Structure Determination of Two Stereoisomers of Sevoflurane Dimer
by CP-FTMW Spectroscopy
Nathan A. Seifert, Cristobal Perez, Daniel P. Zaleski, Justin L. Neill, Brooks H. Pate
University of Virginia
Alberto Lesarri, Montserrat Vallejo-López
Universidad de Valladolid
Emilio J. Cocincero, Fernando Castaño
Universidad del País Vasco
Introduction
In 2011…
Suhm and coworkers observed bands blue-shifted
from their monomer peaks and tentatively assigned them
to larger sevoflurane oligomers (dimers, ++)
Sevoflurane homodimers have a
number of potential stabilizing factors:
Diastereomeric pair observed in CP-FTMW
scan:
Donor
-OCH2F a solid
Lewis base
C-H/F hydrogen bonding?
Acceptor
Two strong deactivating groups (-CF3)
Mild donating group (-OCH2F)
 C-H is a good Lewis acid
(SS) [pictured]
(SR) [pictured]
Experimental
Some facts about the
new sevoflurane spectrum…
9.1 million averages
Dynamic range: 31000:1
Average FWHM: 60 kHz
9,600 lines over 4:1 SNR (1.6 MHz-1)
Spectrometer setup
identical to sevoflurane-benzene
(previous talk)
0.2% sevoflurane in Ne, 1 atm backing pressure
Heterochiral Dimer
Theory
Parameter
MP2
B3LYP
M06-2X
A (% Err vs Exp)
306.56 (0.59%)
299.51 (1.7%)
309.30 (1.5%)
B (% Err)
183.87(4.7%)
160.94 (8.3%)
188.37 (7.3%)
C (% Err)
174.85 (4.5%)
155.31 (7.1%)
177.53 (6.1%)
μa, μb, μc
2.0, 1.4, 0.02
1.2, 1.8, 0.22
2.5, 1.4, 0.13
ΔEbinding (cm-1)
-4117.78
-1369.35
-3117.40
ΔEbindingCP (cm-1)
-1252.15
64.90 (!)
-2062.25
Experiment
• Observed all
8 13C isotopologues in
natural abundance
• Avg. 130 transitions per
isotopologue, for a total
of 1720 assigned heterochiral
transitions
Parameter
Fit Value
A (MHz)
304.70026(39)
B (MHz)
175.56391(18)
C (MHz)
167.25458(18)
ΔJ (kHz)
0.00850(24)
ΔJK (kHz)
0.04428(62)
ΔK (kHz)
-0.0487(13)
Nlines
725
σrms (kHz)
7.25
Homochiral Dimer
Theory
Parameter
MP2
B3LYP
M06-2X
A (% Err vs Exp)
308.11 (0.15%)
308.34 (0.18%)
314.05 (2.0%)
B (% Err)
181.76 (3.1%)
174.22 (0.68%)
185.89 (4.5%)
C (% Err)
172.83 (1.4%)
168.44 (0.00%)
182.49 (4.6%)
μ a, μ b, μ c
1.8, 0.5, 3.3
1.7, 1.2, 2.7
1.9, 1.1, 3.1
ΔEbinding (cm-1)
-4216.41
-1412.18
-3376.27
ΔEbindingCP (cm-1)
-1275.05
4.36
-2257.76
ΔΔEbCP (cm-1)
-22.91
-60.54
-195.12
• Observed all
8 13C and both 18O isotopologues
in natural abundance
• A total of 1770 assigned
homochiral transitions
Experiment
Parameter
Fit Value
A (MHz)
307.789308(39)
B (MHz)
172.119904(23)
C (MHz)
168.437022(23)
ΔJ (kHz)
0.011420(29)
ΔJK (kHz)
0.029193(43)
ΔK (kHz)
-0.035955(67)
Nlines
1051
σrms (kHz)
8.19
Intermolecular r0 structure fit
Homochiral
Schema:
• Nearly exact procedure also used
for fitting heterochiral dimer (no oxygen isotopologues,
so purely carbon-containing parameters were fit)
•
Fix monomer geometry to
ab initio (excellent
agreement with monomer
FTMW results)
•
Vary three intermolecular
parameters (…in theory)
• In STRFIT, better results
using dummy atom
coordinate system and
fitting these parameters
effectively
Structural Results
Homochiral
σfit = 0.0253 amu Å2
Significant issues
with imaginary
coordinates
R0
Heterochiral
σfit = 0.0209 amu Å2
Pictured: MP2/6-311++g(d,p) ab initio structure with r0/rs coordinates as small blue spheres
Rs
No issues
with imaginary
coordinates
Structural Comparison
Homochiral
Heterochiral
Evaluating the C-H⋯F interactions1:
• Typical interactions are around 2.6 Å (average)
• <[C-H⋯F] ≈ 135° for a good average C-H⋯F bond
• (sevo)2 <[C-H⋯F] ≈ 125-140°
1. H.-J. Schneider, Chem. Sci., 3 (2012), 1381, and references therein.
Conclusions
•
Structural determination of two diastereomers of (sevoflurane)2
• 24 heavy atoms per cluster!
• Issues with imaginary coordinates easily overcome by use of a simple
intermolecular r0 fit
What else can we learn from this spectrum?
• The (RR) and (RS) dimers, though spectrally dense, only represent ~40% of the lines > 4:1 SNR
• (sevo)1 (w/ isotopes) + (sevo)2 represents somewhere around ~60% of the transitions
Therefore, an open question: what else is being formed in the jet?
• (sevo)(H2O) is a possibility, but (H2O)2 is weak in this acquisition [a typical indicator of “wetness”]
• Higher order (sevo)n clusters? Other isomers?
• Discovery bottlenecked mostly by the speed/efficiency of computational methods
Acknowledgements
Pate Group
Brooks Pate
Cristobal Perez
Simon Lobsiger
Luca Evangelisti
Thanks for your time!
Brent Harris
Amanda Steber
Nathan Seifert
Newcastle University
Daniel Zaleski
Brightspec
Justin Neill
Universidad de Valladolid
Alberto Lesarri
Montserrat Vallejo-López
UPV-EHV
Emilio J. Cocincero
Fernando Castaño
Thanks to the NSF for funding:
MRI-R2, Award CHE-0960074
Heterochiral Dimer Structure Results
Fit Parameter
R0 value
Rs value
MP2/6-311+g(d,p)
R(C⋯C) / Å
4.286(9)
4.23(4)
4.124
Θ(Cdonor⋯Cacc-CH2F) / °
71.5(2)
72.2(12)
73.2
Φ(Ca-C⋯C-Ca) / °
61.6(4)
(pictured)
62(1)
65.6
Lack of imaginary coordinates saves the day for the
Kraitchman determination!
Alternation of short/long C-F ⋯ H bonds with respect
to homochiral isomer
Homochiral Dimer Structure Results
Fit Parameter
R0 value
Rs value
MP2/6311++g(d,p)
R(C⋯C) / Å
4.328(5)
4.33(5)
4.115
Θ(C⋯C-O) / °
41.5(1)
48(2)
41.4
Φ(O-C⋯C-O) / °
66.8(7)
(pictured)
45(4)
66.3
C-F ⋯ H interactions quite important, unlike
in sevoflurane⋯benzene
Evaluating the C-H⋯F interactions1:
• Typical interactions are around 2.6 Å (average)
• <[C-H⋯F] ≈ 135° for a good average C-H⋯F bond
• (sevo)2 <[C-H⋯F] ≈ 125-140°
1. H.-J. Schneider, Chem. Sci., 3 (2012), 1381, and references therein.