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a-Sheet Peptide Architecture Measuring the Relative Stability of Parallel vs. Antiparallel -Sheets

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__
fold rotation axis parallel to the i~ axis passing through the
center ofthe peptide ring (Fig. 2a). Two peptide subunits ( I ) are
closcl) stacked in an antiparallel orientation and are related by
a tnol'old rotation along either the N or h axis (Fig. 2b). The
/i-s h eet - I i k e c y l i nd r ica I en scm ble i
bilized by eight intersubunit li~drogen-bondinginteractio
ith an intersubunit N - 0
distance of 2.90 A. The distance of 3.95 A inferred from the
observed N H stretching band at 3312 c m - ' in the FT-IR spectrum i\ remarkably consistent with the crystallographic measureincnts. 7 he cylindrical dimer has an approximate !an der
Waals internal diameter of 7.5 8, and a volume of 450 A 3 . The
tubular cavity is tilled with partially disordered water molecules.
establishing the hydrophilic internal characteristics of the peptide nanotube structures (Fig. 2). The diiner packs in the crystal
in 21 body-centered fashion to produce ;I continuously channeled
superlattice along the c ' axis (Fig. 2c and d ) . The interior surface
characteristics of the channels alternate approximately every
I 1 bctwccii tlic hydrophobic domains. created by the aromatic phcnyl moieties itnd the hydrophilic interior of the peptide
dimer. Water molecules near the hydrophobic domains are considerably inore disordered. displaying only a weak residual electron density. Thc obscrvcd clcctron density for water is the
tinwaverage 01' water molecules binding at several overlapping
sites. which wggests ii facile inovement of loosely held water
molecules within the cavity. This observation. which can be
attributed t o the lack o f a discrete. strong binding site (or sites),
is ;ti1 imp~~rtitiit
attribute of thc pcptide nanotube structures and
may bc useful for rationalizing the remarkable transport efficiencies 01' the recently described transmembrane ion channels.["I
The design principle described above is expected to have a
number 01' potential applications. Appropriately designed subunits with h!drogcn bonding possible only in one direction can
be used ;IS tube terminators or capping agents and may be used
t o gate tho sell'-assciiibled transmembrane ion channel strucique amphiphilicity of the noncentrosyminetric
xils may be useful for binding both hydrophobic
ic substrates. thus extending the potential utility
of peptide nanotubes as inolecular inclusion devices and nonlincar opt ica I materials.
Rcceiced: July X. I994 [Z 7113 IE]
(ici-iiiw
Keywords: nanostructures
*
versioii: .4ii,yi\
peptides
*
Climi. 1995. 107. 76
self-assembly
M . R . Ghadiri, J. R . Graiiju. I-. K . Buehler.
304.
1994. 369. 301-
Vii[iire (/,oiidoiij
N. Kh;i/aiiovich. J. R Ciranja. D. E . McRee. R A
ill. c ~so(..
~1994.
( i i o~. m ~i 6012.
~ ~
S. Iilima. ,V(i/irre (Lomkiii) 1991. 354. 56 ~ 5 8 .
J. M Schnur. S c i n w ~1993. 262. 1669 1676.
MiIIi~.iii.
M.R Ghadiri, J ,
J.-H. Fuhrhop, D. Spiroski. c'. Boettcher. .I h i .C'liwii 5~ 1993. 11.5, lh00
1601.
A. Harada. J. Li. M. Kamachi, *V(ifiirc(Loiidoii) 1993. 3h-l. 516 51X
C . T. Kresge. M . E. LeonowicL, W. J. Roth, J. C'. Vartuli. J. S. Heck. ,Vri/irrc
( L o i i h i i ) 1992. .iiY. 710 712.
M . E M . Roks. R. J. M . Nolte. , ~ [ ~ [ , r f i i i i o / i ~ i1992.
i ~ l ~ ,25.
\ 539X 5407.
