Abstract:The decarboxylation of
N-carboxy-2-imidazolidinone has previously been established
as a model for the
transfer of carbon dioxide from N(1‘)-carboxybiotin.
The present paper reports the pH-dependence of the
reaction
as well as the acceleration of the reaction in methanol and in
acetonitrile. These results suggest that enzymic
reactions
of N(1‘)-carboxybiotin in a hydrophobic active site with
decreased hydrogen bonding can be rapid if the energy of
desolvation is compensated by the energy made available by assoc… Show more
“…In a previous paper, we reported the results for the decarboxylation reaction of the model compound N -carboxy-2-imidazolidinone anion in aqueous solution from a combined quantum mechanics and molecular mechanics (QM/MM) Monte Carlo simulation study. Our calculated free energy of activation, 22.7 ± 0.2 kcal/mol, is in excellent agreement with the experimental value of 23.2 kcal/mol obtained by Rahil et al for the same model reaction . Through these studies, insights on the energetics and factors that govern the dramatic solvent effects on the anionic process in aqueous solution have been obtained.…”
Section: Introductionsupporting
confidence: 90%
“…The decarboxylation of N -carboxy-2-imidazolidinone ( 1 ) in solution proceeds via two mechanisms, depending on the pH of the solution (Scheme ). − Experimentally, at pH > 8, the rate of the reaction is independent of the pH, consistent with a loss of carbon dioxide from the ionized carboxylate form (eq 2), which was modeled previously . Below pH 8, the observed rate increases with increased acidity, until a plateau is reached at pH 4, suggesting a reaction via a neutral transition state . The acidity constant of 1 was determined to be p K a = 4.2 by Rahil et al 1 …”
The solvent effects on the decarboxylation reaction of neutral N-carboxy-2-imidazolidinone in aqueous solution have been investigated by a combined quantum mechanical and molecular mechanical (QM/MM) Monte Carlo simulation method. In the present approach, the gas-phase intrinsic reaction coordinate of the reaction was first obtained by ab initio molecular orbital calculations at the RHF/6-31+G(d) level. Then, the potential of mean force for the decarboxylation reaction was determined via statistical perturbation theory using the combined QM/MM-AM1/ TIP3P potential in Monte Carlo simulations. A two-stage mechanism consisting of the intramolecular proton transfer and N-C bond cleavage with the N-C bond breaking as the rate-limiting step was found. The computed free energy of activation in water is 21.0 ( 0.2 kcal/mol, in good agreement with the experimental value of 20.7 kcal/mol. Analyses of the structural and energetic nature of the differential solvation along the reaction coordinate are presented.
“…In a previous paper, we reported the results for the decarboxylation reaction of the model compound N -carboxy-2-imidazolidinone anion in aqueous solution from a combined quantum mechanics and molecular mechanics (QM/MM) Monte Carlo simulation study. Our calculated free energy of activation, 22.7 ± 0.2 kcal/mol, is in excellent agreement with the experimental value of 23.2 kcal/mol obtained by Rahil et al for the same model reaction . Through these studies, insights on the energetics and factors that govern the dramatic solvent effects on the anionic process in aqueous solution have been obtained.…”
Section: Introductionsupporting
confidence: 90%
“…The decarboxylation of N -carboxy-2-imidazolidinone ( 1 ) in solution proceeds via two mechanisms, depending on the pH of the solution (Scheme ). − Experimentally, at pH > 8, the rate of the reaction is independent of the pH, consistent with a loss of carbon dioxide from the ionized carboxylate form (eq 2), which was modeled previously . Below pH 8, the observed rate increases with increased acidity, until a plateau is reached at pH 4, suggesting a reaction via a neutral transition state . The acidity constant of 1 was determined to be p K a = 4.2 by Rahil et al 1 …”
The solvent effects on the decarboxylation reaction of neutral N-carboxy-2-imidazolidinone in aqueous solution have been investigated by a combined quantum mechanical and molecular mechanical (QM/MM) Monte Carlo simulation method. In the present approach, the gas-phase intrinsic reaction coordinate of the reaction was first obtained by ab initio molecular orbital calculations at the RHF/6-31+G(d) level. Then, the potential of mean force for the decarboxylation reaction was determined via statistical perturbation theory using the combined QM/MM-AM1/ TIP3P potential in Monte Carlo simulations. A two-stage mechanism consisting of the intramolecular proton transfer and N-C bond cleavage with the N-C bond breaking as the rate-limiting step was found. The computed free energy of activation in water is 21.0 ( 0.2 kcal/mol, in good agreement with the experimental value of 20.7 kcal/mol. Analyses of the structural and energetic nature of the differential solvation along the reaction coordinate are presented.
