Pharmaceutics 2018, 10
S1/S11
Supplementary Materials: Solvation and Aggregation of Meta-Aminobenzoic Acid in Water: Density Functional Theory and Molecular Dynamics Study Etienne Gaines and Devis Di Tommaso * School of Biological and Chemical Sciences, Materials Research Institute, Queen Mary University of London, Mile End Road, London E1 4NS, UK;
[email protected] * Correspondence:
[email protected]; Tel.: +44-207-882-6226
Table of Contents 1. GAFF parameters for mABA and mABA± ................................................................................................ 2 mABA ............................................................................................................................................................ 2 mABA± .......................................................................................................................................................... 5 2. Simulations of meta-aminobenzoic acid aqueous solutions .................................................................. 8 3. Convergence of the box cell volume ......................................................................................................... 9 4. Time evolution of the number of pairs ................................................................................................... 10 5. Pairwise interaction matrices of meta-aminobenzoic acid aqueous solutions .................................. 10
Pharmaceutics 2018, 10
S2/S11
1. GAFF parameters for mABA and mABA± mABA Table S1. General AMBER forcefield parameters used to model mABA in GROMACS (topology file). ; MBA_GMX.top created by acpype (Rev: 403) on Thu Jul [ defaults ] ; nbfunc 1
comb-rule 2
[ atomtypes ] ;name bond_type ca ca ha ha nh nh hn hn c c oh oh ho ho o o
gen-pairs yes
mass 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000
charge 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000
9 22:34:48 2015
fudgeLJ fudgeQQ 0.5 0.8333
ptype A A A A A A A A
sigma 3.39967e-01 2.59964e-01 3.25000e-01 1.06908e-01 3.39967e-01 3.06647e-01 0.00000e+00 2.95992e-01
epsilon 3.59824e-01 6.27600e-02 7.11280e-01 6.56888e-02 3.59824e-01 8.80314e-01 0.00000e+00 8.78640e-01
; ; ; ; ; ; ; ;
Amb 1.91 1.46 1.82 0.60 1.91 1.72 0.00 1.66
[ moleculetype ] ;name nrexcl MBA 3 [ atoms ] ; nr type 1 ca 2 ha 3 ca 4 nh 5 hn 6 hn 7 ca 8 ha 9 ca 10 ha 11 ca 12 ha 13 ca 14 c 15 oh 16 ho 17 o
resi 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
[ bonds ] ; ai 1 1 1 3 3 4 4 7 7 9 9 11 11 13 14 14 15
aj funct 2 1 3 1 13 1 4 1 7 1 5 1 6 1 8 1 9 1 10 1 11 1 12 1 13 1 14 1 15 1 17 1 16 1
[ pairs ] ; ai 1 1 1 1 1 1 1 2
aj 5 6 8 9 12 15 17 4
res MBA MBA MBA MBA MBA MBA MBA MBA MBA MBA MBA MBA MBA MBA MBA MBA MBA
atom C2 H2 C1 N1 H5 H6 C6 H1 C5 H4 C4 H3 C3 C7 O2 H7 O1
cgnr 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
