PMID- 22917979
OWN - NLM
STAT- MEDLINE
DCOM- 20130311
LR  - 20211021
IS  - 1873-3778 (Electronic)
IS  - 0021-9673 (Print)
IS  - 0021-9673 (Linking)
VI  - 1269
DP  - 2012 Dec 21
TI  - A molecular model of the enantioselective liquid chromatographic separation of 
      (R,S)-ifosfamide and its N-dechloroethylated metabolites on a teicoplanin aglycon 
      chiral stationary phase.
PG  - 218-25
LID - S0021-9673(12)01221-6 [pii]
LID - 10.1016/j.chroma.2012.08.019 [doi]
AB  - The enantioselective separations of the chiral oxazaphosphorines (R,S)-ifosfamide 
      (IF), (R,S)-2-N-dechloroethyl-IF (2-DCE-IF) and (R,S)-3-N-dechloroethyl-IF 
      (3-DCE-IF) were achieved on teicoplanin-based chiral stationary phase using 
      isopropanol:methanol (60:40, v/v) as the mobile phase. Computational models of 
      the teicoplanin and teicoplanin aglycon (TAG) chiral selectors were constructed 
      and used in docking experiments to examine the chiral recognition mechanism 
      associated with the observed resolutions. Initial data showed no significant 
      differences between the simulated selector-selectand complexes using teicoplanin 
      and TAG, and the full study was conducted using TAG. The data from the study 
      indicate that hydrophobic interactions arise between the chlorine atom present in 
      the cholorethyl moieties of the oxazaphosphorine molecules and hydrophobic 
      pockets within the TAG basket and that these interactions anchored and positioned 
      the selectands within the selector-selectand complexes. The complexes were 
      stabilized through the formation of a network of hydrogen bond and cation-pi 
      interactions, in which the latter involved the phosphorous atom of the 
      phosphoramide moiety and aromatic components of the TAG aglycon basket. The 
      chirality of the oxazaphosphorine molecule determined the number and strength of 
      the stabilizing interactions which resulted in significant differences in the 
      relative mean binding energies between the complexes formed by the (R) and (S) 
      enantiomers of the selectands. These differences were consistent with the 
      observed chromatographic enantioselectivity and suggest a multi-step chrial 
      recognition mechanism involving the tethering of the selectand to the selector 
      followed by conformational adjustments and stabilization of the 
      selectand-selector complex.
CI  - Published by Elsevier B.V.
FAU - Ravichandran, Sarangan
AU  - Ravichandran S
AD  - Advanced Biomedical Computing Center, Information Systems Program, SAIC-Frederick 
      Inc., Frederick National Laboratory for Cancer Research (FNLCR), Frederick, MD 
      21702, USA.
FAU - Collins, Jack R
AU  - Collins JR
FAU - Singh, Nagendra
AU  - Singh N
FAU - W Wainer, Irving
AU  - W Wainer I
LA  - eng
GR  - HHSN261200800001C/RC/CCR NIH HHS/United States
GR  - HHSN261200800001E/CA/NCI NIH HHS/United States
GR  - ZIA AG000295-10/ImNIH/Intramural NIH HHS/United States
GR  - 261200800001E/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20120810
PL  - Netherlands
TA  - J Chromatogr A
JT  - Journal of chromatography. A
JID - 9318488
RN  - 61036-62-2 (Teicoplanin)
RN  - 89139-42-4 (teicoplanin aglycone)
RN  - UM20QQM95Y (Ifosfamide)
SB  - IM
MH  - Chromatography, Liquid/instrumentation/*methods
MH  - Ifosfamide/*isolation & purification/metabolism
MH  - *Models, Molecular
MH  - Molecular Docking Simulation
MH  - Stereoisomerism
MH  - Teicoplanin/*analogs & derivatives/chemistry
PMC - PMC3513553
MID - NIHMS401212
EDAT- 2012/08/25 06:00
MHDA- 2013/03/12 06:00
PMCR- 2013/12/21
CRDT- 2012/08/25 06:00
PHST- 2012/06/22 00:00 [received]
PHST- 2012/08/03 00:00 [revised]
PHST- 2012/08/06 00:00 [accepted]
PHST- 2012/08/25 06:00 [entrez]
PHST- 2012/08/25 06:00 [pubmed]
PHST- 2013/03/12 06:00 [medline]
PHST- 2013/12/21 00:00 [pmc-release]
AID - S0021-9673(12)01221-6 [pii]
AID - 10.1016/j.chroma.2012.08.019 [doi]
PST - ppublish
SO  - J Chromatogr A. 2012 Dec 21;1269:218-25. doi: 10.1016/j.chroma.2012.08.019. Epub 
      2012 Aug 10.