“…N -carboxy-2-imidazolidone is formed by the alkaline hydrolysis of N -carboxymethoxy-2-imidazolidone, and once formed, it decarboxylates spontaneously to give CO 2 and 2-imidazolidone. The rate of decarboxylation is very pH-dependent, with N -carboxy-2-imidazolidone being more stable at high pH and rapidly decarboxylating at neutral and low pH. , By use of an excess of alkali, the N -carboxy-2-imidazolidone can be formed fairly rapidly, and at pH 14 the carbamate ester carbonyl stretch of the parent compound disappears in approximately 10 min, indicating that hydrolysis of the ester is complete.…”
Section: Resultsmentioning
confidence: 99%
“…Indeed, Caplow, in his pioneering study, used an infrared assay, in the 1600−1700 cm -1 region, to study the decarboxylation kinetics of the imidazolidone complex between pH 7 and 10 . In Figure , the Raman peak at 936 cm -1 is due to the symmetric ring breathing mode of 2-imidazolidone, which is formed in small amounts by C−N cleavage in a side reaction while the ester is being hydrolyzed . Methanol is the also produced upon carbamate ester hydrolysis, and the C−O stretch of methanol is observed at 1018 cm -1 .…”
The spontaneous decarboxylation of N-carboxy-2-imidazolidone (a model for carboxybiotin) and N(1‘)-carboxybiotin can be followed at high pH by Raman and FTIR spectroscopies. The major bands associated
with vibrations of the carboxylate group have been assigned on the basis of quantum mechanical calculations
of N-carboxy-2-imidazolidone and N(1‘)-carboxy-2-methylbiotin. The carboxylate modes are the asymmetric
stretch, coupled to the ureido carbonyl stretch, near 1710 cm-1, the symmetric stretch near 1340 cm-1, and
the −CO2
- scissoring motion near 830 cm-1. In the case of carboxybiotin, the last two modes are strongly
coupled with biotin ring modes. All three carboxylate modes disappear as spontaneous decarboxylation occurs,
to be replaced by features attributable to the noncarboxylated ring structures.The HF/6-31G* optimized structure
of 2-methylbiotin revealed that the ureido ring portion is essentially planar, in accord with a number of X-ray
crystallographic structures of biotin compounds. However, calculations at this level and at the B3LYP/6-31+G(d) level (using density functional theory) predict that the ureido ring in biotin puckers upon carboxylation.
Comparison of the structures of carboxybiotin and carboxyimidazolidone, derived at the HF/6-31G* level,
indicates that lengths of the ring-nitrogen-to-carboxylate bonds are equal and that the torsional angles about
this linkage are very similar. This strong structural similarity provides a rationale for the observation that, at
high pH, the spontaneous rates of decarboxylation of these two molecules are very similar.
“…Table summarizes the computed activation free energies for the decarboxylation processes relative to the carboxylate anions, free energies of reaction, and hydration free energies for all of these reactions from the PMFs, and Figure depicts the correlation between the computed and experimental free energy barriers. ,,− Overall, the dual-level estimates of the free energy barriers are in accord with the experimental values, with a correlation coefficient of 0.883, spanning a range of 29 orders of magnitude in reaction rate or a difference of about 39 kcal/mol in barrier height. An exception is trifluoroacetate ion, whose free energy barrier from the experimental rate constant is 34.2 kcal/mol , whereas the dual-level simulations yielded a free energy of activation of 25.1 kcal/mol.…”
Carbon dioxide capture,
corresponding to the recombination process
of decarboxylation reactions of organic acids, is typically barrierless
in the gas phase and has a relatively low barrier in aprotic solvents.
However, these processes often encounter significant solvent-reorganization-induced
barriers in aqueous solution if the decarboxylation product is not
immediately protonated. Both the intrinsic stereoelectronic effects
and solute–solvent interactions play critical roles in determining
the overall decarboxylation equilibrium and free energy barrier. An
understanding of the interplay of these factors is important for designing
novel materials applied to greenhouse gas capture and storage as well
as for unraveling the catalytic mechanisms of a range of carboxy lyases
in biological CO
2
production. A range of decarboxylation
reactions of organic acids with rates spanning nearly 30 orders of
magnitude have been examined through dual-level combined quantum mechanical
and molecular mechanical simulations to help elucidate the origin
of solvation-induced free energy barriers for decarboxylation and
the reverse carboxylation reactions in water.
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