Angewandte
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Chemie
quaternary structures; thus, we hypothesized they would give
rise to regular nanoscopic shapes (Scheme 1).
Herein, we show that, using TMV as a template, the as-
fabricated TMV@ZIF-8 retained the highly anisotropic rod
shape of the parent virus. We were able to tune the thickness
of the MOF shell by modifying the synthetic conditions. The
as-obtained TMV@ZIF-8 composite demonstrates good sta-
bility in organic solvents and at high temperature. The
surface-exposed tyrosine groups of the TMV remain reactive
while inside the MOF shell and coupling reactions performed
through the MOF do not undermine the integrity of the rod-
shaped hybrids. Most strikingly, even after immersing the
TMV@ZIF-8 in pure methanol overnight, we were able to
remove the ZIF-8 shell and show that the virus itself could be
reclaimed undamaged under these highly denaturing condi-
tions.
For our initial experiments, a desalted virus solution was
mixed with an aqueous solution of HMIM. Upon addition of
an aliquot of Zn(OAc)2 the reaction mixture immediately
became turbid followed by flocculate formation. After
16 hours, the centrifuged solid was washed with ultrapure
water twice to obtain an off-white suspension in water. We
were initially pleased to find the anticipated rod structures by
SEM but then frustrated to discover that the rods were very
unstable; when removed from the mother liquor solution
containing Zn and HMIM and placed in deionized (DI) water
they collapsed into flaky cubes overnight (Supporting Infor-
mation, Figure S1b). From powder X-ray diffraction (PXRD)
analysis of the as-synthesized rods, we observed that the shells
contained the expected ZIF-8, but also reflections corre-
sponding to a significant amount of crystalline Zn(OAc)2
were observed (Supporting Information, Figure S2). This led
us to conduct an investigation into the optimization of our
synthetic conditions to reduce unwanted Zn(OAc)2 growth
and improve the stability of our rod composites. As a result of
this investigation, we found that we could greatly affect not
only the physical stability of the composites but also the shell
thickness. A key observation was that when the HMIM:Zn
molar ratio was low, the TMV@ZIF-8 core–shell composites
had thinner shells and, conversely, at higher HMIM:Zn ratios,
the shells thickened.
Two representative products of this investigation are
presented in Figure 1, denoted as TZ-thin (micrographs
shown in Figure 1a and b) and TZ-thick (Figure 1c and d).
Synthetically, these two composites are differentiated by the
HMIM:Zn molar ratio used in their preparation. Specifically,
the TZ-thin composite was prepared from a 20:1 ratio and the
thicker wall of TZ-thick was obtained when that ratio was
increased to 40:1. SEM analysis shows that both composites
form regular and homogenous rods with very tightly con-
trolled thickness. TZ-thin, for instance, is 70 nm in diameter
and TZ-thick is 100 nm. We could control the surface coating
of the TMV@ZIF-8 as well by changing the concentration
used in drop casting. The dense forests shown in the SEM
images are a result of drop casting at high concentrations.
Furthermore, we could isolate more discrete rods, even single
rods, at lower concentrations (see the Supporting Informa-
tion, Figure S3 and Figure 1 high magnification insets). TEM
shows the viral interior, which arises from the low-contrast
Figure 1. a) SEM and b) TEM of as-synthesized TZ-thin. c) SEM and d)
TEM of as-synthesized TZ-thick. Inset scale bar: a), c) 200 nm; b),
d) 50 nm.
TMV rod residing within the shell (Figure 1b and d). This
provides direct evidence of successful ZIF-8 encapsulation of
the tubular virus particle. We also observed rods much longer
than 300 nm by SEM and TEM. This arises from TMVꢀs
propensity to align head-to-tail.[16a,d] This phenomenon is
illustrated in the inset of Figure 1d, which shows one of these
supramolecular junctions in which the virus particles line up
in a head-to-tail fashion.
Crystallinity was confirmed by PXRD analysis showing
reflections in excellent agreement with the simulated ZIF-8
pattern (Figure 2a). Thermogravimetric analysis (Figure 2b)
under an air atmosphere shows a two-stage weight loss in both
TZ-thin and TZ-thick, from 250 to 3508C, which we
attributed to the decomposition of the proteins, then
a sharp decrease at 4508C consistent with the decomposition
of pure ZIF-8. The permanent porosity of the resulting shell
was confirmed by nitrogen absorption analysis at 77 K
(Figure 2c). The final BET surface-area values of the separate
composites show an expected decrease in available surface
area associated with the incorporation of the virus. The
solution stability and synthetic yield were analyzed by
functionalizing the inner channel of the TMV with a fluores-
cent FITC tag (fTMV, see the Supporting Information) and
then growing the ZIF-8 shell around the resulting virus. After
the growth and centrifugation of the composite, we found
nearly undetectable levels of fluorescence remaining in the
growth solution (Figure 2d, inset 1), indicating a nearly
quantitative capture of fTMV. To determine if TMV could
escape from the ZIF-8 and re-enter the solution, we
monitored the fluorescence of a fTMV@ZIF-8 solution
(Figure 2d, inset 2) over 24 h. As shown in Figure 2d the
fluorescence did not increase until the shell was removed by
2
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Angew. Chem. Int. Ed. 2016, 55, 1 – 7
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