r 1.0870e-01 1.3870e-01 1.3870e-01 1.3640e-01 1.3870e-01 1.0140e-01 1.0140e-01 1.0870e-01 1.3870e-01 1.0870e-01 1.3870e-01 1.0870e-01 1.3870e-01 1.4870e-01 1.3060e-01 1.2140e-01 9.7400e-02
funct 1 ; 1 ; 1 ; 1 ; 1 ; 1 ; 1 ; 1 ;
C2 C2 C2 C2 C2 C2 C2 H2
-
charge -0.185783 0.172356 0.297382 -0.890198 0.379769 0.379769 -0.178160 0.160780 -0.218354 0.169120 -0.118964 0.157379 -0.112371 0.773096 -0.641122 0.451189 -0.595890
k 2.8811e+05 4.0033e+05 4.0033e+05 3.7572e+05 4.0033e+05 3.3572e+05 3.3572e+05 2.8811e+05 4.0033e+05 2.8811e+05 4.0033e+05 2.8811e+05 4.0033e+05 2.9263e+05 3.9028e+05 5.4225e+05 3.0928e+05
H5 H6 H1 C5 H3 O2 O1 N1
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
mass 12.01000 1.00800 12.01000 14.01000 1.00800 1.00800 12.01000 1.00800 12.01000 1.00800 12.01000 1.00800 12.01000 12.01000 16.00000 1.00800 16.00000
C2 C2 C2 C1 C1 N1 N1 C6 C6 C5 C5 C4 C4 C3 C7 C7 O2
-
H2 C1 C3 N1 C6 H5 H6 H1 C5 H4 C4 H3 C3 C7 O2 O1 H7
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
; qtot bond_type qtot -0.186 qtot -0.013 qtot 0.284 qtot -0.606 qtot -0.226 qtot 0.153 qtot -0.025 qtot 0.136 qtot -0.082 qtot 0.087 qtot -0.032 qtot 0.125 qtot 0.013 qtot 0.786 qtot 0.145 qtot 0.596 qtot 0.000
0.0860 0.0150 0.1700 0.0157 0.0860 0.2104 0.0000 0.2100
Pharmaceutics 2018, 10 2 2 2 3 3 3 4 4 5 6 7 8 8 9 10 10 11 11 12 13 13 13 16
S3/S11
7 11 14 10 11 14 8 9 7 7 12 10 11 14 12 13 15 17 14 4 7 16 17
1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
[ angles ] ; ai aj 1 3 1 3 1 13 1 13 2 1 2 1 3 1 3 4 3 4 3 7 3 7 4 3 5 4 7 9 7 9 8 7 9 11 9 11 10 9 11 13 12 11 13 14 13 14 14 15 15 14
ak 4 7 11 14 3 13 13 5 6 8 9 7 6 10 11 9 12 13 11 14 13 15 17 16 17
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
H2 H2 H2 C1 C1 C1 N1 N1 H5 H6 C6 H1 H1 C5 H4 H4 C4 C4 H3 C3 C3 C3 H7
funct 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
-
C6 C4 C7 H4 C4 C7 H1 C5 C6 C6 H3 H4 C4 C7 H3 C3 O2 O1 C7 N1 C6 H7 O1
theta 1.2013e+02 1.1997e+02 1.1997e+02 1.2014e+02 1.2001e+02 1.2001e+02 1.1997e+02 1.1613e+02 1.1613e+02 1.2001e+02 1.1997e+02 1.2013e+02 1.1485e+02 1.2001e+02 1.1997e+02 1.2001e+02 1.2001e+02 1.1997e+02 1.2001e+02 1.2014e+02 1.2001e+02 1.1344e+02 1.2344e+02 1.0737e+02 1.2288e+02
[ dihedrals ] ; propers ; treated as RBs in GROMACS to use ; i j k l func 1 3 4 5 0.00000 ; C2C1N11 3 4 6 0.00000 ; C2C1N11 3 7 8 0.00000 ; C2C1C61 3 7 9 0.00000 ; C2C1C61 13 11 9 0.00000 ; C2C3C41 13 11 12 0.00000 ; C2C3C41 13 14 15 0.00000 ; C2C3C71 13 14 17 0.00000 ; C2C3C72 1 3 4 0.00000 ; H2C2C12 1 3 7 0.00000 ; H2C2C12 1 13 11 0.00000 ; H2C2C32 1 13 14
cth 5.8024e+02 5.6216e+02 5.6216e+02 5.4091e+02 4.0551e+02 4.0551e+02 5.6216e+02 4.1070e+02 4.1070e+02 4.0551e+02 5.6216e+02 5.8024e+02 3.3514e+02 4.0551e+02 5.6216e+02 4.0551e+02 4.0551e+02 5.6216e+02 4.0551e+02 5.4091e+02 4.0551e+02 5.8668e+02 5.7463e+02 4.2836e+02 6.4752e+02
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
