and C all display small functions on the cage
interior and these species are unable to provide any extra strain,
so do not bias the formation of the homotopic assembly. The
larger groups on preꢀligands D and E, however, can provide extra
steric hindrance to the assembly. Molecular modeling shows that
The initial comparison was performed between the "small"
introverted species (1-3)3·Fe2·(ClO4)4 and the tightly packed
complex 73·Fe2·(ClO4)4. While the geometry of the ligands may
theoretically allow formation of larger aggregates such as Fe4L6
85 the cavity of 43·Fe2·(ClO4)4 is crowded but the flexible benzyl
groups are able to rotate and allow formation of the
corresponding Fe2L3 cage, albeit with extra steric strain. Indeed,
2
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when 43·Fe2·(ClO4)4 is formed as before, diffusion NMR and
ligand flexibility becomes limited, precluding the formation of
ESIꢀMS confirmed the presence of the Fe2L3 complex. While 40 the mismatched mesocate isomer. Further experiments on the
larger M4L6 adducts are observed for ligand 4 in small amounts in
the ESIꢀMS, they are not observed in solution. In this case, only
one set of peaks is observed in the 1H NMR spectrum, indicating
that only one diastereomer (the more favorable matched ꢁꢁ/ΛΛ
complex) is formed. The absence of the mesotopic assembly can
be explained by strain.8,13 The presence of large achiral groups on
the interior of the cage increases the strain upon complexation
control of assembly via internal functionalization are underway.
5
Notes and references
Department of Chemistry, University of California – Riverside,
Riverside, California 92521, USA. E-mail: richard.hooley@ucr.edu;
45 Tel: +1 951-827-4924
† Electronic Supplementary Information (ESI) available: Full
experimentals
and
NMR/ESIꢀMS
characterization.
See
10 and disfavors the mesocate (see ESI).
DOI: 10.1039/b000000x/
The effect of the internal functionality on the selectivity of
assembly can be tested by increasing the size of the internal
groups. Ligand 5 displays larger internal functions than 4, but
those groups can still move into the "gaps" between ligands. If
15 the benzyl groups in 43·Fe2·(ClO4)4 are flexible, the addition of a
bulky tꢀbutyl group (as in preligand E) should have relatively
little effect, and the Fe2L3 helix should still form. If the groups
are not able to point outside of the capsule, then the Fe2L3 would
be disfavored, likely giving rise to a coordination polymer.
20 Characterization by 1HꢀNMR and ESIꢀMS confirmed that E
formed a single diastereomer of 53·Fe2·(ClO4)4 (Figure 4d). As
might be expected, 53·Fe2·(ClO4)4 also selected for the homotopic
assembly, as only one set of peaks were observed. Larger, more
rigid preligand F is incapable of motion to allow assembly: no
25 discrete 63·Fe2·(ClO4)4 complexes are formed from preligand F,
only a mostly insoluble coordination polymer.
†† The authors wish to thank Dr. Dan Borchardt and Prof. Cynthia Larive
50 for assistance with DOSYꢀNMR, Ron New for mass spectral analysis and
the National Science Foundation (CHEꢀ1151773) for research support.
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Fig. 4 Stereoselective Assembly: a) minimized structure of the observed
53·Fe2 homotopic isomer (SPARTAN). Labeled NMR Spectra (CD3CN,
400 MHz, 298K) of b) 23·Fe2·(ClO4)4; c) 33·Fe2·(ClO4)4; d)
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to homotopic assemblies, red dots correspond to the mesotopic species.
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In conclusion, we have reported the synthesis of internally
functionalized Vꢀshaped iminopyridine ligands and their
multicomponent selfꢀassembly properties in the presence of
35 Fe(II) salts. Increased ligand rigidity generally favors
stereocontrol in Fe(II)ꢀiminopyridine clusters, and this can be
exploited by applying steric strain to the interior of the cavity.
As bulky groups are added to the interior of these cages, the
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