Utvrđivanje veze između strukture i retencije oksotiazolidina primenom multivarijantne analize
Quantitative structure-retention relationship study of oxothiazolidines using multivariate analysis
Author
Dabić, DraganaMentor
Tešić, Živoslav
Committee members
Natić, Maja M.
Milojković-Opsenica, Dušanka

Agbaba, Danica

Baranac-Stojanović, Marija

Metadata
Show full item recordAbstract
Hromatografsko ponašanje 23 novosintetisana 2-alkiliden-4-oksotiazolidina
ispitivano je u uslovima reverzno-fazne planarne hromatografije, uz upotrebu dve
stacionarne faze (oktadecil-modifikovan (RP-18) i cijano-modifikovan (CN) silika-gel).
Dvokomponentne smeše methanol/voda, acetonitril/voda i tetrahidrofuran/voda su
korišćene kao mobilne faze. Linearna zavisnost RM vrednosti od zapreminskog udela
organske komponente u mobilnoj fazi utvrđena je za sva ispitivana jedinjenja, sa
visokom vrednošću korelacionog koeficijenta (r > 0,99).
Ispitivani 4-oksotiazolidini predstavljaju kongenernu seriju jedinjenja, što
potvrđuje značajan nivo korelacije dobijen pri poređenju RM
0 vrednosti i drugih
hromatografskih parametara (m, C0 i PC1). Svi hromatografski parametri lipofilnosti
(RM
0, m, C0 i PC1) poređeni su sa izračunatim log P vrednostima. Statistički parametri
ovih zavisnosti pokazali su da RM
0 vrednosti mnogo pouzdanije opisuju lipofilnosti od
preostalih hromatografskih parametara (m, C...0 i PC1).
Analiza glavnih komponenata je primenjena na retencione podatke u cilju
utvrđivanja sličnosti i razlika između upotrebljenih hromatografskih sistema. Višestruka
linearna regresija (MLR) i parcijalna regresija najmanjih kvadrata (PLS) su omogućile
ispitivanje odnosa između molekulskih deskriptora ispitivanih N-supstituisanih
2-alkiliden-4-oksotiazolidina i retencionih podataka određenih primenom dva
hromatografska sistema (tetrahidrofuran/voda na RP-18 i CN stacionarnoj fazi).
Potpuna geometrijska optimizacija izvršena je pomoću AM1 semi-empirijske
molekulsko-orbitalne metode, nakon čega je set fizičko-hemijskih molekulskih
deskriptora izračunat iz optimizovanih struktura.
Poređenjem statističkih parametara odabran je model gde je na najbolji način
opisana veza između seta izračunatih deskriptora i RM
0 vrednosti. Dobra prediktivna
moć MLR i PLS modela dobijenih za kalibracioni set podataka potvrđena je na
podacima iz test seta. Molekulski deskriptori uključeni u odabrane MLR i PLS modele
su slične prirode, a u sve dobijene modele uključen je parametar lipofilnosti (log P) što
ukazuje na značaj lipifilnosti i njen uticaj na retenciju N-supstituisanih 2-alkiliden-4-
oksotiazolidina.
The chromatographic behavior of 23 new 2-alkylidene-4-oxothiazolidine
derivates was investigated by means of the reversed-phase thin-layer chromatography
(RP TLC) on RP-18 and CN stationary phases. Binary mixtures of methanol/water,
acetonitrile/water and tetrahydrofuran/water were used as mobile phases. Linear
relationships between the volume fraction of the organic mobile phase modifier and the
RM values were established for each solute with the high correlation coefficient values
(r > 0.99).
The investigated 4-oxothiazolidines are a congeneric set of compounds, and
significant correlations were obtained between the chromatographically determined RM
0
and other retention parameters (m, C0, and PC1). All lipophilicity parameters (RM
0, m,
C0, and PC1) obtained from the reversed-phase experiments were compared with the
calculated log P values. Statistical parameters of these correlations showed that RM
0
values were more suitable for lipophilicity estimation than other retention parame...ters
(m, C0, and PC1).
Principal Component Analysis was performed on retention data in an attempt to
reflect the similarities and differences among different chromatographic systems.
Multiple linear regression (MLR) and partial least squares regression (PLS) were
performed to investigate relation between the structural descriptors of N-substituted
2-alkylidene-4-oxothiazolidines and chromatographic retention determined for the two
chromatographic systems (tetrahydrofuran/water on RP-18 and CN stationary phases).
Full geometry optimization based on Austin Model 1 (AM1) semiempirical molecular
orbital method was carried out and a set of physicochemical molecular descriptors was
calculated from the optimized structures.
The best relationships in a set of calculated descriptors and RM
0 values were
chosen on the basis of comparison of the statistical parameters. The statistical
parameters of MLR and PLS models built for training set show a significant predictive
ability. The descriptors included in the chosen MLR and PLS models were of similar
nature. Lipophilicity parameter (log P) selected out of a large set of possible molecular
descriptors in all models, indicated the importance of lipophilicity and its influence on
the retention behavior of the N-substituted 2-alkylidene-4-oxothiazolidines.
Faculty:
Универзитет у Београду, Хемијски факултетDate:
08-07-2013Projects:
- Structure-properties relationships of natural and synthetic molecules and their metal complexes (RS-172017)