C2 C2 C2 C2 H2 H2 C1 C1 C1 C1 C1 N1 H5 C6 C6 H1 C5 C5 H4 C4 H3 C3 C3 C7 O2
-
C1 C1 C3 C3 C2 C2 C2 N1 N1 C6 C6 C1 N1 C5 C5 C6 C4 C4 C5 C3 C4 C7 C7 O2 C7
-
N1 C6 C4 C7 C1 C3 C3 H5 H6 H1 C5 C6 H6 H4 C4 C5 H3 C3 C4 C7 C3 O2 O1 H7 O1
combine multiple AMBER torsions per quartet C0 C1 C2 C3 C4 3 8.78640 0.00000 -8.78640 0.00000 H5 3 8.78640 0.00000 -8.78640 0.00000 H6 3 30.33400 0.00000 -30.33400 0.00000 H1 3 30.33400 0.00000 -30.33400 0.00000 C5 3 30.33400 0.00000 -30.33400 0.00000 C5 3 30.33400 0.00000 -30.33400 0.00000 H3 3 8.36800 0.00000 -8.36800 0.00000 O2 3 8.36800 0.00000 -8.36800 0.00000 O1 3 30.33400 0.00000 -30.33400 0.00000 N1 3 30.33400 0.00000 -30.33400 0.00000 C6 3 30.33400 0.00000 -30.33400 0.00000 C4 3 30.33400 0.00000 -30.33400 0.00000
C5 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000
Pharmaceutics 2018, 10 0.00000 3 0.00000 3 0.00000 3 0.00000 3 0.00000 4 0.00000 4 0.00000 5 0.00000 6 0.00000 7 0.00000 7 0.00000 8 0.00000 8 0.00000 9 0.00000 10 0.00000 10 0.00000 11 0.00000 11 0.00000 12 0.00000 13 0.00000 13 0.00000 13 0.00000 16 0.00000
;
S4/S11
H21
;
C213
C11
;
C213
C17
;
C29
C17
;
C69
C13
;
C67
N13
;
C17
N14
;
C13
H54
;
N13
H69
;
N111
C69
;
C511
C67
;
C59
H17
;
C69
H111
;
C613
C59
;
C411
H49
;
C511
H413
;
C514
C413
;
C314
C411
;
C313
H31
;
C43
C31
;
C23
C314
;
C215
C315
;
C714
H7-
O2-
C311 C314 C310 C511 C58 C69 C67 C17 C112 C413 C410 C511 C514 C312 C413 C415 C717 C714 C34 C17 C116 O217 C7-
C7 3 C4 3 C7 3 H4 3 C4 3 H1 3 C5 3 C6 3 C6 3 H3 3 C3 3 H4 3 C4 3 C7 3 H3 3 C3 3 O2 3 O1 3 C7 3 N1 3 C6 3 H7 3 O1
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
8.78640
0.00000
-8.78640
0.00000
0.00000
8.78640
0.00000
-8.78640
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
8.36800
0.00000
-8.36800
0.00000
0.00000
8.36800
0.00000
-8.36800
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
19.24640
0.00000
-19.24640
0.00000
0.00000
27.19600
-7.94960
-19.24640
0.00000
0.00000
[ dihedrals ] ; impropers ; treated as propers in GROMACS to use correct AMBER analytical ; i j k l func phase kd pn 1 7 3 4 1 180.00 4.60240 2 ; 2 1 13 3 1 180.00 4.60240 2 ; 3 5 4 6 1 180.00 4.60240 2 ; 3 9 7 8 1 180.00 4.60240 2 ; 7 11 9 10 1 180.00 4.60240 2 ; 9 13 11 12 1 180.00 4.60240 2 ; 13 17 14 15 1 180.00 43.93200 2 ; 14 1 13 11 1 180.00 4.60240 2 ; [ system ] MBA [ molecules ] ; Compound MBA
nmols 1
function C2H2C1C1C6C5C3C7-
C6C2H5C5C4C3O1C2-
C1C3N1C6C5C4C7C3-
N1 C1 H6 H1 H4 H3 O2 C4
Pharmaceutics 2018, 10
S5/S11
mABA± Table S2. General AMBER forcefield parameters used to model mABA± in GROMACS (topology file). ; ZMB_GMX.top created by acpype (Rev: 403) on Sun Sep [ defaults ] ; nbfunc 1
comb-rule 2
[ atomtypes ] ;name bond_type ca ca ha ha n4 n4 hn hn c c o o
gen-pairs yes
mass 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000
charge 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000
