Encapsulation of protonated diamines in a water-soluble, chiral, supramolecular assembly allows for measurement of hydrogen-bond breaking followed by nitrogen inversion/rotation

Article abstract of DOI:10.1021/ja076691h

Amine nitrogen inversion, difficult to observe in aqueous solution, is followed in a chiral, supramolecular host molecule with purely rotational T-symmetry that reduces the local symmetry of encapsulated monoprotonated diamines and enables the observation and quantification of ΔG ^? for the combined hydrogen-bond breaking and nitrogen inversion/rotation (NIR) process. Free energies of activation for the combined hydrogen-bond breaking and NIR process inside of the chiral assembly were determined by the NMR coalescence method. Activation parameters for ejection of the protonated amines from the assembly confirm that the NIR process responsible for the coalescence behavior occurs inside of the assembly rather than by a guest ejection/NIR/re-encapsulation mechanism. For one of the diamines, N,N,N′,N′-tetramethylethylenediamine, the relative energy barriers for the hydrogen-bond breaking and NIR process were calculated at the G3(MP2)//B3LYP/6-31++G(d,p) level of theory, and these agreed well with the experimental data.

Full text of DOI:10.1021/ja076691h

Published on Web 04/29/2008
Encapsulation of Protonated Diamines in a Water-Soluble, Chiral,
Supramolecular Assembly Allows for Measurement of
Hydrogen-Bond Breaking Followed by Nitrogen Inversion/Rotation1
Michael D. Pluth, Robert G. Bergman,* and Kenneth N. Raymond*
Department of Chemistry, UniVersity of California, Berkeley, California 94720, and Chemistry
DiVision, Lawrence Berkeley National Laboratory, Berkeley, California 94720
Received September 17, 2007; E-mail: rbergman@berkeley.edu; raymond@socrates.berkeley.edu
Abstract: Amine nitrogen inversion, difficult to observe in aqueous solution, is followed in a chiral,
supramolecular host molecule with purely rotational T-symmetry that reduces the local symmetry of
encapsulated monoprotonated diamines and enables the observation and quantification of ∆Gq for the
combined hydrogen-bond breaking and nitrogen inversion/rotation (NIR) process. Free energies of activation
for the combined hydrogen-bond breaking and NIR process inside of the chiral assembly were determined
by the NMR coalescence method. Activation parameters for ejection of the protonated amines from the
assembly confirm that the NIR process responsible for the coalescence behavior occurs inside of the
assembly rather than by a guest ejection/NIR/re-encapsulation mechanism. For one of the diamines,
N,N,N′,N′-tetramethylethylenediamine, the relative energy barriers for the hydrogen-bond breaking and
NIR process were calculated at the G3(MP2)//B3LYP/6-31++G(d,p) level of theory, and these agreed
well with the experimental data.
Introduction
hydrogens R to the nitrogen of prochiral amines or monitoring
the NMR spectra of prochiral amines as a function of pH.9–13
Nitrogen pyramidal inversion (umbrella inversion motion) in
amines involves moving the lone pair from one side of the
tetrahedral amine structure to the other. Studies of amine
nitrogen inversion have come from most disciplines of chem-
istry, including theoretical, computational, synthetic, and bio-
logical chemistry.2–6 However, direct measurement of the rapid
rate of this transformation in solution is difficult. Most measure-
ments of the inversion free-energy barrier7 have come from gas-
phase far-infrared or microwave spectroscopies.8 Inversion
barriers in the gas phase for alkylamines generally do not exceed
9 kcal/mol, but steric hindrance, hybridization changes, or
hydrogen bonding can increase the barrier by g5 kcal/mol.9
Most measurements of nitrogen inversion barriers in solution
have come from NMR solution studies and rely on monitoring
changes in the chemical environment of functional groups near
the nitrogen atom. This can be aided by monitoring enantiotopic
Although often referred to as nitrogen inversion in the literature,
solution measurements of the inversion process almost always
measure a combined nitrogen inversion/rotation (NIR), which
is required to change the chemical environment of the functional
groups being monitored.14,15
Because of the experimental difficulties of probing NIR
processes with low activation barriers by NMR, most NMR
studies have necessarily focused on amines with higher inversion
barriers enforced by specific structural or electronic constraints,
such as those in aziridines (10-20 kcal/mol),16,17 diaziridines
(20-30 kcal/mol),18,19 azanorbornanes (>13 kcal/mol),20,21
hydrogen-bonded amines (10-20 kcal/mol),9,22 or sterically
hindered amines.14 Recent work has also focused on controlling
the rate of nitrogen inversion by a variety of strategies, such as
(10) Saunders, M.; Yamada, F. J. Am. Chem. Soc. 1963, 85, 1882.
