Quantum mechanical quantitative structure-activity relationships to avoid mutagenicity.
OBJECTIVE
The purpose of this work is to develop a quantum mechanically based quantitative structure-activity relationship (QMQSAR or QSAR hereafter) adequate to predict and explain Ames TA100-derived mutagenicities for a number of organic molecules.


METHODS
A set of 35 structurally similar molecules with epoxide (oxirane) functionalities and systematic, reliable experimental data were selected to construct a QSAR model. The SAM1 quantum mechanical method was used to perform conformational analysis and properties calculations. This QM information was used to compute a variety of descriptors. From this a two-descriptor regression model was constructed.


RESULTS
The two descriptors are ESP-HACA-1/TMSA and HOMO-LUMO energy gap. Statistical results for the model: R(2)=0.857, R(adj)(2)=0.818,R(cv)(2)=0.848,s(2)=0.0618. The variance inflation factor and significance for both descriptors were 1.082 and <0.001, respectively. The descriptors are related to transport across a membrane and to reactivity.


CONCLUSIONS
The model we have presented here facilitates design of non-mutagenic monomers that may be useful for dental restorative composites. The model also serves as a screening tool for rating the mutagenicity of new candidate materials.
Holder
Andrew J
AJ
Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110, United States. holdera@umkc.edu
Ye
Lin
L
D002244:Carbon / Q000737:chemistry; D003188:Composite Resins / Q000737:chemistry; D003764:Dental Materials / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry*; D005027:Ethylene Oxide / Q000737:chemistry; D005544:Forecasting; D006219:Halogens / Q000737:chemistry; D006801:Humans; D006878:Hydroxides / Q000737:chemistry; D008422:Materials Testing; D008956:Models, Chemical; D008968:Molecular Conformation; D009153:Mutagens / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D012044:Regression Analysis
D003188:Composite Resins; D003764:Dental Materials; D004852:Epoxy Compounds; D006219:Halogens; D006878:Hydroxides; D009153:Mutagens; D002244:Carbon; C031356:hydroxide ion; D005027:Ethylene Oxide