Concluding Remarks

Exactness and reproducibility of chromatographic Ru data strictly depends on the application of standardized experimental conditions. Control of temperature and humidity, the use of front markers, the densitometric evaluation of starting and running points and the extrapolation to modifier-free conditions deserve mention here. Provided theTLC data are obtained under these experimental conditions they represent an attractive alternative to the tedious and time-consuming measurement of partition coefficients.

Important advantages of TLC are inter alia that test compounds need not be pure and that only trace amounts of test material are necessary. Compounds can be investigated over a broad lipophilicity range and a quantitative determination of their concentration (often posing analytical problems) is not necessary.

Also in comparison with RP-HPLC we view RP-TLC as a feasible alternative. One of the major advantages of RP-TLC is its speed. As described previously [24], 30 compounds can be tested simultaneously. This number can even be increased by double use of at least some starting positions. One only has to guarantee that the compounds sharing a starting position should differ in lipophilicity by at least one log unit which can easily be determined ahead of time by calculating their Xf or CLOGP values.

Another advantage of lipophilicity determination by TLC might be the somewhat broader range of measurable lipophilicities. According to Braumann [27] this measurable range comprises log /cw values from 0.0 to 7.0 in the case of RP-HPLC, while the range in the case of RP-TLC includes RM„ values from about -1.0 to + 7.0.

An important disadvantage of TLC is its lack of applicability to liquid test compounds except those with a very high boiling point.

Taken together, from the authors' point of view TLC represents a convenient experimental alternative to RP-HPLC and octanol/water partitioning for measurement of molecular lipophilicity and application in QSAR studies. Table 5 summarizes some illustrative examples for successful applications of TLC data in QSAR. Additional examples are given by Tomlinson [18].

Table 8.5. Application of RP-TLC in QSAR studies

Compounds

Biological activity

References

Cardiac glycosides

Inhibition of Na-K-ATPase

[58]

Cardiac glycosides

Positive inotropic action

[71]

Dihydropyridines

Binding to Ca-channels

[73]

Dihydropyridines

Negative inotropic action

[74]

Phosphothionates

Fungicidal activity

[75]

Sulfonamides

Antimalarial activity

[78]

Benzodiazepines

Behavioral activity

[79]

Arylaliphatic acids

Fibrinolytic and antihemolytic activity

[80]

Acridines

Antitumor activity

[81, 82]

Bis-guanyl-hydrazones

Antileukemic activity

[83]

Heteroatomic hydrocarbons

Activity of Photobacter phosphorus

[32]

Heteroatomic hydrocarbons

Toxicity in Poeciliea reticulata

[32]

Table 8.5. Continued

Compounds

Biological activity

References

Heteroatomic hydrocarbons

Toxicity in Daphnia magna

[32]

Phenols

Toxicity in rats

[23]

Phenols

Toxicity in guppies

[23]

Phenols

Toxicity in Daphnia magna

[23]

Benzoic acids

Toxicity in mosquito larvae

[21]

Naphthols

Toxicity in chick embryo

[76]

Nitro-imidazoles

Biliary excretion

[77]

Class I antiarrhythmics

Therapeutic dose in humans

[72]

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