0. S. Huo. D I . MMnrgolese. U . Ciesla. P. Feng. T. E.Gici-. P. Sieger. R.Leon.
P. M . Petroff. F Schuth. G D . Stuck!. ,Vu/iirc (Loiidoii) 1994. 368.
The liiiciir form of the tnrget sequene H( i.-Phe-i~-.2"-~~c-.41nla(
synthesized nccording to \tandard solid-phare method\ a i d then ckclized in
solution t o furnish the desired cyclic peptide subunit
d u r e : A solutioii o f t h e linear peptide in D M F ( I inM
benrotri;iLol-l-yl)-I
. I .3.3-tetrametliyluroniuiii hexo
I -hydroxq benzotriamle (3 mM). and diisopropyleth
for 12 h t o give the desired cyclic pcptidc in 70% yicld iiHcr rc\crsc-phase
HPLC pui-itication
A Bax. D G . Daws, .I 111u~ii./?<,..\on.1985, h i . 2137 21.7
ROESY experiments were performed o n :I Bruker AMX-500 with 300 ins \pin
lock (mixing) tiine using Bruker's standard pulse progruii. Data were procesied m i t h FELIX software. Time domain data was apodiicd w i t h skewed ainehell squared w i n d o u functions. Zero-lilling w i i h used to (ihtain thc linal data
\i/e o f the 1013 x 1024 complex inatrix.
The iisociiitioii c o n m n t s reported are the lo\rer limit\ hccaii\e of t h e preaence
of siniill ainouiits of included u a t e r iii the peptide w i i p l e \ . When water is
I-igorouzly excluded ( 4
inoleculiir sieves) the :i\wciiition
K,,(CDCI,) = l 2 6 O W 1 is approximately doubled to k,iC'DCI,) = 2
The v;rlui. of K,(CCI,) reported w;is meawred i n ;I mixtiire ofX4'X1 (
16"t CDCI, for re'isoiia of solubilit).
Data \bere collected on a Rigaku AFC'6R diffr;ictometi.r q u i p p e d with ii
rotating copper anode (Cu,,) and a highly oriented graphite iiiOnOc1irom;itOr.
The structure \\as solved i n the space group I422 with ii lin;il K tictor of8.X7%,
neighted R factor of 1 0 35%. and residual electron denhily of 0.64 e A ~for
9 x 3 unique retlections with I.'> 4.0o(F). The uiiit ~ x l l par;iiiieters arc
= h = 16.7X. a n d c = 21.97 A.
A
91
P-Sheet Peptide Architecture:
Measuring the Relative Stability of
Parallel vs. Antiparallel P-Sheets""
Kenji Kobayashi. Juan R. Granja, and M . Reza
Ghadiri*
It1 t i i w i o r j ' o f ' Prqfi..c.sor Lirztis
C. Pu~ilitig
Among the most commonly occurring protein secondary
structures, /&sheets are the least studied because well-characterized peptide model systems are not available.['
In particular,
despite a number of theoretical studies implicating the possible
role of amino acid residues and cross-strand interactions between side chains in directing the folding characteristics of psheet structures,'"' to date no direct experimental evidence has
been forthcoming to establish the underlying energetic factors
[*I Prof. M. R . Ghadiri. Dr
K. Kobayashi. Dr. J. R . Criinj<i
Departments of Chemistry a n d Molecular Biology
lhe Scripps Research Institute
10666 North Torrc) Pines Rotid. La Jolla. CA 92307 ( U S A )
TeleI"ix. I n t . code (619i554-6656
+
[**I
This m u r k w a s supported in part by the U.S. Oflicc ol'iV,iial Research and the
Nation;il Institute of Genertil Medicine. We thank collo:igiiea 11. H. 1-1ii:ing a n d
M . A.Case for their assistance in N M R spectroscopy K . K . acknouledges the
Ministry of Education. Science. and Culture of J a p a n foi- ii postdoctoral fellowship. J. R. <;. thanks NSCORT for a xiiiimer lello\\ahip. M . R. G. 1 5 ii
Scarle Scholar (1991 -1994) and Alfred P. Sloan Re\c.irch Fellou (1993
1995)
95
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that may favor the formation of parallel or antiparallel arrangements. Here we describe the design, synthesis, and characterization of a novel model structure for 8-sheets and provide the first
direct evaluation of the thermodynamic preference for the antiparallel vs. parallel 8-sheet formation. Within the constraints
of the present model, our studies establish for the first time the
significant role of backbone- backbone hydrogen-bonding interactions in favoring the formation of the antiparallel /$sheet
structure.