(11) Bardos, T. J.; Szantay, C.; Navada, C. K. J. Am. Chem. Soc. 1965,
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(1) Paper number 40 in the series Coordination Number Incommensurate
Cluster Formation. For the previous paper in the series see: Pluth,
M. D.; Tiedemann, B. E. F.; van Halbeek, H.; Nunlist, R.; Raymond,
K. N. Inorg. Chem. 2008, 47, 1411.
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7034.
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1991, 56, 1731.
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(7) All of the energy barriers measured in this paper are free energies of
activation.
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Soc. 1989, 111, 1776.
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S. N.; Rospenk, M.; Koll, A.; Sobczyk, L. Magn. Reson. Chem. 1993,
31, 1034.
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1996, 118, 7783.
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3016.
9
6362 J. AM. CHEM. SOC. 2008, 130, 6362–6366
10.1021/ja076691h CCC: $40.75
2008 American Chemical Society

Encapsulated Diamines and Measurement of H-Bond Breaking/NIR
A R T I C L E S
Figure 2. Scope of monoamines and diamines investigated.
increase the basicity of the encapsulated guest,31 a property that
was used to facilitate the acid-catalyzed hydrolysis of encap-
sulated orthoformates32 and acetals33 in basic solution. Follow-
ing the amine protonation studies, we hoped to use the chirality
of 1 to observe the NIR process of encapsulated diamine guests.
Although chelating diamines such as N,N,N′,N′-tetramethyl-
ethylenediamine (2) have idealized C2V symmetry, encapsulation
in the chiral T-symmetric host reduces the symmetry of the guest
to C2. This renders the geminal nitrogen methyl groups
inequivalent, which enables detection of hydrogen-bond break-
Figure 1. (Left) Schematic representation of 1 with only one ligand shown
for clarity. (Right) Space-filling model of 1.
Scheme 1
1
ing followed by NIR by H NMR. One possible mechanism
for the NIR for chelating amines is outlined in Scheme 1. In
the initial structures, the A (blue) and B (red) methyl groups
are inequivalent because of the symmetry imposed by 1.
Breaking one N-H hydrogen bond (a) allows one nitrogen
stereocenter to invert (b), followed by bond rotation (c) and
finally by re-formation of the hydrogen bond (d).34 In this
process, the A and B methyl groups exchange. If this process
occurs rapidly on the NMR time scale, only one resonance
corresponding to the methyl groups will be observed. Con-
versely, if the exchange process is slow on the NMR time scale,
two methyl resonances should be observed. Furthermore, the
constrained environment of the interior cavity of 1 should
increase the inversion barrier of encapsulated protonated amines,
thereby facilitating detection.
redox switching23 or metal coordination.24 Herein, we report
the use of the constrained guest environment of a self-assembled
supramolecular assembly to detect the hydrogen-bond breaking
followed by NIR of encapsulated monoprotonated diamines and
to quantify the associated energy barrier for the combined
process.
