Supporting information for:

Exploration of the Theobromine-Water Dimer: Comparison with DNA Microhydration Imanol Usabiagaa,b, Ander Camiruagaa, Camilla Calabrese,a,b Antonio Velosoa, Viola C. D’melloc, Sanjay Wategaonkarc, and Jose A. Fernandez*a a) Dep. of Physical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa 48940, Spain. b) Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country, Leioa, E-48940, Spain. c) Dep. of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India * E-mail: josea.fernandez@ehu.es

Electronic Supplementary Material (ESI) for Physical Chemistry Chemical Physics.This journal is © the Owner Societies 2020

Figure S1: Optimized structures of theobromine·water dimer at the M06-

2x/6-311++G(d,p) level of theory. Dimers are organized in families depending

on their interaction. Reorganization of structures with a water molecule in a

stacked position is also shown. The leading interaction in NHB_08 and 09

takes place between Ow and one of the two methyl groups and therefore it is

intrinsically weak.

Table S1: Binding free energies of various conformers of theobromine·water complex. Values include ZPE and BSSE corrections

LABEL

M062x/6-311++G(d,p) B3LYP/def2tzvp ED=GD3BJ

G (0K) (kJ/mol)

G (298K) (kJ/mol)

G (0K) (kJ/mol)

G (298K) (kJ/mol)

RMSD (NO H ATOMS)

1THEOB+W_2HO_01 -31.6 19.6 -31.3 16.5 0.01

1THEOB+W_2HO_02 -29.0 25.2 -30.6 17.1 0.01

1THEOB+W_HO_03 -26.5 25.2 -26.6 17.7 0.40

1THEOB+W_HO_04 -23.6 26.1 -22.5 18.9 0.28

1THEOB+W_HN_05 -20.4 28.3 -21.3 21.4 0.17

1THEOB+W_HN_06 -19.2 29.4 -21.3 21.4 0.51

1THEOB+W_OTHER_07 -11.3 38.4

1THEOB+W_OTHER_08 -6.4 34.6

1THEOB+W_OTHER_09 -1.1 40.9

Structures in Figure S4

1THEOB_C2_OH+W -49.3 0.8

1THEOB_C6_OH+W -47.8 7.1

Figure S2: REMPI spectra of theobromine monomer and theobromine·water complex. The spectrum of the dimer could not be recorded in the 35100-36100 cm-1 interval due to the stronger signal of theobromine. The two traces of the spectrum of theobromine-water are not scaled. The

wavelength marked with the blue arrow was used to tune the UV laser and record the IR/UV spectrum. This point far to the blue of the 000 transition

was chosen to ensure that the spectral features due to all possible isomers of theobromine-water could be recorded.

Figure S3: Comparison between the experimental RIDIRS spectrum for theobromine·water complex with the computational simulations at two theory levels: M062x/6-311++G(d,p) and B3LYP/def2tzvp ED=GD3BJ2.

Figure S4: Tautomerization of theobromine isomers and the isomerization of the enol forms at M06-2x/6-311++G(d,p) theory level.