The de novo design of peptides with well-defined 8-sheet
structures has been hampered primarily by the propensity of
extended hydrophobic or amphiphilic polypeptides toward nonspecific intermolecular aggregation, by lack of control over the
relative sheet register, and by the inability to predict or control
the extent of the backbone twist in such structures.[51Moreover,
there has been no study to date that documents the formation of
parallel and antiparallel /?-sheet structures starting with the
same o r similar peptide sequence(s), which might allow direct
assessment of the role of backbone-backbone interactions and
cross-strand interactions between side chains in such arrangements. In the preceding article, we described the design of an
antiparallel /I-sheet cylindrical ensemble based on the selfassembly of flat ring-shaped cyclic peptide subunits with a
specifically N-methylated backbone.[61 This unique /]-sheet
ensemble is free of the complications commonly plaguing 8sheet model systems and constitutes the basis structure for the
present study.
The cyclic octapeptides 1-3 were designed for the task in
hand. They all share the following basic design principles: The
peptides are made up of eight alternating D- and L-amino acids
which adopt a flat ring-shaped conformation in nonpolar organic solvents and stack to form cylindrical 8-sheet arrangementsL6.'] Solution-phase ' H N M R studies as well as highresolution X-ray structural analysis have indicated that all backbone 4 and $ dihedral angles reside within the accessible 8-sheet
regions of the Ramachandran map.r81The present design satisfies the two criteria essential for directing the formation of parallel and/or antiparallel @-sheetensembles. It provides absolute
control over the facial selectivity of the strand in intermolecular
hydrogen-bonding interactions between the backbones and the
means of rigorously regulating the relative sheet register thereby
setting the identity of the cross-strand nearest neighbor residues.
The facial selectivity is directed by the N-methylated amide
functionalities of the backbone, which prevent one face of the
peptide ring structure from participating in intermolecular hydrogen bonding. Control over the sheet register is the direct
consequence of the alternating D- and L-conformations of the
backbone, which constrains the 8-sheet structure so that only
homochiral residues can make up the cross-strand 8-sheet neare
pairs. This restriction is engendered by the requirement for the
intermolecular hydrogen-bonding pattern which is dictated by
the juxtaposition of amide hydrogen-bond donor and acceptor
sites, as well as by the large steric interactions between side chain
and backbone in alternative sheet-register and side-chain arrangements. Therefore, as the result of the above design features, enantiomerically pure peptides such as 1-3 can only form
homodimeric antiparallel 8-sheet structures. However, the same
structural reasoning would dictate that a /3-sheet structure made
up of two enantiomeric peptide subunits must necessarily form
the corresponding heterodimeric parallel 8-sheet arrangement.
With this basic design notion in hand, we set out to measure
the relative stability of parallel vs. antiparallel 8-sheet structures
using the two enantiomeric forms of the same peptide sequence
(peptides 1 and 2). A racemic solution containing an equal
amount of peptides 1 and 2 can produce an equilibrium mixture
of the parallel ensemble 1 . 2 and the enantiomeric antiparallel
1 . 1 and 2 . 2 /j-sheet structures (Scheme 1). Formation of
diastereomeric 1 . 2 and 1 . 1 (or its enantiomer 2 . 2) complexes
can be conveniently monitored by 'H N M R spectroscopy. Previously, we have shown that peptide 1 o r 2 can self-assemble in
nonpolar organic solvents to form the predicted antiparallel
8-sheet structure.[6]The structural and thermodynamic characteristics of the 8-sheet structure have been established with highresolution X-ray crystallography and I D and 2D 'H N M R
spectroscopy. A particularly diagnostic feature in the ' H N M R
spectrum of peptide 1 o r 2, which signifies formation of the
antiparallel @-sheet structure, is the resonance for the intermolecularly hydrogen-bonded N H proton at 6 = 8.73 having a
Scheme 1. The strategy employed for measuring the relative stability of the parallel and
antiparallel fi-sheet structures
is schematically illustrated.
