The Conformational Landscape of Serinol M. E. Sanz, D. Loru, Department of Chemistry, King’s College London, UK I. Peña, J. L. Alonso Grupo de Espectroscopía Molecular Universidad de Valladolid, Spain

Motivation Serinol Conformational investigation b-amino alcohols: vicinal amino and alcohol groups Great variety of intra- and intermolecular hydrogen bonds b-amino alcohols derived from a-amino acids are used in the synthesis of enantiomerically pure bioactive compounds Hydrophilic head of sphingosine sphingosine Constituent of artificial nucleic acids better understanding of stereocontrol Conformational investigation molecular recognition, self assembly

Chirped Pulse FTMW Spectroscopy S. Mata et al., J. Mol. Spectrosc. 280, 91 (2012) I. Peña et al., Phys. Chem. Chem. Phys. 15, 18243 (2013)

Serinol Rotational Spectrum: CP-FTMW * * photofragmentation lines

Rotational Spectrum

Serinol ga gG gg aa ag Gg > 200 conformers Families of conformers O4-C1-C2-C3 C1-C2-C3-O5 ga gG gg OH OH OH OH NH2 NH2 NH2 g  -60 G  +60 a  180 OH OH aa ag Gg NH2 NH2 NH2 OH OH OH OH OH OH

Computational > 200 conformers Lowest-energy conformers? Semiempirical and ab initio calculations 1. AM1 method ~ 70 conformers within 25 kJ/mol 2. MP2/6-311++G(d,p) Geometry optimizations and vibrational frequency calculations

Computational ga gG aa Gg ag gg Families of conformers 22 conformers within 1000 cm-1 Families of conformers ga gG aa Gg ag gg MP2/6-311++G(d,p)

Serinol Assignment and Identification

Serinol Assignment and Identification ga1 ga2 11,0 ← 00,0 2 ← 1 F′ ← F′′ = 2 ← 1 1 ← 1 1 ← 1 0 ← 1 0 ← 1 ga1 ga2

Serinol Assignment and Identification

Serinol Assignment and Identification Intense c-type transitions

Serinol Assignment and Identification a-type transitions b-type transitions c-type transitions ~ 600 kHz splitting no splitting no splitting 21,2 ← 11,1 21,2 ← 10,1 21,1 ← 10,1 3 ← 2 3 ← 2 3 ← 2 0+ 0- 2 ← 1 2 ← 1 2 ← 1 0- 1 ← 0 1 ← 0 1 ← 0 0+ 0+ 0- 2 ← 2 1 ← 1 2 ← 2 1 ← 1

Serinol Assignment and Identification a-type transitions b c a-type transitions Conformer which tunnels between two equivalent configurations ~ 600 kHz splitting 21,2 ← 11,1 Small splittings motion of hydrogen atoms 3 ← 2 0+ 0- 2 ← 1 Inversion of ma dipole moment component with tunneling motion 0- 1 ← 0 0+ 0+ 0-

Serinol Assignment and Identification a-type transitions b c a-type transitions ~ 600 kHz splitting 21,2 ← 11,1 3 ← 2 0+ 0- 2 ← 1 0- 1 ← 0 glycerol 0+ 0+ 0- Ilyushin, Moltyenko, Lovas, Plusquellic, J. Mol. Spectrosc. 251, 129 (2008)

Serinol Assignment and Identification Similar intensities of a- and b-type transitions c-type transitions ~ 10 times weaker

Serinol Intramolecular interactions O−H···O O−H···N N−H···O O−H···N

ga1 > gG1 > ga2 ≈ aa1 > ag1 Serinol Relative abundances ga1 > gG1 > ga2 ≈ aa1 > ag1 E ag1 20:6:3:3:1 aa1 ga2 gG1 ga1 MP2/6-311++G(d,p) Gibbs energies 0 cm-1 115 cm-1 159 cm-1 231 cm-1 495 cm-1

Serinol Lower-energy conformers MP2/6-311++G(d,p) DG298 (cm-1)

Serinol Conformational relaxation?

Serinol Conformational relaxation ga family ga1 ga3 ga4 ga2 E/cm-1 HOCC E/cm-1 ga4 ga2 HOCC

Serinol Conformational relaxation aa family E/cm-1 aa3 aa1 aa2 HOCC

Serinol Conclusions Five conformers of serinol identified from the analysis of the rotational spectrum Stabilised by intramolecular hydrogen bonds All conformations very close in energy Behaviour similar to threoninol Vaquero-Vara et al., J.Phys.Chem. A (2014) ASAP serinol gG serinol ag serinol ag serinol aa

Thank you for your attention Acknowledgements Donatella Loru Isabel Peña Santiago Mata Carlos Cabezas José L. Alonso Agustín Martín Lucie Kolesnicová Celina Bermúdez Susana Blanco Juan Carlos López Funding Thank you for your attention