4 21:51:21 2016
fudgeLJ fudgeQQ 0.5 0.8333
ptype A A A A A A
sigma 3.39967e-01 2.59964e-01 3.25000e-01 1.06908e-01 3.39967e-01 2.95992e-01
epsilon 3.59824e-01 6.27600e-02 7.11280e-01 6.56888e-02 3.59824e-01 8.78640e-01
; ; ; ; ; ;
Amb 1.91 1.46 1.82 0.60 1.91 1.66
[ moleculetype ] ;name nrexcl ZMB 3 [ atoms ] ; nr type 1 ca 2 ha 3 ca 4 n4 5 hn 6 hn 7 hn 8 ca 9 ha 10 ca 11 ha 12 ca 13 ha 14 ca 15 c 16 o 17 o
resi 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
[ bonds ] ; ai 1 1 1 3 3 4 4 4 8 8 10 10 12 12 14 15 15
aj funct 2 1 3 1 14 1 4 1 8 1 5 1 6 1 7 1 9 1 10 1 11 1 12 1 13 1 14 1 15 1 16 1 17 1
[ pairs ] ; ai 1 1 1 1 1 1 1 1 2 2 2 2
aj 5 6 7 9 10 13 16 17 4 8 12 15
res ZMB ZMB ZMB ZMB ZMB ZMB ZMB ZMB ZMB ZMB ZMB ZMB ZMB ZMB ZMB ZMB ZMB
atom C2 H2 C1 N1 H5 H6 H7 C6 H1 C5 H4 C4 H3 C3 C7 O2 O1
cgnr 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
r 1.0870e-01 1.3870e-01 1.3870e-01 1.4650e-01 1.3870e-01 1.0330e-01 1.0330e-01 1.0330e-01 1.0870e-01 1.3870e-01 1.0870e-01 1.3870e-01 1.0870e-01 1.3870e-01 1.4870e-01 1.2140e-01 1.2140e-01
funct 1 ; 1 ; 1 ; 1 ; 1 ; 1 ; 1 ; 1 ; 1 ; 1 ; 1 ; 1 ;
C2 C2 C2 C2 C2 C2 C2 C2 H2 H2 H2 H2
-
charge -0.201672 0.168307 0.126418 -0.389661 0.335820 0.335820 0.335820 -0.233164 0.161128 -0.204098 0.174390 -0.057139 0.159004 -0.022851 0.797939 -0.743031 -0.743031
k 2.8811e+05 4.0033e+05 4.0033e+05 2.7246e+05 4.0033e+05 3.0878e+05 3.0878e+05 3.0878e+05 2.8811e+05 4.0033e+05 2.8811e+05 4.0033e+05 2.8811e+05 4.0033e+05 2.9263e+05 5.4225e+05 5.4225e+05
H5 H6 H7 H1 C5 H3 O2 O1 N1 C6 C4 C7
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
mass 12.01000 1.00800 12.01000 14.01000 1.00800 1.00800 1.00800 12.01000 1.00800 12.01000 1.00800 12.01000 1.00800 12.01000 12.01000 16.00000 16.00000
C2 C2 C2 C1 C1 N1 N1 N1 C6 C6 C5 C5 C4 C4 C3 C7 C7
-
H2 C1 C3 N1 C6 H5 H6 H7 H1 C5 H4 C4 H3 C3 C7 O2 O1
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
; qtot bond_type qtot -0.202 qtot -0.033 qtot 0.093 qtot -0.297 qtot 0.039 qtot 0.375 qtot 0.711 qtot 0.478 qtot 0.639 qtot 0.435 qtot 0.609 qtot 0.552 qtot 0.711 qtot 0.688 qtot 1.486 qtot 0.743 qtot 0.000
0.0860 0.0150 0.1700 0.0157 0.0860 0.2100
Pharmaceutics 2018, 10 3 3 3 4 4 5 6 7 8 9 9 10 11 11 12 12 13 14 14
S6/S11
11 12 15 9 10 8 8 8 13 11 12 15 13 14 16 17 15 4 8
1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
[ angles ] ; ai aj 1 3 1 3 1 14 1 14 2 1 2 1 3 1 3 4 3 4 3 4 3 8 3 8 4 3 5 4 5 4 6 4 8 10 8 10 9 8 10 12 10 12 11 10 12 14 13 12 14 15 14 15 16 15
ak 4 8 12 15 3 14 14 5 6 7 9 10 8 6 7 7 11 12 10 13 14 12 15 14 16 17 17
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
C1 C1 C1 N1 N1 H5 H6 H7 C6 H1 H1 C5 H4 H4 C4 C4 H3 C3 C3
funct 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
-
H4 C4 C7 H1 C5 C6 C6 C6 H3 H4 C4 C7 H3 C3 O2 O1 C7 N1 C6