For simplicity. only the backbone structures of the ensembles are illustrated (D and L
refer to the chirality of the
amino acid residues). Note
that in all threeensembles only
homochiral residues make up
the nearest neighbor crossstrand pairs as indicated by the
partial labeling of the rH, positions. Association constants
(K,,)were measured directly by
analyzing the 'H N M R spectra (61.
96
8
VCH V~rlo~syesi~lbchrrfi
m h H , 0-69451 W[+dirim. I Y Y S
0570-0X33i95/0101-UU~63 10.00
+ .25:0
Anyew. Clwn. h t . Ed. Enyl. 1995, 34, N o . 1
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J,,,,.,, coupling constant of 8.8 Hz (the NH proton of the free
peptide subunit resonates at 6 = 6.98 with JNH,="
= 7.5 Hz)
(Fig. 1 a). However, an equal mixture of the enantiomeric peptides 1 and 2. in addition to the previously assigned 'H N M R
peaks for the antiparallel structure (1 . I and 2 2), displays a
new set of ' H N M R resonances for the parallel structure
( I . 2).['' The NH proton's signal for the parallel 8-sheet structure appears at 6 = 8.49 with the JNH,zH
coupling constant of
8.8 Hz signifying the similarity of the backbone conformation in
both parallel and antiparallel 8-sheet structures (Fig. 1 b). The
3
....Ala
b
O
1.2
J
3b
3a
-6
Fig. 1 . The N H ugnals of the ' H N M R spectrum (500MHz in CDCI, at 293 K) of
a) enantiomerically pure peptides I or 2 (1 mM), b) a racemic mixture of peptides I
and 2 (10 mMJ. and c ) peptide 3 (3.0mki). All resonances were assigned based on the
analysis of the ROESY spectra 161. The labels refer to the position of the N H
resonances: h ( l ) = f ( 2 ) = 6.98, S(3) = 6.92: 6 ( 1 . 1) = 6(2' 2) = 8.73: 6(3a) =
8.4X and 8.83.and d(3b) = 8.65 and 8.80: 6(1 . 2) = 8.49.All [{-sheet ensembles
display JNlr coupling constants of 8.8 Hz.
1,,
relative intensity of the 'H NMR resonances was used to assess
the free energy of stabilization of the two b-sheet arrangements.
The above studies indicate that the antiparallel 8-sheet structure
(AGZq3= 4.56 kcalmol-', K,(CDCI,) = 2540 M-' at 293 K)'6J
is more stable by 0.8 kcalmol-' than the parallel arrangment
(AG,,, = 3.76 kcalmol-'. K,(CDCl,) = 640 M - ' at 293 K).
An important consideration is whether the measured stability
difference between the parallel and the antiparallel fi-sheet
structures is due to the difference in the backbone-backbone
hydrogen-bonding pattern, or whether there exists a significant
energetic contribution from the cross-strand side chain-side
chain interaction^,[^] which may favor a particular b-sheet
arrangement. Peptide 3 was designed to probe the origin of the
observed structural selectivity. In addition to the phenylalanine
and alanine residues, the peptide contains two leucine residues
in order to exaggerate any existing cross-strand interactions
between side chains. The peptide subunit 3, unlike peptides 1
and 2 which are fourfold symmetric, has only a twofold symmetry along the axis perpendicular to the plane of the ring structure.""] Therefore, two diastereomeric antiparallel P-sheet
ensembles can be formed : in one isomer (3 a) D-Ala . . . D - A I ~ ,
L-Leu . . L-Leu. and L-Phe . . L-Phe residues form the crossstrand pairs. while in the other isomer (3b) D-Ala . . ' D-Ala, and
L-Leu . . . L-Phe residues make up the nearest neighbor pairs
(Fig. 2). If significant cross-strand interactions between side
chains exist. then formation of one ensemble should predominate."O' Analysis of the 'H N M R spectrum of the peptide 3 is
Angrii.. C'lrcwi. In/.