Results and Discussion
We have previously described the formation and chemistry
of the tetrahedral supramolecular assembly [Ga4L6]12- (1, L )
N,N′-bis(2,3-dihydroxybenzoyl)-1,5-diaminonaphthalene, Figure
1).25–28 The -12 overall charge of 1 imparts water solubility,
whereas the naphthalene walls provide a hydrophobic cavity
which is isolated from the bulk aqueous solution. The tris-
bidentate coordination at the metal vertices makes each vertex
a stereocenter, and the strong mechanical coupling of the ligands
transfers the chirality of one metal vertex to the others (forming
the mirror image ∆∆∆∆ or ΛΛΛΛ homochiral enantiomers
of the assembly).29 With purely rotational T point group
symmetry, 1 has been exploited for the diastereoselective
encapsulation and reactivity of organometallic complexes and
the dynamic resolution of ruthenium sandwich and half-
sandwich complexes.30 We have recently reported the ability
of 1 to encapsulate monoprotonated amines and dramatically
In screening potential guests, a number of monoamines and
diamines containing geminal N-alkyl groups were investigated
(Figure 2). Our recent work with protonated amine and
phosphine guests has shown that the guests are encapsulated in
their monoprotonated form.31 The host-guest complexes of the
encapsulated protonated amines in 1 are stable in both aqueous
and nonaqueous solutions. Neutral guests can also be encap-
sulated in 1, but because the encapsulation is driven by the
hydrophobic effect, addition of nonaqueous solvents prohibits
encapsulation.35
1
At room temperature in D2O, the H NMR of host-guest
complexes of amines such as 2 and 3 showed only one signal
corresponding to the geminal N-methyl groups on the nitrogen
atoms, suggesting fast NIR on the NMR time scale. However,
in the case of 4, two distinct geminal methyl signals were
observed, suggesting that the hydrogen-bond breaking/NIR
process was slow on the NMR time scale. The freezing point
of water limited accessible temperatures low enough to observe
decoalesence of the averaged resonances for amines 2 and 3.
Therefore, methanol was used as a solvent to obtain a greater
(23) Davies, M. W.; Shipman, M.; Tucker, J. H. R.; Walsh, T. R. J. Am.
Chem. Soc. 2006, 128, 14260.
(24) Davies, M. W.; Clarke, A. J.; Clarkson, G. J.; Shipman, M.; Tucker,
J. H. R. Chem. Commun. 2007, 5078.
(25) Caulder, D. L.; Powers, R. E.; Parac, T. N.; Raymond, K. N. Angew.
Chem., Int. Ed. 1998, 37, 1840.
(26) Caulder, D. L.; Raymond, K. N. J. Chem. Soc, Dalton Trans. Inorg.
Chem. 1999, 8, 1185.
(31) Pluth, M. D.; Bergman, R. G.; Raymond, K. N. J. Am. Chem. Soc.
2007, 129, 11459.
(27) Davis, A. V.; Fiedler, D.; Seeber, G.; Zahl, A.; van Eldik, R.; Raymond,
K. N. J. Am. Chem. Soc. 2006, 128, 1324.
(32) Pluth, M. D.; Bergman, R. G.; Raymond, K. N. Science 2007, 316,
85.
(28) Davis, A. V.; Raymond, K. N. J. Am. Chem. Soc. 2005, 127, 7912.
(29) Davis, A. V.; Fiedler, D.; Ziegler, M.; Terpin, A.; Raymond, K. N.
J. Am. Chem. Soc. 2007, 129, 15354.
(33) Pluth, M. D.; Bergman, R. G.; Raymond, K. N. Angew. Chem., Int.
Ed. 2007, 46, 8587.
(34) Bond rotation could also precede nitrogen inversion.
(35) Biros, S. M.; Bergman, R. G.; Raymond, K. N. J. Am. Chem. Soc.
2007, 129, 12094.
(30) Fiedler, D.; Leung, D. H.; Bergman, R. G.; Raymond, K. N. Acc.
Chem. Res. 2005, 38, 349.
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A R T I C L E S
Pluth et al.
Figure 3. Variable temperature 1H NMR spectra of encapsulated N,N,N′,N′-
tetramethyl-1,5-diaminopentane (5). Methyl resonances are highlighted with
blue b (500 MHz, CD3OD, 15 mM 1).
Figure 4. Energy diagram for amine exchange and inversion in 1. Solid
temperature range for variable-temperature experiments. This
solvent choice was also advantageous because it prevented
encapsulation of the neutral form of the guests. Lowering the
temperature of an amine-encapsulated complex in methanol did
slow the hydrogen-bond breaking/NIR process sufficiently, such
that decoalescence in the 1H NMR spectrum was observed. As
the temperature was lowered, the peak corresponding to the
N-alkyl protons broadened and then separated into two different
resonances (Figure 3).
line, ∆Gq
< ∆Gqexch; dotted line, ∆Gq
< ∆GqNIR. R and S refer to
NIR
exch
the two forms of the amine where the geminal N-methyl groups have
changed places. ∆Gq
NIR process.
