Juliane Heitkämper, John C Mullaney, Nick Walker Broadband FTMW Spectroscopy of 2-methylimidazole and Complexes with Water and Argon Chris Medcraft Juliane Heitkämper, John C Mullaney, Nick Walker Newcastle University

Imidazoles Forms the basis of many biomolecules Histidine, Guanine, Adenine, Haemoglobin Imidazole-Based Medicinal Chemistry Many intermolecular interactions possible donate or accept H-bond π-bonding ion–dipole cation–π π–π stacking

Imidazole ChemPhysChem, 2016, 17, 1154 – 1158

Newcastle CP-FTMW Spectrometer Two frequency ranges 2-8 GHz 6.5-18 GHz Hot swappable Laser Ablation Source Nanosecond Nd:YAG 20 mJ/pulse 532nm Brown et. Al., Rev. Sci. Instrum. 79, 053103 (2008)

Laser Ablation Sources

Imidazole ablation products

2-methylimidazole Methyl group may interfere with H-bonding π bonding? Different dimer structure?

Assignment Procedure Internal rotor + 2 nitrogen quadrupoles A-state lines fit using PGOPHER Quadrupole coupling constants Isotopologues  Structure E-state lines identified from similar intensity and quadrupole structure Line centres exported to XIAM V3 Barrier heights

Isotopologues Natural abundance 3.5 million FIDs ~60 hours JKaKc’’ JKaKc’: 212101 13C(5) 15N(1) 13C(2) 15N(3) 13C(9) 13C(4)

Isotopologues 212101 13C(5) 13C(2) 15N(3) 13C(9) 13C(4) 15N(1) Parent A (MHz) 8992.7577(19) 8814.5950(34) 8992.8292(34) 8792.0771(41) 8915.8124(30) 8926.2758(36) 8992.7437(32) B (MHz) 3600.99260(88) 3600.67394(76) 3590.29489(78) 3600.9494(10) 3552.23184(79) 3548.1874(10) 3487.68205(75) C (MHz) 2604.96652(66) 2589.62579(75) 2599.38524(70) 2587.86700(92) 2572.97585(69) 2571.75085(94) 2545.13599(75) DJ (Hz) 83(33) DJK (kHz) 1.661(79) DK (MHz) 0.09927(47) 0.09164(70) 0.09811(72) 0.0895(10) 0.09575(67) 0.09487(74) 0.09805(67) d1 (Hz) -20.6(78) d2 (Hz) -14.5(40) χaa (MHz) 1.2955(56) 1.301(17) 1.294(20) 1.285(17) 1.297(20) 1.318(20) χbb-cc (MHz) 4.199(11) 4.191(24) 4.198(24) 4.199(26) 4.169(32) 4.189(25) 1.3891(65) 1.384(19) 1.368(22) 1.454(17) 1.379(22) 1.411(20) -5.378(11) -5.401(29) -5.387(35) -5.401(31) -5.346(32) -5.363(25) N 184 21 48 19 54 56 58 σ 11.9 8.2 11.5 12.9 14.3 12.4 13C(5) 13C(2) 15N(3) 13C(9) 13C(4) 212101 15N(1)

Structure rs rm(1) Substitution (rs) and mass weighted (rm(1)) Parameter rs rm(1) B3LYP/ aug-cc-pvtz C(2) C(9) 1.4956(27) 1.4923(18) 1.489  C(2) N(1) 1.317(31) 1.3367(33) 1.366  C(2) N(3) 1.333(37) 1.3289(32) 1.314  C(4) C(5) 1.3653(31) 1.3599(20) 1.364  N(3) C(4) 1.417(35) 1.3735(36) 1.376  N(1) C(5) 1.400(13) 1.4026(35) 1.379    C(9) C(2) N(1) 124.0(30) 124.25(28) 123.42 N(3) C(2) N(1) 113.5(14) 112.04(20) 110.52 N(1) C(5) C(4) 104.93(21) 104.95(13) 105.04 N(3) C(4) C(5) 110.20(47) 110.789(98) 110.43 C(2) N(3) C(4) 106.20 C(9) C(2) N(3) 122.5(31) 123.71(22) 126.05 rs Pcc =1.268428(31) amu Å rm(1)