ELI. Enpl. 1995,34, N o . I
P
k
Scheme 2.Schematic representation ofthe self-assembly of peptide 3 producing two
diastereomeric antiparallel b-sheet ensembles 3 a and 3 b (amino acid side-chain
positions in the top strand are indicated by the solid lines and the bottom strand by
the dashed lines). Boxed residues emphasize the differences between the two &sheet
ensembles 3a and 3 b in the juxtapositioning of cross-strand nearest neighbor side
chains.
indicative of an almost equal mixture of the two expected 3a and
3b isomers (Fig. 1 c).I1ll This study clearly establishes lack of
any significant contribution ( 50 cal mol- ' at 293 K) from interactions between side chains toward structural stability, which
is the expected outcome considering the hydrophobic side
chains and the nonpolar solvents employed in the above studies.
Therefore, the observed thermodynamic preference for the antiparallel structure reflects the underlying differences in the
recognition of the backbone-backbone pattern in the parallel
vs. antiparallel /?-sheet arrangements.
In summary, the present study provides the first rigorously
characterized model for 8-sheet structure that assesses the contribution of backbone-backbone interactions and cross-strand
interactions between side chains in directing the formation of
parallel and antiparallel 8-sheet arrangements. It should be expected that changes in the polarity of the medium may produce
significant and additive energetic contributions, emanating
from cross-strand interactions between side chains, toward stabilizing a particular b-sheet arrangement. The availability of the
simple fi-sheet model system presented here may now provide
the means for the detailed characterization of underlying factors
which favor the 8-sheet structural fold.
-
Received: September 5. 1994 ( Z 7292 IE]
German version: Angrw. Chivn. 1995. 107, 79
Keywords: peptides self-assembly * 8-sheet structures
[ l ] a) L. Pauling, R. B. Corey, Proc. Narl. Acud. Aci. G S A 1951,37, 251 256: b)
;hid. 1953,39,253-256;c) F.R. Salemme, Prop. Biophya. mole^,. Bid. 1983,42.
95-133.
[2] a) C . A. Kim, J. M. Berg, Nuturc (London) 1993. 362. 267 270; b) D.L.Minor, Jr., P. S.Kim, ibid. 1994.367.660-663;c) C.K.Smith. J. M. Withka, L.
Regan, Biochemistry 1994,33. 5510-5517.
0 VCH Verl~gs~essrll~schuf~
mbH, 0-69451 Weinheim,t995
0570-0833~95j0IOl-0097
3 I0.00+ . 2 5 0
97
a
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J. S. Balcei-ski, E. S. Pysh, G. M . Bonora. ('. Toniolo. J Aru. < ' / i c w i . .SO(
1976. 9K. 3470 -3473: b ) D. S. Kenip. B. R. Bowen. E i r d i d r o ~ L?ri.
i
1988. 29,
1 -50x7: c) D. S. Keinp. B. R. Bowcn. C. C Mucndel. .I Or? ('licm 1990.
4650 4657: d ) K . Y. Tsang. H . Diar. N . Graciani. J. W. Kelly.J. Am. U i w u
S I K . 1994. I l h , 398X- 4005
(31
ii)
14)
:I)
K.-C. Chou. G . Ntinethy. H . A. Sclicrnga. B!o~/ic~ri;.~rri~
1983. 22. 0213
6221 : h ) S. Lifwn. C. Sander. jVu/iire ( L f i i i h i ) 1979. 282. 109 I1 I.c ) K -C.
Choii, G. Niinethy. H. A. Schcl.ng:i. .Arc- C/iw?.Kc.3. 1990. 23. 134 141.
[ 5 ] ; I ) G Seipke. H . A. Arlm:inn, K . C i . W;igner. B i o / x i / w i m 1974. /.t. 1621
16-33; b ) A. Brack. L. Orgel. ,Vo/rirc ( L o d o i i ) 1975. 3 6 . 3X.3 387: c ) S S .
Picrrec. R . 7. Ingwnll. M. S. V;ii-lander. M. Goodman. ~ ~ ~ J ~ I J / 1978.
~ ~ ~ ~17.
I ~
1837-1X47: d ) D. G. Osterman. E. T. Kaiser. ./. C d / . B ; o d i m . 1985. 20. 57
72; c ) K.-11. Altinann. A . Fliir\heimer. M. Muttcr. /!it. J t ' q i r . f ' n i r i 4 i Rc5.
1986. 2?. 314~-319.e) M . Muttcr. R. Gassimnn. U Buttkw. K.-H. Altni;inn.
