An Improved Analysis of the Sevoflurane ⋯ Benzene Structure 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 Isabelle Kleiner Laboratore Interuniversitaire des Systèmes Atmosphériques (LISA)

A recap from last year Experimental r s coordinates for benzene hydrogens using sevoflurane ⋯ benzene-d 1 Sevoflurane monomer coordinates derived from monomer FTMW study 1 Sensitivity insufficient for any 13 C isotopologues in natural abundance! BELGI-C 1 fit of internal rotation with 135 a-type transitions, determined V 6 = 32.88(3) cm -1 Open problems from last year: Sensitivity of instrument too low to achieve full experimental structure μ a = 2.3 D, μ c = 1.7 (DFT values); no c-types detected in original spectrum, however. The existence of other conformers unclear (Suhm and coworkers report two in IR study 2 ) Spectrum complicated by high barrier, six-fold internal rotation 1. Lesarri, A., et al. Phys. Chem. Chem. Phys. 2010, 12, Dom, J. J., et al. Phys. Chem. Chem. Phys. 2011, 13, , MH13: What we could achieve in previous study:

Experimental New improvements to 2-8 GHz (see Cristobal’s talk, TH10, for more information) New horns with improved directionality enable 5 pulsed nozzles (1-2 nozzles previously) New TWT (Appl. Sys. Engin. 167X/KU) with 600W peak output (200W peak power previously) New oscilloscope (Tek DPO73304D) enables detection of 8 4μs pulse frames at an effective rate of 3.3 Hz with 40μs detection gate (previous 2-8GHz rate was ~0.5Hz!) High phase stability at 2-8 GHz allows for long term averaging, even with stops to repressurize the chamber for routine maintenance Data sets obtained: 1) 0.2% sevoflurane / 0.2% benz in Ne, 10.8 million averages 2) 0.2% sevo / 0.2% benz-d 1 in Ne, 6.5 million averages

Some facts about… Sevoflurane + benzene-d million averages Dynamic range: 20000:1 Average FWHM: 60 kHz 10,360 lines over 4:1 SNR (1.7 MHz -1 !) Spectroscopic Results sevoflurane monomer sevoflurane-benzene-d 1 (6x) 13 C 1 -sevoflurane-benzene-d 1 (33x) We now have enough sensitivity for 13 C isotopologues in natural abundance! The real success of this spectrum:

BELGI Fit: The old… J = J = 5 - 4, K a ≥ 2 J = , K a ≥ 1 (Ab-initio dipoles used for intensities)

BELGI Fit:..and the new J = J = 5 - 4, K a ≥ 2 J = , K a ≥ 1 (Ab-initio dipoles used for intensities)

One more comparison for good measure… (scaled for noise) Old 2-8 GHz spectrum New 2-8 GHz spectrum (Scaled for noise)

Parameter Lit. Label OperatorValue OA (MHz)APa2Pa (15) PAM value"Ja2Ja (15) B (MHz)BPb2Pb (12) PAM value"Jb2Jb (12) C (MHz)CPc2Pc (84) PAM value"Jc2Jc (84) V 6 (cm -1 )V6V6 (1-cos(6α))/ (27) RHORHO (unitless) ΡPαPaPαPa (54) F (MHz)FPa2Pa2 [ ] DELTA (MHz)F ab P α 2 {P a,P b } (44) DAB (MHz)D ab {P a,P b }25.40(24) DACI (MHz)D aci {P a,P c }17.945(81) DJ (kHz)ΔJΔJ -P (23) DJK (kHz)Δ JK -P 2 P a (85) DK (kHz)ΔKΔK -P a (81) C11 (MHz)V 6bc (1-cos(6α))(P b 2 -P c 2 )-13.45(40) BK2 (MHz)V 6K (1-cos(6α))(P a 2 )-13.2(48) AK2 (MHz)FKFK Pα2Pa2Pα2Pa (28) Fit Statistics N (A/B states)178 σ AB (kHz)6.3 N (E states)123 σ E (kHz)9.7 N (total)301 σ (kHz)7.7 Direction CosinesExperimentM06-2X cos(λ a ) cos(λ b ) cos(λ c ) Improved BELGI-C 1 Fit Results High-barrier six-fold internal rotation Consistent with C 6 symmetry: Spin weights of 10:44:22:18 consistent with observed relative intensities Fit includes new c-types and a-types with K a ≤ 6 (A,E 1 ) doublets fit as v t = 0 -> 0 transitions (B,E 2 ) doublets fit as v t = 1 -> 1 transitions C 3 basis J=0, K=0

