Supporting Information
Salts and cocrystals of Theobromine and their phase transformations in water
PALASH SANPHUI and ASHWINI NANGIA*
School of Chemistry, University of Hyderabad, Prof. C. R. Rao Road, Gachibowli, Central University
P.O., Hyderabad 500 046, India
Table S1. Hydrogen bonds in crystal structures (neutron-normalized distances).
Crystal forms
+
TBRH Cl
–
TBRH+(PHP)3–
TBRH+(PHP)2.5–
TBRH+MES–
Interaction
H···A /Å
D···A /Å
D–H···A /º
Symmetry code
N2−H2···Cl1
O3−H3B···O1
N4−H4···Cl1
C5−H5···O3
C6−H6A···O3
N1−H1···O1
O3−H3···O8
O4−H4···O6
N4−H4A···O2
O7−H7···O5
O9−H9···O12
O10−H10···O12
O11−H11···O5
O13−H13···O8
O14−H14···O6
C5−H5···O1
C6−H6B···O2
C6−H6B···O3
C6−H6C···O10
C7−H7A···O7
C7−H7C···O13
N1−H1···O2
O3−H3A···O8
N4−H4A···O8
O4−H4A···O11
O6−H6D···O1
O7−H7D···O7
O9−H9···O11
O10−H10···O5
O12−H12···O5
C6−H6A···O12
C6−H6B···O2
C6−H6C···O4
N1−H1···O1
2.04
2.15
2.15
2.30
2.37
1.99
1.65
1.70
1.71
1.59
1.60
1.56
1.58
1.61
1.56
2.31
2.52
2.49
2.51
2.46
2.41
1.83
1.59
1.66
1.57
1.83
1.40
1.60
1.62
1.70
2.50
2.43
2.34
1.95
3.049(4)
2.908(6)
3.156(3)
3.223(6)
3.337(7)
2.957(3)
2.605(2)
2.668(2)
2.652(2)
2.550(2)
2.556(3)
2.525(3)
2.549(3)
2.586(3)
2.531(3)
3.336(3)
3.148(3)
3.259(3)
3.205(3)
3.267(3)
3.457(3)
2.835(4)
2.533(3)
2.655(4)
2.543(4)
2.549(4)
2.379(4)
2.573(3)
2.572(4)
2.677(3)
3.131(4)
3.341(4)
3.396(5)
2.848(5)
178
132
174
142
147
160
164
167
154
165
164
165
169
175
169
158
116
127
121
130
162
171
160
169
169
127
180
171
162
171
116
141
163
168
1/2-x,1-y,1/2+z
1/2+x,1/2-y,1/2-z
-x,-1/2+y,1-z
x,y,1+z
x,y,1+z
1-x,1-y,1-z
1-x,-y,1-z
-x,-y,1-z
1/2-x,-1/2+y,1/2-z
1/2+x,1/2-y,-1/2+z
-1/2+x,1/2-y,-1/2+z
3/2-x,-1/2+y,1/2-z
1/2+x,1/2-y,-1/2+z
1/2-x,1/2-y,3/2-z
1+x,y,z
-1/2+x,1/2-y,-1/2+z
Intramolecular
1/2-x,1/2+y,1/2-z
1/2-x,1/2+y,1/2-z
1/2+x,1/2-y,-1/2+z
-1/2+x,1/2-y,-1/2+z
-x,2-y,-z
1/2-x,-1/2+y,1/2-z
1/2-x,3/2-y,1-z
x,-1+y,z
x,-1+y,z
Intramolecular
1/2-x,-1/2+y,1/2-z
1/2-x,-1/2+y,1/2-z
x,y,z
-x,1-y,-z
-x,1-y,-z
-x,1-y,-z
1-x,1-y,-z
S1
Form I
TBRH+MES–
Form II
TBRH+BES–
TBRH+TOS–
N4−H4···O3
C5−H5···O5
C6−H6B···O2
C6−H6A···O5
N1−H1···O1
N3−H3···O3
C5−H5···O4
C6−H6A···O4
C6−H6A···O5
C6−H6C···O2
C7−H7C···O3
C8−H8B···O1
C8−H8C···O5
N1−H1···O5
N4−H4···O3
C5−H5···O2
C6−H6A···O1
C7−H7B···O4
C9−H9 ···O3
N2−H2···O3
N4−H4···O2
C5−H5···O4
C6−H6A···O5
C7−H7B···O1
C9−H9 ···O3
1.78
2.19
2.61
2.61
1.97
1.63
2.24
2.48
2.42
2.51
2.47
2.29
2.39
1.82
1.65
2.12
2.35
2.34
2.49
1.63
1.83
2.07
2.44
2.32
2.48
2.777(5)
3.176(6)
3.056(6)
3.544(6)
2.937(4)
2.623(4)
3.194(4)
3.437(4)
3.416(5)
3.353(5)
3.260(4)
3.338(5)
3.396(5)
2.823(4)
2.656(4)
3.156(4)
3.412(5)
2.775(4)
2.902(4)
2.631(4)
2.833(4)
3.109(4)
3.503(4)
2.768(4)
2.902(4)
(a)
S2
164
149
104
143
161
168
146
147
153
134
129
161
153
172
173
160
165
102
101
175
172
161
168
103
102
-1+x,1+y,z
x,-1+y,z
x, 3/2-y, -1/2+z
x,-1+y,z
1/2-x,1/2+y,1/2-z
-1/2+x,-1/2+y,z
1/2-x,1/2-y,-z
1/2-x,1/2-y,-z
1/2-x,1/2-y,-z
1/2-x,3/2-y,-z
-1/2+x,-1/2+y,z
1/2-x,-1/2+y,1/2-z
x,1+y,z
1-x,-y,1-z
1/2+x,1/2-y,-1/2+z
5/2-x,-1/2+y,1/2-z
5/2-x,-1/2+y,1/2-z
Intramolecular
Intramolecular
1-x,1-y,1-z
-1-x,-y,1-z
1-x,1-y,1-z
1-x,1-y,1-z
Intramolecular
Intramolecular
(b)
(c)
S3
(d)
(e)
S4
(f)
(g)
(h)
S5
(i)
(j)
Figure S1. Experimental PXRD profile (black trace) comparison with the calculated X-ray lines from
the X-ray crystal structure (red trace) of (a) TBR, (b) TBR.HCl.H2O, (c) TBR.(PHP)2.5, (d) TBR.MES
form II, (e) TBR.BES and (f) TBR.TOS. PXRD comparisons (red trace) of reported cocrystals with
the calculated X-ray lines from the cocrystal structure (blue trace) of (g) TBR–malonic acid, (h)
TBR–gallic acid dihydrate, (i) TBR–5-Cl salicylic acid, and (j) TBR–anthranilic acid. An exact
overlay of PXRD line indicates bulk phase purity.
S6
(a)
(b)
Figure S2. FT-IR spectra comparison of Theobromine salts. The peak at 1700-1730 cm–1 confirm
formation of the salt.
S7
(a)
(b)
S8
(c)
(d)
S9
(e)
(f)
Figure S3. PXRD comparison of TBR salts and reported cocrystal structures after 1 h slurry in water
with the calculated X-ray lines of TBR salts/cocrystals and TBR indicates phase transformation to
theobromine within this short time period.
S10