A , I # l ~ l I . ~ ~ / l ( ~ l1991,
l l
1113. 1504 -1506: A l , , q l ~ l l .(%e,ir. h l l . Ed. h1,q/. 1991. 30.
.
4wd.
1514- 1516: 1) S. Zhang. T. Holrneb. C. Lockshin. A. Rich. P r i ~ r Xui/
S1.i O S A 1993. 90. 3334 -.1338.
(61 M. R . Ghadiri. K . Kobayashi. J. R. Gi-anja. R . K Chadhii. D E. McRce.
,4n,yctr. (%rnl. 1995. 107. 76 ~ 7 8Ayccitc
:
C%ct>r. In!,E d Log/. 1995. 34. 9 3 . 95
~
171 a ) M R . Cihadiri. J. R Grnnja. R . A Milligan. D. E. McRee. N . Kh:izanovich.
.Voiiirc ( L I J ~ I ~
1993.
~ I I 366,
I ) 324 317: b ) M. R . Ghadiri. J. R . Granja, L . K .
Buclilcr. i / d 1994. 369. 301 304: c ) N . Khaznno\ich. I . R. Granjii. D. E.
McRee. R . A. Milligan. M . R . Ghiidii-i. .I . 4 C/iwi.
~
.Sii(c 1991. 116. 6011 6012.
1x1 Thecyclic peptide htructure. d t h o u p h representing :I limiting form ofhackbone
tUist. has backbone $ and v, angles (-12X.4 m d 126.7 . respectively. for Phc
;md 131.5 and - 146 2 respectively. h r A h ) that are well within the iillowed
/)-sheet I-cgions of the Ramach;indr;in map.
[9] This specics has been fully chnracterited by the observed exchange ;ind N O €
cross pe:iks in the ROESY cpecti-um. Additional support for the Ihrmation of
this new diineric ensemble
prolided bq deuterium labeling Ftiidies. T h e
aniide backbone protons of peptide I Liere lirst exchanged n ith deuteriuni
(96 2 % incorporation) and thcn mixed w i t h iiii equ;il iiinoiinl of peptide 2.
Analysis of the ' H N M R spectrum. comparing the intensity ol'the N H resonanccs t o those of the 2 and /,protons and o l the side chain, indicnted d
SO i 4 % reduction in the N H signal intensity. thus unequi\ncally e s t a h h h i n g
the dimcric state of the new /$-sheet enbemhle.
[lo] Because d t h e fourfold synimeti-y along the 'ixis perpendicular t o the plane of
t h e ring. the enantiomeric peptidea 1 a n d 2 ciin only lorin one type of antiparallel /]-sheet ensemble (four equivalent hydi-ogen-bonding position\) in M hich
A h Aln and Phc- Phe residues make up the near neighbor ci-oa\-strand pair\.
However. in the c;ise of peptide 3 in which o n l y ii twofold symmetry d o n g the
same axis exists. t w o diastei-eoineric /{-sheet structures arc possiblc. Because
both enscinhles have identical hydrogei~-hoiidingintcriictioiis between the
backbones, the relative population of the two diastereomers will be dictated bq
the difference in the energetic conrrihutiona o f the neiiicst neighbor crossstrand i n t e r x t i o n s h e t w e n side chains.
[ I l l All N M R resonances. including the sets belonging t o 3a ;ind 3 b ensembles.
were assigned with the aid o f ROESY spectroscopy. ' H N M R studies indicate
the formation of a 4 8 : 5 1( k O . 5 ) mixture of the two diastereomers corresponding to AAGZqi= 4X
14 calmol '. We were unahle to assign with high conlidence which set o f signals belonged to the diastereomers 3 a 01- 3b.Thercforc.
for illustrative simplicity we have arbitrarily assigned each set of resonances t o
3 a o r 3 b i n Figure 1
.