theta 1.1841e+02 1.1997e+02 1.1997e+02 1.2014e+02 1.2001e+02 1.2001e+02 1.1997e+02 1.0852e+02 1.0852e+02 1.0852e+02 1.2001e+02 1.1997e+02 1.1841e+02 1.0811e+02 1.0811e+02 1.0811e+02 1.2001e+02 1.1997e+02 1.2001e+02 1.2001e+02 1.1997e+02 1.2001e+02 1.2014e+02 1.2001e+02 1.2344e+02 1.2344e+02 1.3038e+02
[ dihedrals ] ; propers ; treated as RBs in GROMACS to use ; i j k l func 1 3 4 5 0.00000 ; C2C1N11 3 4 6 0.00000 ; C2C1N11 3 4 7 0.00000 ; C2C1N11 3 8 9 0.00000 ; C2C1C61 3 8 10 0.00000 ; C2C1C61 14 12 10 0.00000 ; C2C3C41 14 12 13 0.00000 ; C2C3C41 14 15 16 0.00000 ; C2C3C71 14 15 17 0.00000 ; C2C3C72 1 3 4 0.00000 ; H2C2C12 1 3 8 0.00000 ; H2C2C12 1 14 12 0.00000 ; H2C2C32 1 14 15
cth 5.6300e+02 5.6216e+02 5.6216e+02 5.4091e+02 4.0551e+02 4.0551e+02 5.6216e+02 3.9781e+02 3.9781e+02 3.9781e+02 4.0551e+02 5.6216e+02 5.6300e+02 3.3907e+02 3.3907e+02 3.3907e+02 4.0551e+02 5.6216e+02 4.0551e+02 4.0551e+02 5.6216e+02 4.0551e+02 5.4091e+02 4.0551e+02 5.7463e+02 5.7463e+02 6.5413e+02
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
C2 C2 C2 C2 H2 H2 C1 C1 C1 C1 C1 C1 N1 H5 H5 H6 C6 C6 H1 C5 C5 H4 C4 H3 C3 C3 O2
-
C1 C1 C3 C3 C2 C2 C2 N1 N1 N1 C6 C6 C1 N1 N1 N1 C5 C5 C6 C4 C4 C5 C3 C4 C7 C7 C7
-
N1 C6 C4 C7 C1 C3 C3 H5 H6 H7 H1 C5 C6 H6 H7 H7 H4 C4 C5 H3 C3 C4 C7 C3 O2 O1 O1
combine multiple AMBER torsions per quartet C0 C1 C2 C3 C4 3 0.00000 0.00000 14.64400 0.00000 H5 3 0.00000 0.00000 14.64400 0.00000 H6 3 0.00000 0.00000 14.64400 0.00000 H7 3 30.33400 0.00000 -30.33400 0.00000 H1 3 30.33400 0.00000 -30.33400 0.00000 C5 3 30.33400 0.00000 -30.33400 0.00000 C5 3 30.33400 0.00000 -30.33400 0.00000 H3 3 8.36800 0.00000 -8.36800 0.00000 O2 3 8.36800 0.00000 -8.36800 0.00000 O1 3 30.33400 0.00000 -30.33400 0.00000 N1 3 30.33400 0.00000 -30.33400 0.00000 C6 3 30.33400 0.00000 -30.33400 0.00000 C4 3 30.33400 0.00000 -30.33400 0.00000
C5 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000 0.00000
Pharmaceutics 2018, 10 0.00000 3 0.00000 3 0.00000 3 0.00000 3 0.00000 4 0.00000 4 0.00000 5 0.00000 6 0.00000 7 0.00000 8 0.00000 8 0.00000 9 0.00000 9 0.00000 10 0.00000 11 0.00000 11 0.00000 12 0.00000 12 0.00000 13 0.00000 14 0.00000 14 0.00000
;
S7/S11
H21
;
C214
C11
;
C214
C18
;
C210
C18
;
C610
C13
;
C68
N13
;
C18
N14
;
C13
H54
;
N13
H64
;
N13
H710
;
N112
C610
;
C512
C68
;
C510
H18
;
C610
H112
;
C614
C510
;
C412
H410
;
C512
H414
;
C515
C414
;
C315
C412
;
C314
H31
;
C43
C31
;
C23
C3-
C2-
C312 C315 C311 C512 C59 C610 C68 C18 C18 C113 C414 C411 C512 C515 C313 C414 C416 C717 C715 C34 C18 C1-
C7 3 C4 3 C7 3 H4 3 C4 3 H1 3 C5 3 C6 3 C6 3 C6 3 H3 3 C3 3 H4 3 C4 3 C7 3 H3 3 C3 3 O2 3 O1 3 C7 3 N1 3 C6
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
0.00000
0.00000
14.64400
0.00000
0.00000
0.00000
0.00000
14.64400
0.00000
0.00000
0.00000
0.00000
14.64400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
8.36800
0.00000
-8.36800
0.00000
0.00000
