Biomedical Engineering Reference
In-Depth Information
Table 1
Log
P
and SMILES code of tropane alkaloids used in LC-MS-based analysis
Log
P
a
Analyte p
K
b
b
SMILES code
a
−2.93 MeS n.c. C[N+]2(C)C4CC(OC(=O)C(CO)c1ccccc1)CC2C3OC34
−2.06 Cim n.c. C[N+]3(CC1CC1)C5CC(OC(=O)C(CO)c2ccccc2)
CC3C4OC45
−1.94 Tio n.c. C[N+]3(C)C5CC(OC(=O)C(O)(c1cccs1)c2cccs2)CC3C4OC45
−1.49 BuS n.c. CCCC[N+]2(C)C4CC(OC(=O)C(CO)c1ccccc1)CC2C3OC34
−1.47 Ipra n.c. CC(C)[N+]1(C)C3CCC1CC(OC(=O)C(CO)c2ccccc2)C3
−0.61 Tros n.c. OC(C(=O)OC1CC2CCC(C1)[N+]23CCCC3)(c4ccccc4)
c5ccccc5
0.64 Adi 6.82 CN2C3CC(OC(=O)C(O)(CO)c1ccccc1)CC2C4OC34
0.85 Ada 6.08 CN1C3CC(O)C1CC(OC(=O)C(CO)c2ccccc2)C3
1.05 Scp 6.78 CN2C3CC(OC(=O)C(CO)c1ccccc1)CC2C4OC34
1.77 Atr 5.08 CN1C3CCC1CC(OC(=O)C(CO)c2ccccc2)C3
1.77 Hyo 5.08 CN1C3CCC1CC(OC(=O)C(CO)c2ccccc2)C3
1.79 Hatr 5.10 CN1C3CCC1CC(OC(=O)C(O)c2ccccc2)C3
2.13 Lit 5.08 CN1C3CCC1CC(OC(=O)C(O)Cc2ccccc2)C3
2.24 Sat 6.80 CN2C3CC(OS(=O)(=O)c1ccc(C)cc1)CC2C(OC(C)=O)C3
2.43 Gran 4.72 CN1C4CCCC1CC(NC(=O)c2nn(C)c3ccccc23)C4
2.72 Trop 4.76 CN1C4CCC1CC(OC(=O)c2c[nH]c3ccccc23)C4
2.87 Coc 6.49 COC(=O)C2C(OC(=O)c1ccccc1)CC3CCC2N3C
4.19 Beme 5.03 CN1C3CCC1CC(OC(=O)c2cc(Cl)cc(Cl)c2)C3
4.27 Benz 4.88 CN1C4CCC1CC(OC(c2ccccc2)c3ccccc3)C4
For abbreviation of analyte names see Sect. “Abbreviations”.
log P
logarithm of octanol/water
partition coef fi cient;
n.c.
not calculable as N-atom of tropane moiety is present as alkylated quater-
nary amine,
pK
b
negative decadal logarithm of base constant,
SMILES
simpli fi ed molecular input
line entry system
a
Determined and calculated by the molinspiration software after drawing the chemical structure
[
25
]
b
p
K
b
= 14 − p
K
a
, p
K
a
was calculated by SPARC software based on SMILES code for hydrolysis of
protonated N-atom of the tropane moiety [
26
]
influenced by the acid-base equilibrium and thus by pH. Due to optimum extract-
ability from alkaline media, TA were historically classified as alkaloids.
In contrast to TTA, QTA possess a fourfold alkylated N-atom within the tropane
moiety and therefore a permanent positive charge (ammonium cation), e.g.
N-
methyl
scopolamine and
N-
butyl scopolamine, tiotropium, cimetropium, ipratropium and
trospium (Fig
1
). Accordingly, p
K
b
values cannot be calculated. Again, the charge
influences pharmacological properties like distribution in vivo thus preventing the
passage of the blood-cerebrospinal fluid or blood-brain barrier. Furthermore, the
permanent charge of QTA is independent of pH and causes highly polar compounds
with minimum tendency to be transferred into organic non-polar solvents. Therefore,
special attention has been paid to the development of appropriate LLE procedures for
QTA leading to the modification of ion-pair LLE as presented in the Sect.
3.1
[
23,
24
] .
The positive charge of QTA and the explicit proton affinity of TTA make these
cationic compounds ideal candidates for mass spectrometric detection after positive
electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI).
