PMID- 23036090
OWN - NLM
STAT- MEDLINE
DCOM- 20130501
LR  - 20121126
IS  - 1549-960X (Electronic)
IS  - 1549-9596 (Linking)
VI  - 52
IP  - 11
DP  - 2012 Nov 26
TI  - Combinatorial x computational x cheminformatics (C3) approach to characterization 
      of congeneric libraries of organic pollutants.
PG  - 2902-9
LID - 10.1021/ci300289b [doi]
AB  - Congeners are molecules based on the same carbon skeleton but are different by 
      the number of substituents and/or a substitution pattern. Examples are 
      1-chloronaphthalene, 1,4-dichloronaphthalene, and 1,3,8-trichloronaphthalene. 
      Various persistent organic pollutants (POPs) exist in the environment as families 
      of congeners. Very large numbers of possible congeners make their experimental 
      characterization and risk assessment unfeasible. Computational high-throughput 
      and quantitative structure-property relationship (QSPR) modeling has been limited 
      by the lack of tools and approaches facilitating analysis of such POP families. 
      We present a comprehensive approach that enables modeling of extremely large 
      congeneric libraries. The approach involves three steps: (1) combinatorial 
      generation of a library of congeners, (2) quantum chemical characterization of 
      each structure at the PM6 semiempirical level to obtain molecular descriptors, 
      and (3) analysis of the information generated in step 2. In steps 1-3, we employ 
      combinatorial, computational, and cheminformatics techniques, respectively. 
      Therefore, this hybrid approach is named "Combinatorial x Computational x 
      Cheminformatics", or just abbreviated as C(3) (or C-cubed) approach. We 
      demonstrate the usefulness of this approach by generating and characterizing Br- 
      and Cl-substituted congeneric families of 23 typical POPs. The analysis of the 
      resulting set of 1 840 951 congeners that includes Cl-, Br-, and mixed 
      Br/Cl-substituted species, proves that, based on structural similarities defined 
      by the molecular descriptors' values, the existing QSPR models developed 
      originally for Cl- and Br-substituted congeners can be applied also to mixed 
      Br/Cl-substituted ones. Thus, the C(3) approach may serve as a tool for exploring 
      structural applicability domains of the existing QSPR models for congeneric sets.
FAU - Haranczyk, Maciej
AU  - Haranczyk M
AD  - Computational Research Division, Lawrence Berkeley National Laboratory, One 
      Cyclotron Road, Mail Stop 50F-1650, Berkeley, California 94720-8139, USA. 
      mharanczyk@lbl.gov
FAU - Urbaszek, Piotr
AU  - Urbaszek P
FAU - Ng, Esmond G
AU  - Ng EG
FAU - Puzyn, Tomasz
AU  - Puzyn T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20121023
PL  - United States
TA  - J Chem Inf Model
JT  - Journal of chemical information and modeling
JID - 101230060
RN  - 0 (Environmental Pollutants)
RN  - 0 (Hydrocarbons, Brominated)
RN  - 0 (Hydrocarbons, Chlorinated)
RN  - 0 (Small Molecule Libraries)
SB  - IM
MH  - Environmental Monitoring
MH  - Environmental Pollutants/*chemistry/classification
MH  - Humans
MH  - Hydrocarbons, Brominated/*chemistry/classification
MH  - Hydrocarbons, Chlorinated/*chemistry/classification
MH  - Models, Chemical
MH  - Quantitative Structure-Activity Relationship
MH  - Quantum Theory
MH  - *Small Molecule Libraries
EDAT- 2012/10/06 06:00
MHDA- 2013/05/02 06:00
CRDT- 2012/10/06 06:00
PHST- 2012/10/06 06:00 [entrez]
PHST- 2012/10/06 06:00 [pubmed]
PHST- 2013/05/02 06:00 [medline]
AID - 10.1021/ci300289b [doi]
PST - ppublish
SO  - J Chem Inf Model. 2012 Nov 26;52(11):2902-9. doi: 10.1021/ci300289b. Epub 2012 
      Oct 23.