Associations of the bacterial mutagenicity of halogenated 2(5H)-furanones with their MNDO-PM3 computed properties and mode of reactivity with sodium borohydride

Abstract

Electrophilicity as a general basis for both the mutagenicity and nucleophile inactivation of halogen-substituted 2(5H)-furanones was tested. Lowest unoccupied molecular orbital (LUMO) energy levels and stabilities of 2(5H)-furanone radical anions and C-2, C-3, and C-4 anionic hydride adducts were computed with MNDO-PM3 for each of 10 compounds. These three computed sets of values were considered electrophilicity indicators. Each individual value from a given indicator set was plotted against the logarithm of the Salmonella typhimurium (TA100) mutagenicities (log Mm) for each of the corresponding compounds. Highest occupied molecular orbital (HOMO) energy levels for the 10 compounds were also computed. Strong negative correlations were obtained from the plots of LUMO and radical anion stability against log Mm of the 10 compounds. Also, a negative correlation was observed for the plot of the stability of the C-4 anionic hydride adduct for a smaller set of six compounds possessing a 4-(chloromethyl)-2(5H)-furanone structure and having the same HOMO characteristics. HOMO energies failed to correlate with mutagenicity. Neither computed atomic charge nor 13C chemical shift values for the larger compound group of 10 correlated well with mutagenicity or with each other. Sodium borohydride and borodeuteride reductions of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone demonstrated experimentally that hydride became attached to C-4.

Untitled

“…It has been shown that MX decreases the dc electrical conductivity of collagen in the solid state and makes more difficult water liberation [10]. These results can be explained by the electrophilic properties of MX [11,12]. Probably either takes place the reduction of the number of specific sites at which water molecules can be bound to collagen, or stronger interactions in collagen-water-MX system are created.…”

A study of inactivation reactions of N-acetylcysteine with mucochloric acid, a mutagenic product of the chlorination of humic substances in water

“…Computed indicators of 2(5H)-furanone electrophilicity pointed to a difference Abbreviations: CI, chemical ionization; CIMS, chemical ionization mass spectrometry; COLOC, correlation spectroscopy via long-range couplings; COSY, 'H,'H-correlated 2D NMR spectroscopy; DMSO, dimethyl sulfoxide; EIMS, electron impact masa spectrometry; FAB-HRMS, fast atom bombardment-high-resolution mass spectrometry; GC-MS, tandem gas chromatography mass spectrometry; HPLC, high-pressure liquid chromatography; IR, infrared spectroscopy; MCA, 3,4-dichloro-5-hydroxy-2(5H)-furanone; MX, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone; NAC, N-acetylcysteine; NMR, nuclear magnetic resonance spectroscopy; NOE, nuclear Overhouser environment NMR spectroscopy; R,, retention factor; RMCA (reduced mucochloric acid), 3,4-dichloro-2(5H)-furanone; revipg, revertants per microgram; revirmol, revertants per micromole; RMX (reduced MX), 3-chloro-4-(dichloromethyl)-2(5H)-furanone; revinmol, revertants per nanomole; TA(100), Salmonella typhimurium tester strain TA100; TLC, thin-layer chromatography. in MCA and MX reactivity with a given nucleophile (19).…”

Computational Study of the Alkylation Reaction of the Nitrogen Mustard Mechlorethamine Using NBO Model and the QTAIM Theory

“…With this objective, one of the ways to theoretically quantify the interaction intensity between the nitrogen mustards and the guanine, besides the analysis of the highest occupied molecular orbital (HOMO) [12], lowest unoccupied molecular orbital (LUMO) [13] and its difference [14][15][16], it is through the NBO model [17]. A distinguishing feature of localized NBO functions is the simultaneous requirement of orthonormality and maximum occupancy, leading to compact expressions for atomic and bond properties [18].…”