The Comparison of Mw with Calculated log P

Recently, computerized calculations of log P have attracted increasing interest as substitutes for experimental approaches. According to the methodology applied calculation procedures can be classified into fragmentai methods (2f, CLOGP), atom-based (CHEMICALC, SMILOGP, HINT) and molecular property-based approaches (ASCLOGP). For a detailed treatise the reader is referred to Chapter 23 of this volume.

For two test sets of 92 simple, rather homogeneous organic standard compounds and 68 chemically quite diverse drug molecules, we have correlated RMv, data with calculated log P representing the three calculation procedures mentioned above. The results are summarized in Table 4. These calculations substantiate the better fit between chromatographic and partitioning data in the case of homogeneous as compared to chemically heterogeneous compounds. In addition, for both test sets fragmentai calculation procedures exhibit higher interrelations with RMw data than atom - or molecular property - based procedures.

Table 8.4. /?Mw = a + b log Pc!k,c. Correlations of RP-TLC data (R\U) with calcuated otanol/wa-ter partition coefficients (log Pxt) are listed. Atom-based (CHEMICALC-2, HINT) and fragmentai calculation approaches (Zf, CLOGP 4.34, KLOGP) were included. In general, the interrelation is better for simple organic standard compounds than for complicated drug molecules (included compounds are in detail given in Chapter 23 of this volume).

Table 8.4. /?Mw = a + b log Pc!k,c. Correlations of RP-TLC data (R\U) with calcuated otanol/wa-ter partition coefficients (log Pxt) are listed. Atom-based (CHEMICALC-2, HINT) and fragmentai calculation approaches (Zf, CLOGP 4.34, KLOGP) were included. In general, the interrelation is better for simple organic standard compounds than for complicated drug molecules (included compounds are in detail given in Chapter 23 of this volume).

Calculation method

a

b

r

n

Organic standard compounds

Zf

0.01

0.91

0.959

92

CLOGP 4.34

0.00

0.93

0.960

90

KLOGP

-0.05

1.00

0.959

90

CHEMICALC 2

0.24

0.89

0.959

92

HINT

0.52

0.77

0.912

91

Drug molecules

Zf

1.18

0.66

0.834

65

CLOGP 4.34

0.95

0.72

0.911

56

KLOGP

0.71

0.75

0.836

67

CHEMICALC 2

1.87

0.58

0.803

68

HINT

1.29

0.59

0.823

65

Was this article helpful?

0 0

Post a comment