C O M M U N I C A T I O N S
4
contained an active, moisture-sensitive group. Using high-
resolution FAB-MS, we determined the molecular formula of 4 to
Si (Figure S3). The MS analysis of a mixture of
Glu-NCA and HMDS (5:1 molar ratio) showed peaks of 644 and
63 Da (Figure 4S) that corresponded to the dimer and trimer of
be C19H
33
O N
5 2
2
8
Glu peptides, respectively, with identical TMS-CBM terminal
groups as 4.
From these studies, it is evident that polypeptide chains were
propagated through the transfer of the TMS group from the terminal
TMS-CBM to the incoming monomer to form a new TMS-CBM
terminal propagating group (4 to 5, Figure 2A). To demonstrate
that controlled NCA polymerizations were mediated by a TMS-
CBM group, we tested Glu-NCA polymerizations using trimeth-
ylsilyl dimethylcarbamate (TMSDC) as the initiator. As expected,
polymerizations proceeded smoothly to yield PBLGs with antici-
pated MWs and narrow MWDs (entries 8 and 9, Table 1).
These HMDS-mediated NCA polymerizations resemble to some
extent the group transfer polymerizations (GTPs) of acrylic
1
5
monomers initiated by similar organosilicon compounds. Unlike
GTPs that typically require Lewis acid activators or nucleophilic
catalysts to facilitate the polymerization,16 HMDS-mediated NCA
polymerizations do not require any additional catalysts or activators.
However, it is unclear whether the TMS transfer proceeds through
an anionic process as GTP16 or through a concerted process
tentatively illustrated as 5 (Figure 2A).
In conclusion, we discovered an unusual TMS-CBM propagating
group that can control the living polymerization of NCAs. This
organosilicon reagent mediated NCA polymerization offers a metal-
free strategy for the convenient synthesis of homo- or block
polypeptides with predictable MWs and narrow MWDs.
Figure 2. (A) HMDS-mediated NCA polymerization through TMS
carbamate group. (B) FAB-MS spectrum of the reaction mixture of equal
molar amounts of HMDS and Glu-NCA.
capability of controlling NCA polymerization should be related to
its TMS group.
As a secondary amine, HMDS can either function as nucleophile
to open the NCA ring at CO-5 or behave like a base to deprotonate
the NH-3 proton (Scheme 1).11 Previous studies showed that
secondary amines with bulky alkyl groups (e.g., diisopropylamine)
exclusively deprotonated NCAs.13 Therefore, it was unlikely that
HMDS, a secondary amine containing two bulky TMS groups,
attacked the CO-5 of Glu-NCA (Scheme 1). If the first step involved
the deprotonation of the NH-3 proton of NCA by HMDS, an
N-TMS NCA would form and should undergo rapid rearrangement
Acknowledgment. We acknowledge the support from the
University of Illinois at UrbanasChampaign (UIUC), the American
Chemical Society Petroleum Research Fund, and the Center for
Nanoscale Science and Technology at UIUC, and the Siteman
Center for Cancer Nanotechnology Excellence.
Supporting Information Available: Experimental procedures and
the FT-IR, MS, and NMR of HMDS-mediated polymerizations. This
material is available free of charge via the Internet at http://pubs.acs.org.
14
to form R-isocyanatocarboxylic acid TMS esters. However, no
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1
isocyanate peak (∼2230-2270 cm ) was observed when the
(
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2
D O was added to 4, only 4c (Figure 2A) was detected (by FAB-
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