*
Synthesis and Structure of a Dendritic
Polysilane**
Joseph B. Lambert," Jodi L. Pflug, and
Charlotte L. Stern
The chemistry of oligo- and polymeric silanes, (- SiRz - ) , z ,
has blossomed over the last 20 years.['] These molecules are of
interest for their structural, electronic, optical, and chemical
properties. These advantageous properties, however, can be off[*] Prof. J. B. Lamhei-t, J. L. Plliiy. C. L. Slern
Department of Chemistry
Northwestern University
Evanston. IL 60708-31 13 ( U S A )
Telefax: Int. code +708-491-7713
[**I
98
This work was supported hy the National Science Foundation ( G r a n t No.
CHE-9302747). We thank Mr. J. M . Denari for measuring the extinction coefficients.
set by the lability of the Si--Si bonds. which have low bond
dissociation energy in polysilane chains compared with C - C
bonds in hydrocarbon
The Si -Si bonds can be isomerized by acid catalysts and can be cleaved by nucleophiles. electrophiles. or light."' On a different front, the last 10 years have
seen the rapid rise in the study of dendritic polymers. whose
repeatedly branched structure emanates from a single core."]
Such materials tend toward the shape of 21 sphere. and ni;iny
bonds are in;iccessible to attack by reagents in solution.
We have sought to prepare dendrimers composed entirely of
polysilane chains, with the expectation that the less accessible
inner Si -Si bonds would exhibit high stability. Because the dendritic structure contains I I multiplicity of branching sites, the
longest polysilane chain is repeated many times. Such structural
redundancy means that a single Si-Si scission most likely will
not alter the optical or electronic properties that make polysilanes important.
Except for a few simple compounds with a core Si bonded to
three or four Si atoms. that is. so-called zeroth generation dendrimers such a s (Me,Si),Si. to our knowledge there are no
known dendritic polysilanes. We report herein the preparation
and crystal structure of the first such example. niethyl[tris(permethylneopentusilyl)]sil~~ne
(
in which the longest poly-
~ I ' ~
[ ( M c Si SiSi M c L] ,S i M e
1
silane chain of seven silicon a t o m is repeated 27 times in the
dendritic structure. The core silicon atom in 1 is bonded to ;I
methyl group and to three dimethylsilyl groups that serve as
spacers to the next branching point, which is a silicon atom to
which three trimethylsilyl groups are attached. Scission of one
of the peripheral Si- Si bonds in a tris(trimethylsily1)silyl group
still would leave 21 intact Si, pathways. Even scission of two
such Si-Si bonds would leave I S or 16 Si, pathways, depending
on whether the two Si-Si bonds are in respectively the same or
different tris(trimethylsily1)silyl groups. Scission of a Si -Si
bond on either side of a spacer dimethylsilanediyl group would
remove one of the three dendrons or wedges but still leave nine
Si, pathways. This molecule therefore illustrates the redundancy present in dendritic polysilanes.
The dendrimer I was prepared starting from commercially
available tris(trimetliylsilyl)silane, which was converted in 90 O/o
yield to methyl[tris(trimethylsilyl)]silane by sequential treatment with chloroform (or carbon tetrachloride) and methyllithiurn. Treatment of the resulting silane with chlorotrimethylsilane
and aluminum trichloride according to the method of lshikawa
et al."] yielded methyl[tris(chlorodimethylsilyl)]silane in 7 5 %
yield after purification by distillation. A single chlorine atom on
one of the SiMe, substituents deactivates the group to further
demethylationl'chlorination ; thus the reaction time and temperature were chosen to ensure that the trichlorinated level was
reached. Subsequent reaction of the trichlorinated silane with
tris(trimethylsilyl)silyllithiumL"l in methyltetrahydrofuran at
- 15 C yielded the dendrimer I in 85 YOyield after recrystallization.
The white solid 1 does not sublime but softens around 1 50 C.
The highest cluster in the mass spectrum has its largest peak at
m/= 945. which corresponds to loss of methyl from the expected
largest peak in the parent isotopic cluster. which would occur at
( M + 2) or 960. The most abundant peak. at q ' z 305, corresponds to the permethylneopentasilyl group (one wedge). The
'"Si N M R spectrum contains peaks at 6 = - 69.6 from the core
silicon, at (5 = - 26.7 for the silicon atoms of the spacer
(Me,Si). at 6 = - 124 for the silicon atoms at the first generation branching point, and at (5 = - 9.44 for the peripheral
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