Internal Rotor JKaKc’’ JKaKc’: 212101 A state E state 38 40 A Intensity / μV

Methyl Rotor fit aug-cc-pvtz A - state XIAM B3LYP-D3 A (MHz) 8992.7577(19) 8892.63(13) 8877.840 B (MHz) 3600.99260(88) 3601.155(27) 3577.692 C (MHz) 2604.96652(66) 2604.780(25) 2591.819 DJ (Hz) 83(33) --- DJK (kHz) 1.57(13) 12(5) DK (kHz) 99.27(47) -79(35) d1 (Hz) -20.6(78) ---- d2 (Hz) -14.5(40) χaa(N1) (MHz) 1.2955(56) χbb-cc(N1) (MHz) 4.199(11) 1.3891(65) -5.378(11) V3 (cm-1) 122.697(19) 109.3 F0 (GHz) 157.675 ε (rad) 2.923(77) δ (rad) 0.07555(36) N 182 41 σ (kHz) 11.5 583 aug-cc-pvtz

4(5)-methylimidazole 378.416 cm-1 Tautomerisation 311.936 cm-1 Brent Harris, PhD Thesis, University of Virginia, 2014.

Experimental methyl V3 barrier heights (cm-1) 311.936 357.6 imidazole 429.3 pyrrole thiazole oxazole 378.416 122.697 477.7 332.03 34.938 251.6 45.0 105.8 258.821 380.5 258.4 isothiazole thiophene furan isooxazole 194.1 62.8 416.2 271.9 Grabow et al. J. Mol. Struct. 2002, 612 (2), 349–356.

2-methylimidazole---argon 2-methylimidazole---H2O 2.48 Å 1.87 Å 162.5º 3.40934(44) Å

2.48 Å 3.40934(44) Å 1.87 Å 162.5º 2-methylimidazole---water 2-methylimidazole---argon Experiment DFT A (MHz) 4238.194(30) 4217.010 2624.74888(46) 2622.092 B (MHz) 1733.7795(15) 1767.912 1348.62429(42) 1375.716 C (MHz) 1240.3115(12) 1258.242 1099.75175(75) 1120.894 DK (MHz) -0.0627(50) -0.026601(20) -0.0441 DJK (kHz) 6.583(72) 24.5996(99) 42.58 DJ (kHz) 0.443(16) 2.4564(63) 2.224 d2 (kHz) -0.2499(16) -0.42 d1 (kHz) -0.134(11) -0.5669(51) -0.65 χzz (MHz) 1.232(14) 1.296 -2.7037(99) -2.801 χxx-yy (MHz) 4.077(37) 4.239 -0.114(21) -0.224 -2.9660(99) -3.213 1.950(11) 2.25 -0.339(34) -0.49 4.746(20) -2.253 σ (kHz) 15.9 18.5 N 172 295

2-methylimidazole---argon 2-methylimidazole---H2O 606505 JKaKc:514505 514505 E A 523413 E A A E Monomer Argon Water A (MHz) 8892.63(13) 2624.721(14) 4234.30(51) B (MHz) 3601.155(27) 1346.6945(86) 1732.573(30) C (MHz) 2604.779(25) 1099.738(12) 1240.247(26) V3 (cm-1) 122.697(19) 123.276(26) 154.08(18) 2-methylimidazole 2-methylimidazole---argon 2-methylimidazole---H2O 606505 16180 MHz 16280 MHz

V3 Barrier XIAM V3(cm-1) 2-methylimidazole---H2O B3LYP-D3/aug-cc-pvtz XIAM V3(cm-1) 2-methylimidazole---H2O 2-methylimidazole---argon 2-methylimidazole

2-methylimidazole Methyl group might inhibit H-bond formation Monomer and 13C and 15N isotopologues observed Water and Argon complexes observed Methyl group internal rotation

Acknowledgements Nick Walker Juliane Heitkämper John Mullaney Graham Cooper Dror Bittner