Conformational Search Conformers reported by Suhm & coworkers 1 1. Dom, J. J., et al. Phys. Chem. Chem. Phys. 2011, 13, All structures & values derived using MP2/ g(d,p) + counterpoise corrections MM force field conformer scan detected 95 conformers within 43 kJ mol -1 (M06-2X/ g(d,p) energies, ZPE corrected) (~15:1 in Xe cryosol’n)

Isotopologue Assignments 6 2 D positions X C positions = 60 total possible 13 C/ 2 D isotopologues However, 1- 2 D and 2- 2 D signals much weaker than other 4, so only 40 max are detectable Final assignments (too many to list in detail here!): Refined six 2 D benzene isotopologue fits (avg. ~250 lines/isotopologue) 33 2 D/ 13 C isotopologues (other 7 are buried) All six 13 C benzene isotopologues What can we do with all of this data? Full r 0 structure fit, including fluorines! (Thanks to Z. Kisiel for updating STRFIT to allow this many isotopic species in the input file!) (Sevoflurane 13 C isotopologues are complicated by internal rotation, so they’ve been left alone. But they’re there and quite strong!) A single overnight Autofit run detected C/ 2 D isotopologues

MP2/ g(d,p) + BSSE corrections r 0 experimental structure Take home points: CF ⋯ H interactions are weakly contributing CF ⋯ H bonds in CSD database, on average, ~2.6 Å 1 1) Schneider, H-J. Phys Chem Chem Phys. 2012, 3, ) Fuiji, A., et al. J. Phys. Chem. A. 2004, 108, ) Dey, R. C.; Seal, P.; Chakrabarti, S. J. Phys. Chem. A. 2009, 113, CH ⋯ π interaction very dominant! HCCH ⋯ Ph : 3.5 Å (CCSD) 2 CHX 3 ⋯ Ph: 3.69 Å (X = H) ≤ r ≤ 3.39 Å (X = F) 3 Structural Results Parameters fixed: Sevoflurane hydrogen positions <(F-C-F) in perfluoro groups (r[C-F] was floated) r 0 σ fit = amu Å 2

Conclusions Take home points CP-FTMW sensitivity enables full r 0 structural determination in one experiment Can’t do much better, outside radioisotopic substitution of F (obviously not realistic in the slightest) BELGI fit improved: includes new a-types and c-types with K a ≤ 6, fit RMS = 7.7 kHz Some issues with fitting the E 1 /E 2 states in particular What else could be hiding in the spectrum? Higher order clusters Sevo-(benz) 2 ? What wins -- T-shaped benzene dimer + sevoflurane, or benzene at two different binding sites? or ? M06-2X/ g(d,p) optimized geometries

Acknowledgements Thanks to the NSF for funding: MRI-R2, Award CHE Pate Group Brooks Pate Cristobal Perez Simon Lobsiger Luca Evangelisti Brent Harris Amanda Steber Nathan Seifert Daniel Zaleski Newcastle University Brightspec Justin Neill Universidad de Valladolid Alberto Lesarri Montserrat Vallejo-López Thanks for your time! UPV-EHV Emilio J. Cocincero Fernando Castaño LISA Isabelle Kleiner Thanks to Zbiginew Kisiel for his improvements to STRFIT!

Isotopologue Assignments - Autofit A (MHz)B (MHz)C (MHz)OMC (kHz)Assignment D D No fit D/ 13 C(1) D/2- 13 C D/3- 13 C D No fit D/ 13 C(4) D D/ 13 C(2) D/4- 13 C D D/5- 13 C No fit D/ 13 C(1) D D/ 13 C(1) Top 18 Autofit Results …but first 1000 fits all have OMC <24 kHz! (See my talk on Thursday morning (RC12), for more info on Autofit) A total of C/ 2 D isotopologues were assigned from a single autofit run (there are very likely more) 9.89 million triples; frequency window ±20 MHz Fit using , , Fit checked with 10 transitions, 7 ≤ J ≤ 10, 0 ≤ K a ≤ 4 (thus, each fit to the left is a 13-line fit)

Structural Results Slight rotation of r 0 /r s coordinates noticable w.r.t. calculated geometry: Low-lying torsional mode contribution?