refers to the combined hydrogen-bond breaking/
NIR
Table 1. Comparison of Activation Free Energies for Guest
Exchange (∆Gqexch) and Energy Barriers for Coalescence Behavior
(∆Gcoal) in 1
a
exch
guest
Tc (K)
∆Gq (kcal mol-1
)
∆Gq
(kcal mol-1
)
∆∆Gqb (kcal mol-1
)
coal
By monitoring each host-guest complex as a function of
temperature, coalescence behavior was observed for the geminal
N-alkyl groups on amines 2-11. Measurement of the difference
in Hertz (∆υ) between the decoalesced peaks at the slow
exchange limit allows for the determination of the rate of
exchange at the point of coalescence (eq 1). By determining
the coalescence temperature (Tc) for the hydrogen-bond break-
ing/NIR process, the free energy of activation for the coales-
cence process can be determined by standard methods (eq 2).36,37
2
3
4
5
6
7
8
9
244 ( 2
231 ( 2
344 ( 2
293 ( 2
288 ( 2
339 ( 2
328 ( 2
326 ( 2
11.0 ( 0.2
10.3 ( 0.2
15.7 ( 0.2
13.5 ( 0.2
13.1 ( 0.2
16.2 ( 0.2
14.2 ( 0.2
14.9 ( 0.2
16.8 ( 0.2
13.8 ( 0.2
17.2 ( 0.2
16.9 ( 0.8
19.1 ( 0.5
15.1 ( 0.2
15.0 ( 0.6
19.7 ( 0.8
14.8 ( 0.9
14.2 ( 0.3
17.5 ( 0.9
13.3 ( 0.7
6.2 ( 0.3
6.6 ( 0.8
3.4 ( 0.5
1.6 ( 0.3
1.9 ( 0.7
3.5 ( 0.9
0.6 ( 0.8
-0.7 ( 0.3
0.7 ( 0.9
-0.5 ( 0.7
10 347 ( 2
11 293 ( 2
a Calculated at Tc. b ∆∆Gq ) ∆Gq
- ∆Gq
.
coal
exch
π
kc ) |∆υ|
(1)
(2)
√
2
hydrogen-bond breaking and NIR process. Because the geminal
methyl groups are both enantiotopic and isosteric, the ground-
state energy of the encapsulated amine is not changed after
inversion.
RTc
∆Gq ) RTc ln
(
)
kcNAh
On the basis of the mechanism for hydrogen-bond breaking
followed by NIR described in Scheme 1, it was somewhat
unexpected that monoamines showed coalescence behavior,
because the proposed mechanism requires a second nitrogen
atom to bind the proton as the other nitrogen inverts. An
alternative mechanism for the observed NMR coalescence could
involve guest exchange, in which an encapsulated amine is
ejected from 1, inverts (or undergoes NIR) in free solution, and
is then re-encapsulated. This would require that the inversion
barrier in solution be lower than in 1, which is consistent with
the highly sterically crowded interior of 1. A qualitative energy
diagram for amine encapsulation followed by hydrogen-bond
breaking and NIR is shown in Figure 4. If the activation barrier
for guest exchange (∆Gqexch) is larger than the activation barrier
for hydrogen-bond breaking and NIR (∆GqNIR), NIR will occur
faster than guest exchange and be observed in the assembly.
In order to confirm that the NIR process responsible for the
coalescence behavior was occurring inside 1 rather than freely
in solution, the energy barriers for guest exchange were
determined by using Eyring analysis of guest exchange rates
measured by using the selective inversion-recovery (SIR) NMR
method at different temperatures.38 (See Supporting Information
for a complete listing of activation enthalpies (∆Hq) and
entropies (∆Sq) for the guest exchange process.) On the basis
of the activation parameters for guest exchange, ∆Gq
was
exch
calculated at the determined coalescence temperature. Com-
parisons of the free energy of activation barrier for guest
exchange (∆Gqexch) and the activation barrier for the coalescence
process (∆Gqcoal) are shown in Table 1. For chelating amines
(2-7), the barrier corresponding to the coalescence process is
lower than the exchange barrier suggesting that the coalescence
behavior is due to the hydrogen-bond breaking/NIR process
occurring in 1. This provides strong support for the conclusion
that NIR is occurring inside the cavity of 1 (i.e., ∆∆Gq > 0,
Figure 3.) and shows that the hydrogen-bond breaking/NIR
process happens much more quickly than guest exchange. For
the small chelating diamines 2 and 3, the difference between
However, if ∆Gq
is equal to or greater than ∆Gqexch, the
NIR
observed ∆GqNIR should be equal to ∆Gqexch, meaning that the
coalescence behavior is due to guest exchange rather than to
(36) Allerhand, A.; Gutowsky, H. S.; Jonas, J.; Meinzer, R. A. J. Am. Chem.
