Full Paper
been accessible so far for POMs, which could result in the for-
mation of new protein crystals promoted by POMs.
Experimental Section
Full experimental data and synthesis procedures can be found in
the Supporting Information. All reagents and chemicals were of an-
alytical grade and used without further purification. All reagents
and chemicals were supplied by Sigma–Aldrich Chemical Company
and solvents were supplied by Merck Chemicals. Single-crystal X-
ray diffraction data were collected at 100 K by using a Bruker D8
Venture diffractometer equipped with a multilayer monochroma-
tor, a MoKa INCOATEC microfocus sealed tube (l=0.71073 ), and
a
CMOS Photon Detector. CCDC 1406885 (TBA-FeMo6-bzn,),
1406886 (TBA-MnMo6-bzn), 1406887 (TBA-FeMo6-cin), and
1406888 (TBA-MnMo6-cin) contain the supplementary crystallo-
graphic data for this paper. These data are provided free of charge
Figure 6. Hypothetical binding of aromatic hybrid POM to HSA. HSA is
shown as a ribbon structure with all subdomains represented in different
colors. Right: The aromatic hybrid POM is depicted with its dimensions. The
red arrow indicates the big cavity that leads to subdomain IIA (in red).
Inset: A closer view of the hypothetical position of the POM together with
IMN, which is located next to fluorophore Trp214. The POM is illustrated as
a combination of polyhedra and sticks, whereas IMN and Trp214 are illustrat-
ed sticks (color code: IMN: carbon=cyan, blue=nitrogen, red=oxygen,
light green=chloride; Trp214: red=carbon, blue=nitrogen).
Synthesis of TBA-FeMo6-bzn,
(TBA)3[FeMo6O18{(OCH2)3CNHCOC6H5}2]·3.5ACN
The synthesis was carried out according to a published proce-
dure.[36] Tetrabutylammonium octamolybdate was dissolved in ace-
tonitrile and heated at reflux with Fe(acac)3 and the ligand
(HOCH2)3CNHCOC6H5 for 18 h. After cooling to RT, the red mixture
was centrifuged to remove the precipitate and give a dark red so-
lution. Crystals suitable for X-ray crystallographic analysis were ob-
tained through ether diffusion after a few days. FTIR: n˜ =2960 (v
CH3, s), 2934 (v CH3, s), 2873 (v CH3, s), 1674 (v C=O, s), 1599 (v Ar,
w) 1578 (v Ar, w), 1517 (v Ar, m), 1482 (d CH2, s), 1380 (d CH3, m),
1319 (m), 1268 (m), 1102 (m), 1031 (v CÀO, m), 939 (s), 918 (s), 902
(v Mo=O, s), 808 (w), 647 (v Mo-O-Mo, s), 559 (m) 406 cmÀ1 (m). El-
emental analysis calcd (%) for FeMo6O26C70H132N5 (2091.3 gmolÀ1):
C 40.20, H 6.31, O 19.41, N 3.26, Fe 2.67, Mo 28.01; found: C 40.19,
H 6.28, O 19.38, N 3.24, Fe 2.61, Mo 27.94.
suggested that the aromatic hybrid POM approaches subdo-
main IIA through the above-mentioned cavity and then exhibit
hydrophobic interactions with its hydrophobic tails, whereas
the Anderson core is stabilized through electrostatic interac-
tions with polar amino acid side chains from, for example, sub-
domain IB (Figure 6). This is not surprising because the organic
moiety of the hybrid POMs are structurally very similar to cin-
namic acid, which has been shown to bind to HSA sub-
domain IIA (together with IMN) by directly interacting with
Trp214.[52] Thus, the aromatic hybrid POMs reported herein
might interact similarly with HSA through their organic groups.
Synthetic procedures for TBA-FeMo6-bzn, TBA-FeMo6-cin, TBA-
MnMo6-bzn, TBA-MnMo6-cin, Na-FeMo6-bzn, Na-FeMo6-cin, Na-
MnMo6-bzn, Na-MnMo6-cin, bzn, and cin, and the full experimen-
tal information are given in the Supporting Information.
Conclusion
Acknowledgements
Four different hybrid organic–inorganic Anderson POMs were
synthesized in an organic solvent and introduced to aqueous
environments through a cation exchange step. They show
robust hydrolytic stability in a pH range of 4 to 9 for up to
24 h and are hydrolytically inactive in aqueous buffer solutions
in the presence of BSA and HSA proteins. Instead, they interact
through electrostatic, hydrophobic, or p–p interactions, or
a combination of these. This introduces the possibility for an-
other mode of POM–protein interaction in addition to the
demonstrated electrostatic interaction. The terminal oxygen
atoms on the Anderson POM can interact electrostatically with
positively charged amino acids. The double-sided grafting of
the aromatic ligands may allow for p–p interactions or hydro-
phobic interactions at two different sites. This makes the
hybrid Anderson POMs reported herein potentially superior to
pure inorganic structures that have been successfully applied
so far as additives in macromolecular crystallography. Thus,
they may in theory stabilize new protein regions that have not
The research was funded by the Austrian Science Fund (FWF):
P27534. The EU COST action PoCheMoN (CM1203) is gratefully
acknowledged. We are grateful to Ing. Peter Unteregger for his
support with the ESI-MS measurements at the Mass Spectrom-
etry Centre, University of Vienna. We also thank AoUniv.-Prof.
Eugen Libowitzky for access to ATR-IR measurements and
AoUniv.-Prof. Dr. Markus Galanski for support with NMR spec-
troscopy measurements. We acknowledge AssUniv.-Prof.
Mag. Dr. Wilfried Kçrner for help with ICP-OES measurements,
Department of Environmental Geosciences, University of
Vienna. Last, the authors wish to thank Dipl.-Ing. Matthias Pret-
zler, Aleksandar Bijelic, M.Sc., and Ioannis Kampatsikas, M.Sc.,
for valuable discussions concerning this work.
Keywords: characterization
·
hydrophobic
effect
·
polyoxometalates · synthesis · X-ray crystallography
Chem. Eur. J. 2015, 21, 17800 – 17807
17806 ꢀ 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim