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Reaction Kinetics And Biological Action In Barley Of Mono-functional Methanesulfonic Esters.

S. Osterman-Golkar, L. Ehrenberg, C. A. Wachtmeister
Published 1970 · Biology

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Abstract 1. As a background for studies of the action mechanisms of biological alkylating agents a number of methanesulfonic esters were investigated with respect to rates of hydrolysis and reaction with different nucleophiles, mostly at 20°, 25° and 37°. 2. The reaction patterns of monofunctional alkylating agents (AA) of the kind studied were characterized in terms of (a) reaction mechanism (S N 1 or S N 2); (b) the S wain -S cott (61,64) substrate constant s describing the dependence of bimolecular rate constant on nucleophilicity n of the receptor molecule; (c) the absolute reaction rates and their temperature dependence which are accurately described by activation energy E A (≈ activation enthalpy, Δ H *) and activation entropy Δ S *, the latter parameter giving, in addition, information about the reaction mechanism. 3. In the series of unsubstituted alkyl esters studied, which mostly react according to S N 2, branching on the α-carbon, as in iPMS, gives predominantly S N 1 type reaction. The strong steric hindrance of S N 2 reaction provoked by β-branching, as in iBMS and NeoMS, leads to the appearance of an S N 1 type behaviour at low n , e.g. in hydrolysis. Of substituents studied, β-hydroxy and β-methoxy decrease reactivity, without considerable influence on s . β-Positioned carbonyl gives very high values of s (i.e. gives a character of “SH inhibitors”) to the compounds, with a strong retardation of reaction rate at low n . In certain cases abnormally high rates of reaction with the hydroxyl ion are encountered. Thus β-OH (as in HOEMS) leads to 1,2-epoxide formation in rapid OH − catalyzed reaction; β-carbonyl compounds exhibit a strongly OH − dependent hydrolysis. 4. In barley kernels the toxic action of the AA is in most instances reconcilable with alkylation at n ≈ 5·1, which corresponds to cysteine ester at pH 7, whereas genetic effects apparently are caused by alkylation of centres with n = 2·5–3, corresponding to primary phosphate and DNA. Kernels are therefore presumably killed by protein alkylation, e.g. leading to enzyme inactivation, whereas mutation (including sterility) is probably induced by DNA alkylation. Exceptions are the α-branched esters, indicated to kill by genetic mechanisms, and β-branched esters which are also more toxic than expected from kinetic data, however, for unknown reasons. iPMS (low s ) induces mutation in a linear function of dose, whereas EMS and other esters of medium s exhibit an exponential dose response curve, possibly through simultaneous alkylation of DNA and protein, e.g. impairing repair enzyme function. The slight sterility induced by β-carbonyl esters implies that protein alkylation alone may provoke a certain genetic damage. 5. Experiments imply that, for a deeper understanding of the biological action of AA, the following factors should also be considered: (a) secondary reactions after alkylation of, e.g. DNA (especially important for chromosomal aberrations) and protein; (b) lipid/water partition; (c) steric factors on the side of AA as well as the receptor molecule.
This paper references
10.1021/JA01097A041
Quantitative Correlation of Relative Rates. Comparison of Hydroxide Ion with Other Nucleophilic Reagents toward Alkyl Halides, Esters, Epoxides and Acyl Halides1
C. G. Swain (1953)
10.1039/JR9640003513
678. Nucleophilic reactivity. Part V. The reaction between amines and ethyl methanesulphonate
R. F. Hudson (1964)
Induced mutation in plants: mechanisms and principles.
L. Ehrenberg (1960)
10.3891/ACTA.CHEM.SCAND.22-2727
Effects of beta-hydroxyethylation and beta-methoxyethylation on DNA in vitro.
S. Walles (1968)
10.1016/0003-9861(62)90047-4
Physicochemical changes produced in DNA after alkylation.
J. Lett (1962)
10.1016/0014-4827(66)90273-4
Effects of diethyl pyrocarbonate on barley seeds.
A. T. Natarajan (1966)
10.1021/JA01640A037
Organic Peroxides. II. Secondary Alkyl Hydroperoxides
H. Williams (1954)
10.1017/S0016672300003736
The induction of dominant lethal mutations in rats by alkane sulphonic esters
M. Partington (1963)
10.1111/J.1601-5223.1967.TB02144.X
Studies on the uptake of ethyl methanesulfonate into embryos of barley.
S. Walles (1967)
10.3891/ACTA.CHEM.SCAND.21-0831
Influence of Monofunctional Alkylation on the Reversibility of Heat Denaturation of DNA. Preliminary Report.
S. Walles (1967)
10.1146/ANNUREV.PC.11.100160.000433
Physical organic chemistry
J. Hine (1960)
10.1021/JA01377A012
KINETIC STUDIES ON ETHYLENE OXIDES
J. N. Brönsted (1929)
10.3891/ACTA.CHEM.SCAND.22-2043
Synthesis of Mesyloxyacetic Acid and some Derivatives.
Olavi Havbrandt (1968)
10.1021/JA01140A040
Mechanism of the Reaction of α-Haloketones with Weakley Basic Nucleophilic Reagents
R. Pearson (1952)
10.1039/JR9580001356
273. The reactivity of esters of quinquevalent phosphorus towards anions
R. Hudson (1958)
10.1042/BJ0890127
FURTHER STUDIES ON THE ALKYLATION OF NUCLEIC ACIDS AND THEIR CONSTITUENT NUCLEOTIDES.
P. D. Lawley (1963)
10.3891/ACTA.CHEM.SCAND.22-0711
Synthesis of 2-Hydroxyethyl Methanesulfonate.
S. Osterman-Golkar (1968)
10.1016/S0033-7560(66)80098-4
Nachwäsche, rücktrocknung und lagerung bei äms-behandelten gerstensamen
K. Bender (1966)
10.1038/164938A0
New evidence on the mode of action of ‘mitotic poisons’
A. Loveless (1949)
10.1021/JA01518A020
Sulfur-Oxygen Scission versus Carbon-Oxygen Scission in Reactions of 2,4-Dinitrophenyl p-Toluenesulfonate and Related Esters with Nucleophilic Reagents1
J. Bunnett (1959)
10.1038/210762A0
Chromosome Breakage with Two Isomers of l-Threitol 1,4-bismethanesulphonate in Plants
J. Moutschen (1966)
10.1039/TF9484400045
The replacement reactions of β-β′-dichlorodiethyl sulphide and of some analogues in aqueous solution: the isolation of β-chloro-β′-hydroxy diethyl sulphide
A. Ogston (1948)
10.1139/V56-099
THE PREPARATION AND SOME CLEAVAGE REACTIONS OF ALKYL AND SUBSTITUTED ALKYL METHANESULPHONATES: THE SYNTHESIS OF FLUORIDES, IODIDES, AND THIOCYANATES
F. L. Pattison (1956)
10.1139/V52-025
THE CHEMISTRY OF ETHYLENE OXIDE: V. THE REACTION OF ETHYLENE OXIDE WITH HALIDE IONS IN NEUTRAL AND ACID SOLUTION
A. M. Eastham (1952)
10.1016/0027-5107(65)90043-6
Mutagenicity of some alkyl alkanesulfonates in barley.
R. Rao (1965)
10.3891/ACTA.CHEM.SCAND.20-0107
Effects of diethyl pyrocarbonate and methyl methanesulfonate on nucleic acids and nucleases.
I. Fedorcsák (1966)
10.1021/JA01477A030
The Behavior of the t-Pentyl Cation as Produced in Deaminations and Halide Solvoyses1
M. S. Silver (1961)
10.1139/V61-108
THE HYDROLYSIS OF A SERIES OF STRAIGHT-CHAIN ALKYL METHANESULPHONIC ESTERS IN WATER
P. Barnard (1961)
10.1016/0027-5107(67)90112-1
Induction of chromosome aberrations in cultured human cells by ethylenimine and its relation to cell cycle.
T. Chang (1967)
10.1038/1661113a0
Chromosome Alteration and Tumour Inhibition by Nitrogen Mustards: the Hypothesis of Cross-linking Alkylation
A. Loveless (1950)
10.1016/S0033-7560(70)80059-X
Influence of pH and temperature on the effects of ethylenimine (EI) in wheat and barley seeds
K. Konstantinov (1970)
10.1039/QR9571100001
Quantitative study of steric hindrance
C. K. Ingold (1957)
10.1016/0027-5107(69)90002-5
Reaction rates and biological action of alkylating agents. Preliminary report on bactericidal and mutagenic action in E. coli.
I. Turtóczky (1969)
10.1038/163667A0
Mode of Production of Chromosome Abnormalities by the Nitrogen Mustards The Possible Role of Cross-Linking
R. Goldacre (1949)
10.1139/V60-276
NUCLEOPHILIC DISPLACEMENT OF METHYL SULPHONIC ESTERS BY HYDROXIDE ION IN WATER
S. Hartman (1960)
10.1021/JA01075A025
The Effect of the Carbonyl and Related Groups on the Reactivity of Halides in SN2 Reactions
F. Bordwell (1964)
10.3891/ACTA.CHEM.SCAND.23-1080
Determination of the rate constants for alkylation of DNA in vitro with methanesulfonic esters.
S. Walles (1969)
10.1016/S0065-3233(08)60029-7
The proteins of the exocrine pancreas.
P. Desnuelle (1961)
10.1139/V57-175
SOLVOLYSIS IN HYDROGEN AND DEUTERIUM OXIDE: II. STRONGLY SOLVATED SUBSTRATES
R. Robertson (1957)
10.1042/BJ0800496
The reaction of mono- and di-functional alkylating agents with nucleic acids.
P. Brookes (1961)
10.1021/JA01125A002
Neighboring Carbon and Hydrogen. VI. Formolysis and Other Solvolysis Rates of Some Simple Secondary and Primary Benzenesulfonates1
S. Winstein (1952)
10.1080/00015125409439952
Ion Density and Biological Effectiveness of Radiations
L. Ehrenberg (1954)
10.1111/J.1601-5223.1968.TB02208.X
Note on the chromosome breaking activity of ethylene oxide and ethyleneimine.
J. Moutschen-Dahmen (1968)
10.1016/S0033-7560(65)80124-7
Localisation intracellulaire du methane sulfonate d'ethyl (EMS) tritie chez
M. Moutschen-Dahmen (1965)
Chemical mutagenesis: biochemical and chemical points of view on mechanisms of action.
L. Ehrenberg (1960)
10.1016/0027-5107(70)90113-2
Reaction rates and biological action of N-methyl- and N-ethyl-N-nitrosourea.
J. Velemínský (1970)
10.1021/JA01546A062
Reactions of Ethylenimines. IX. The Mechanisms of Ring Openings of Ethylenimines in Acidic Aqueous Solutions1
J. Earley (1958)
10.1021/JA01154A545
DISPLACEMENT REACTIONS IN NEOPENTYL-TYPE SYSTEMS1
F. Bordwell (1951)



This paper is referenced by
10.1016/0165-1110(84)90007-1
A review of the genetic effects of ethyl methanesulfonate.
G. Sega (1984)
10.1016/0165-1110(92)90025-5
DNA adduct formation by 12 chemicals with populations potentially suitable for molecular epidemiological studies.
M. Uziel (1992)
10.1002/JCC.540100413
An MNDO molecular orbital study of the reactions of protonated oxirane derivatives (XCHCH2OH+, X = CN, Cl, CH3, Ph) with simple nucleophiles. Implications for regioselectivity in the reactions of electrophiles with nucleic acid bases
G. Ford (1989)
10.1007/978-1-4899-2052-2_1
Introduction to “Molecular Dosimetry”
L. Ehrenberg (1993)
10.1016/J.MRGENTOX.2004.11.004
Reaction-kinetic parameters of glycidamide as determinants of mutagenic potency.
V. Silvari (2005)
10.1016/0027-5107(89)90143-7
Mutagenesis of ΦX174 am3 cs70 incorporated into the genome of mouse L-cells
J. Burkhart (1989)
10.1016/0027-5107(81)90023-3
Alkylating properties and genetic activity of 4-vinylcyclohexene metabolites and structurally related epoxides.
G. Turchi (1981)
10.1016/0027-5107(74)90102-X
Some chemical aspects of dose-response relationships in alkylation mutagenesis.
P. D. Lawley (1974)
10.1016/0165-1161(92)90029-L
Micronucleated reticulocyte induction by ethylating agents in mice.
A. Asita (1992)
10.1016/0027-5107(78)90098-2
Ethylation of DNA and protamine by ethyl methanesulfonate in the germ cells of male mice and the relevancy of these molecular targets to the induction of dominant lethals.
G. Sega (1978)
10.1002/TCM.1770010110
Carcinogen-DNA interaction: differential effects of distamycin-a and spermine on the formation of 7-methylguanine in DNA by N-methyl-N-nitrosourea, methylmethanesulfonate, and dimethylsulfate.
S. Rajalakshmi (1980)
10.1016/0165-1161(76)90079-0
Comparative effects of ionizing radiation and two gaseous chemical mutagens on somatic mutation induction in one mutable and two non-mutable clones of tradescantia
C. H. Nauman (1976)
10.1016/S0033-7560(74)80035-9
On the reaction kinetics and mutagenic activity of methylating and β-halogenoethylating gasoline additives
L. Ehrenberg (1974)
10.1016/0165-1110(80)90028-7
Genetic effects of dimethyl sulfate, diethyl sulfate, and related compounds.
G. Hoffmann (1980)
10.1016/0027-5107(95)00040-P
DNA damage and repair in somatic and germ cells in vivo.
E. Vogel (1995)
10.1016/0027-5107(71)90089-3
Recovery or increase of induced genetical effects dependent upon the moisture content of stored N-methyl-N-nitrosourea-treated barley seeds
T. Gichner (1971)
10.1016/0027-5107(69)90002-5
Reaction rates and biological action of alkylating agents. Preliminary report on bactericidal and mutagenic action in E. coli.
I. Turtóczky (1969)
10.1016/0027-5107(83)90066-0
Methylation of DNA and protamine by methyl methanesulfonate in the germ cells of male mice.
G. Sega (1983)
10.1016/j.cbi.2018.03.017
Reaction kinetic studies for comparison of mutagenic potency between butadiene monoxide and glycidamide.
Hitesh V. Motwani (2018)
10.1016/0027-5107(83)90140-9
Quantitative comparison of carcinogenicity, mutagenicity and electrophilicity of 10 direct-acting alkylating agents and of the initial O6:7-alkylguanine ratio in DNA with carcinogenic potency in rodents.
H. Bartsch (1983)
10.1016/0006-291X(77)90720-3
Alkylation of DNA and proteins in mice exposed to vinyl chloride.
S. Osterman-Golkar (1976)
10.1016/S0033-7560(70)80059-X
Influence of pH and temperature on the effects of ethylenimine (EI) in wheat and barley seeds
K. Konstantinov (1970)
10.1016/0027-5107(94)90123-6
International Commission for Protection Against Environmental Mutagens and Carcinogens. The subtlety of alkylating agents in reactions with biological macromolecules.
E. Vogel (1994)
10.1016/0027-5107(86)90112-0
The use of alkaline elution procedures to measure DNA damage in spermiogenic stages of mice exposed to methyl methanesulfonate.
G. Sega (1986)
10.1016/0165-7992(82)90153-1
Chromosomal aberrations induced by ethylene oxide in a human amniotic cell line in vitro.
V. Poirier (1982)
10.1007/978-1-4613-0637-5_31
Repair of O6-methylguanine damage in normal human tissues.
S. M. D'Ambrosio (1990)
10.1016/0027-5107(74)90170-5
Reaction kinetics of N-methyl-N'-nitro-N-nitrosoguanidine and N-ethyl-N'-nitro-N-nitrosoguanidine.
S. Osterman-Golkar (1974)
Molecular analysis of mutations induced in the vermilion gene of Drosophila melanogaster by methyl methanesulfonate.
M. Nivard (1992)
10.1016/0027-5107(91)90200-8
Developmental response of zygotes exposed to similar mutagens.
W. Generoso (1991)
10.3109/00498257209111060
The alkylating properties of organophosphates.
C. Bedford (1972)
10.1080/09553007514550321
Prophage inductive efficiency of alkylating agents and radiations.
S. Hussain (1975)
10.1016/0165-1161(76)90156-4
Molecular dosimetry of chemical mutagens. Measurement of molecular dose and DNA repair in mammalian germ cells.
G. Sega (1976)
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