Soc. 1966, 88, 3185.
(37) Line-shape analysis was not possible because of peak broadening upon
encapsulation.
(38) Bain, A. D.; Cramer, J. A. J. Magn. Reson. A 1996, 118, 21.
9
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Encapsulated Diamines and Measurement of H-Bond Breaking/NIR
A R T I C L E S
Scheme 2
2.4 kcal/mol) leads back to 12, which then undergoes C-N bond
rotation in the same manner as in pathway b (TS3, ∆Hq ) 16.3
kcal/mol).
All of the steps in paths b and c are completely reversible
and proceed through the same rate-limiting step (TS3); therefore,
they are likely all contributing to the observed coalescence
behavior. For the encapsulated species, pathway b may be more
prevalent because it leads through a more compact transition
state than structures generated from C-C bond rotation in
pathway c. The longest linear dimension for the structures in
pathway c, where the proton is not chelated, is greater than that
of the more compact structures in pathway b, suggesting that
upon encapsulation in 1, steric interactions with the naphthalene
walls of 1 may play an important role in selecting which of the
two pathways is the most active.
Conclusion
The study of nitrogen inversion is a classic problem in
chemistry and is usually not observable in solution. However,
exploiting the confined and chiral cavity of a synthetic host
molecule enables this observation for protonated diamine guests
in water. The strategy of using local symmetry reduction can
potentially be used as a powerful tool to study a wide variety
of important chemical phenomena that would otherwise be
difficult or impossible to observe.
the inversion barrier and guest exchange is greater than 6 kcal/
mol, which corresponds to the NIR process occurring ∼10 000
times as often as guest exchange.
In contrast to the protonated diamines, protonated monoam-
ines 8-11 showed identical activation barriers for guest
exchange and coalescence. For diamines, one nitrogen can bind
the proton while the other nitrogen inverts. Monoamines,
however, cannot release the proton when encapsulated in 1. The
only way the deprotonation/NIR process can occur with
monamines is for the encapsulated protonated amine to be
ejected from 1; it can then undergo deprotonation followed by
NIR and then re-encapsulation (Scheme 2). If this is occurring,
the free energies of activation for guest exchange and the
coalescence process should be equal, which is observed, as
expected.
Experimental Section
General Procedures. All NMR spectra were obtained by using
a Bruker AV-500 MHz spectrometer. The temperature of all
variable-temperature NMR experiments was calibrated with metha-
nol or ethylene glycol standards.39 SIR experiments were performed
at constant temperature by using a 10 s delay between experiments.
Data points for each SIR experiment were measured by using one
scan with a prescan delay of 10 s. Mixing times were varied from
0.0005 to 18 s in 42 increments. In all cases, the efficiency of the
inversion pulse was greater than 70%.
Computational Methods. All calculations were performed by
using the Gaussian 03 software package with the GaussView
graphical user interface.42 Geometry optimizations, transition state
searches, and unscaled frequency calculations were carried out at
the B3LYP/6-31++G(d,p) level of theory. Frequency calculations
were performed on all converged structures to confirm that they
corresponded to local minima or transition states on their respective
potential-energy surfaces. Transition states were characterized by
the presence of exactly one imaginary frequency. These structures
and frequencies were then used as input in the G3(MP2) zero-point
corrected enthalpy calculations.43,44 Initial structures for transition
states related to bond rotations were obtained by driving the dihedral
angle around the relevant bond in 5° increments at the semi-
empirical (AM1) level of theory.45
In a further study of the NIR mechanism, we sought to probe
the energetics of the individual steps necessary for NIR to occur.
Calculations were performed in Gaussian 03 at the G3(MP2)//
B3LYP/6-31++G(d,p) level of theory (Figure 5) by using 2 as
the model substrate. The first energetic barrier investigated was
the proton transfer between the two nitrogens, which proceeds
through the symmetric structure in TS1. As expected, the barrier
for proton transfer is low ∆Hq ) 2.4 kcal/mol (Figure 5a).
The hydrogen-bond breaking followed by NIR process detected
1
by variable-temperature H NMR studies could occur by one of
two pathways, one requiring nitrogen inversion and rotation around
the C-N bond and the other requiring nitrogen inversion and
rotation around both the C-C and C-N bonds (Figure 5). It
may appear as if the transformations described in Figure 5
violate the principle of microscopic reversibility; however, it
should be noted that the conversions start and end at the same
point on the potential energy surface. This makes the reaction
coordinates cyclic in nature and generates the required symmetry
of the reaction coordinate. In the first pathway, the nitrogen
inverts directly from the ground-state structure 2 through TS2
(∆Hq ) 11.3 kcal/mol) to lead to intermediate 12. Rate-limiting
rotation around the C-N bond (TS3, ∆Hq ) 16.3 kcal/mol)
then occurs to lead back to 1, in which the two geminal methyl
groups on the inverting nitrogen have changed places.
The second pathway, which includes both C-C and C-N
bond rotation, begins with breaking of the hydrogen bond
between the nitrogen and protonated amine followed by rotation
around the C-C bond (TS4, ∆Hq ) 10.3 kcal/mol), leading to
13, where the proton is no longer chelated. Inversion of the
nitrogen (TS5, ∆Hq ) 15.8 kcal/mol) leads to the inverted
intermediate 14. Subsequent C-C bond rotation (TS6, ∆Hq )
Materials. Amines 2-4, 10, and 11 were obtained from Aldrich
and used as received. Deuterated methanol was purchased from
Cambridge Isotope Laboratories and degassed by three freeze-
pump-thaw cycles. Amines 5,46 8,47 and 948 were prepared by
(39) Amman, C.; Meier, P.; Merbach, A. E. J. Magn. Reson. A 1982, 46,
319.
(40) Perrin, C. L.; Dwyer, T. J. Chem. ReV. 1990, 90, 935.
(41) Bain, A.; Cramer, J. A. J. Magn. Reson. A 1993, 103, 217.
(42) Frisch, M. J. et al. Gaussian 03, Revision D.01; Gaussian, Inc.:
Wallingford, CT, 2004.
(43) Curtiss, L. A.; Redfern, P. C.; Raghavachari, K.; Rassolov, V.; Pople,
J. A. J. Chem. Phys. 1999, 110, 4703.
(44) Baboul, A. G.; Curtiss, L. A.; Redfern, P. C.; Raghavachari, K.
J. Chem. Phys. 1999, 110, 7650.
(45) Dewar, M.; Thiel, W. J. Am. Chem. Soc. 1977, 99, 2338.
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Soc. 1979, 101, 5736.
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A R T I C L E S
Pluth et al.
Figure 5. Calculated (G3(MP2)//B3LYP/6-31++G(d,p)) energy coordinate diagram for (a) proton transfer, (b) NIR without C-C bond rotation, and (c)
NIR with C-C bond rotation.
reductive methylation as described in the literature. The host
assembly K12[Ga4L6] was prepared as described in the literature
and precipitated with acetone.25
sistance with calculations, and Dr. Herman van Halbeek and Rudi
Nunlist for NMR assistance. This work was supported by the
Director, Office of Science, Office of Advanced Scientific Comput-
ing Research, Office of Basic Energy Sciences (U.S. Department
of Energy) under contract DE-AC02-05CH11231 and an NSF
predoctoral fellowship to M.D.P.
General Procedure for Amine Encapsulation. In an N2-filled
glovebox, 15.0 mg of K12Ga4L6 was added to an NMR tube, and then,
0.5 mL of CD3OD was added. The amine (5.0 equiv) was added by
syringe, and the NMR tube was shaken for 30 s. For amines with
high coalescence temperatures, the NMR tubes were flame-sealed
under vacuum. Caution: Heating sealed NMR tubes in an NMR probe
to temperatures above the boiling point of the solvent should be done
Supporting Information Available: Experimental details,
NMR characterization, Eyring plots, and further computational
details including optimized geometries, calculated total energies,
and calculated frequencies. This material is available free of
charge via the Internet at http://pubs.acs.org.
1
with great care. H NMR data for the encapsulated monoprotonated
amines both above and below the coalescence temperature are included
in the Supporting Information.
Acknowledgment. We thank Dr. Dennis Leung for helpful
discussions, Dr. Jamin Krinsky and Dr. Kathleen Durkin at the UCB
Molecular Graphics Facility (NSF grant CHE-0233882) for as-
JA076691H
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