The enthalpy of formation of methionine revisited María Victoria Roux a , Rafael Notario a *, Marta Segura b , James S. Chickos c and Joel F. Liebman d Methionine (2-amino-4-(methylthio)butanoic acid) is a sulfur-containing essential a-amino acid. Despite its impor- tance, its enthalpy of formation is contentious. From the analysis of its polymorphism confirms that the previously reported calorimetric experiments were made in the temperature interval in which a phase transitions occurs. A new value for the enthalpy of formation is suggested based on these results, as well as G4 quantum chemical calculations and thermochemical estimates. From the analysis of experimental enthalpy of formation measurements, the group increment temperature adjusted enthalpy of sublimation, quantum chemical calculations, and difference quantity de- rived estimates, our recommended value for the gas phase enthalpy of formation of methionine is –(430  10) kJmol 1 . Copyright © 2012 John Wiley & Sons, Ltd. Supporting information may be found in the online version of this paper. Keywords: DSC; enthalpy of formation; G3 and G4 quantum chemical calculations; methionine; phase transitions; thermochemistry INTRODUCTION L-Methionine (2-amino-4-(methylthio)butanoic acid) (see Scheme 1) is a sulfur-containing essential a-amino acid and composes 2.4 mol-percent of average proteins. [1] It is an intermediate in the biosynthesis of a series of nonessential amino acids such as cysteine, cystine, carnitine and taurine from its derivative S-adenosyl methio- nine (SAM, SAMe, SAM-e). This compound is a common co-substrate involved in methyl group transfers. [2] Crystalline L-methionine presents polymorphism. In 1964, Hutchens et al. [3] measured by calorimetry the heat capacities of a pure sample of crystalline dry L-methionine in the temperature interval between T = 11 K and T = 350 K. The heat capacity curve of L-methionine as a function of temperature shows a peak in the temperature interval between 200 and 350 K with a maximum at T = 305.5 K. The calculated enthalpy of this transition was determined as Δ trans H= 5.44 kJ mol -1 . As results of the ATD study [4] reported by Sabbah and Minadakis, three phase transitions were observed in a dried commercial sample (Fluka) with a degree of purity greater than 99%. The intervals of temperature and enthalpies for the observed transitions were: 258 to 361 K (2.7 kJmol -1 ), 391 to 403 K (0.2 kJmol -1 ) and 408 to 430 K (0.1 kJmol -1 ). Despite the importance of this amino acid, reliable experimen- tal data of its enthalpy of formation is not available. The NIST Chemistry Webbook (NIST Standard Reference Database Number 69), [5] reports two experimental enthalpies of combustion, Δ c H o m (cr), of L-methionine at T = 298.15 K, –(3176.5  0.8) kJmol -1 determined by Tsuzuki et al. [6] using a static bomb combustion calorimeter, and –(3564.1  0.6) kJmol -1 reported by Sabbah and Minadakis, [4] using a rotatory bomb calorimeter. From the value reported by Sabbah and Minadakis, the calculated enthalpy of formation in the crystalline state, Δ f H o m cr ð Þ , at T = 298.15 K is – (577.5  0.7) kJmol -1 . In 1999, new values for the standard enthalpy of combustion and formation in the condensed state of L-methionine at T = 298.15 K, –(3248.4  3.0) kJmol -1 , and – (588.4  3.0) kJmol -1 , respectively, were reported by Yang et al . [7] For the enthalpies of sublimation, the NIST Chemistry Web- book [5] reports the value measured by Svec and Clyde, [8,9] Δ g cr H o m = (125.1  0.8) kJmol -1 at T = 455 K, determined from va- por pressure measurements in the temperature interval from 463 to 498 K. Sabbah and Minadakis have reported that this sub- stance at atmospheric pressure decomposes at a temperature around 430 K , rendering the sublimation enthalpy measured by Svec and Clyde somewhat suspect. We additionally note that the thermal decomposition process of methionine is compli- cated, i.e. produces numerous species, and so even at the “low” temperatures of Sabbah and Minadakis’ experiments, these results may also be problematic. [10–12] Sabbah and Minadakis [4] report three values for the enthalpy of sublimation in the temperature interval from 417 to 425 K. A mean value of 140.5 kJmol -1 at T = 421 K is calculated. Adjustment * Correspondence to: Rafael Notario, Institute of Physical Chemistry “Rocasolano”, CSIC, Serrano 119, 28006 Madrid, Spain. E-mail: rnotario@iqfr.csic.es a M. V. Roux, R. Notario Institute of Physical Chemistry “Rocasolano”, CSIC, Serrano 119, 28006 Madrid, Spain b M. Segura Perkin Elmer España S.L., Ronda de Poniente 19, 28760 Tres Cantos, Madrid, Spain c J. S. Chickos Department of Chemistry and Biochemistry, University of Missouri-St. Louis, One University Boulevard, St. Louis, Missouri 63121-4499, USA d J. F. Liebman Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, MD 21250, USA Research Article Received: 16 February 2012, Revised: 12 April 2012, Accepted: 16 April 2012, Published online in Wiley Online Library: (wileyonlinelibrary.com) DOI: 10.1002/poc.2961 J. Phys. Org. Chem. (2012) Copyright © 2012 John Wiley & Sons, Ltd.