8.36800
0.00000
-8.36800
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
30.33400
0.00000
-30.33400
0.00000
0.00000
[ dihedrals ] ; impropers ; treated as propers in GROMACS to use correct AMBER analytical ; i j k l func phase kd pn 1 8 3 4 1 180.00 4.60240 2 ; 2 1 14 3 1 180.00 4.60240 2 ; 3 10 8 9 1 180.00 4.60240 2 ; 8 12 10 11 1 180.00 4.60240 2 ; 10 14 12 13 1 180.00 4.60240 2 ; 14 16 15 17 1 180.00 4.60240 2 ; 15 1 14 12 1 180.00 4.60240 2 ; [ system ] ZMB [ molecules ] ; Compound ZMB
nmols 1
function C2H2C1C6C5C3C7-
C6C2C5C4C3O2C2-
C1C3C6C5C4C7C3-
N1 C1 H1 H4 H3 O1 C4
Pharmaceutics 2018, 10
S8/S11
2. Simulations of Meta-Aminobenzoic Acid Aqueous Solutions Table S3. Details of molecular dynamics simulation.
1 2 3 4 5 6 7
Method
no. of mABA molecules
AIMD AIMD CMD CMD CMD CMD CMD
1 4 8 16 32 64
no. of mABA+ molecules 1 4 8 16 32 64
no. of H2O molecules 210 215 11385 11230 11123 11101 11101
Box length (Å) 18.65 18.70 69.89 69.69 69.75 69.95 70.67
Conc. (mol/L)
Simulation time (ps)
0.26 0.25 0.04 0.08 0.16 0.31 0.60
20 20 400000 200000 200000 200000 200000
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3. Convergence of the Box Cell Volume
Figure S1. Convergence of the volume of the two simulation boxes containing one mABA and one mABA± in water.
Figure S2. Convergence of the volume of the simulation boxes containing mixed mABA– mABA± solutions.
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4. Time Evolution of the Number of Pairs
(a)
(b)
Figure S3. Time evolution of the number of pairs between meta-benzoic acid molecules in mixed mABA–mABA± aqueous solutions computed during the last 40 ns of the MD simulations: (a) 0.16 mol L-1; (b) 0.31 mol L-1. 5. Pairwise Interaction Matrices of Meta-Aminobenzoic Acid Aqueous Solutions Table S4. Matrix elements of the pairwise interaction matrix for the mixed 0.04 mol L-1 mABA– mABA± aqueous solutions. Values of expressed as percentage. A* B* C* A B C
A* 0.2
B* 0.5 9.4
C* 7.7 2.4 0.1
A 2.0 0.7 1.9 6.5
B 1.9 5.7 0.5 4.7 11.8
C 2.7 5.7 3.9 7.7 15.7 8.5
Table S5. Matrix elements of the pairwise interaction matrix for the mixed 0.16 mol L-1 mABA– ± mABA aqueous solutions. Values of expressed as percentage. A* B* C* A B C
A* 0.2
B* 0.9 12.8
C* 9.3 3.3 0.3
A 4.1 2.4 3.7 5.0
B 3.3 8.1 1.9 3.7 6.6
C 3.6 6.6 3.0 6.4 9.1 5.6
Table S6. Matrix elements of the pairwise interaction matrix for the mixed 0.31 mol L-1 mABA– ± mABA aqueous solutions. Values of expressed as percentage. A* B* C* A
A* 0.3
B* 0.7 9.8
C* 9.3 2.8 0.3
A 4.6 2.2 3.7 5.9
B 3.5 7.8 1.7 4.0
C 3.9 6.9 3.8 6.3
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B C
6.5
9.7 6.6
Figure S4. Intermolecular distances between the amino (NH2 and NH3+), carboxylic (COOH and COO–), and benzine (C6H4) groups in the most thermodynamically stable (mABA)2, (mABA)(mABA±) and (mABA±)2 dimers in water.
