In an effort to establish reliable thermodynamic data for amino acids, heat capacity and phase behavior are reported for L-cysteine (CAS RN: 52-90-4), L-serine (CAS RN: 56-45-1), L-threonine (CAS RN: 72-19-5), L-lysine (CAS RN: 56-87-1), and L-methionine (CAS RN: 63-68-3). Prior to heat capacity measurements, initial crystal structures were identified by X-ray powder diffraction, followed by a thorough investigation of the polymorphic behavior using differential scanning calorimetry in the temperature range from 183 K to the decomposition temperature determined by thermogravimetric analysis. Crystal heat capacities of all five amino acids were measured by Tian-Calvet calorimetry in the temperature interval (262-358) K and by power compensation DSC in the temperature interval from 215 K to over 420 K. Experimental values of this work were compared and combined with the literature data obtained with adiabatic calorimetry. Low-temperature heat capacities of L-threonine and L-lysine, for which no or limited literature data was available, were measured using the relaxation (heat pulse) calorimetry. As a result, reference heat capacities and thermodynamic functions for the crystalline phase from near 0 K to over 420 K were developed.

Central Laboratories University of Chemistry and Technology Prague Technická 5 CZ 166 28 Prague Czech Republic

Department of Physical Chemistry University of Chemistry and Technology Prague Technická 5 CZ 166 28 Prague Czech Republic

Institute of Macromolecular Chemistry Czech Academy of Sciences Heyrovského nám 2 CZ 162 06 Prague Czech Republic

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Pokorný V., Červinka C., Štejfa V., Havlín J., Růžička K., Fulem M. Heat Capacities of L-Alanine, L-Valine, L-Isoleucine, and L-Leucine: Experimental and Computational Study. J. Chem. Eng. Data. 2020;65:1833–1849.

Štejfa V., Pokorný V., Miranda C.F.P., Fernandes Ó.O.P., Santos L.M.N.B.F. Volatility Study of Amino Acids by Knudsen Effusion with QCM Mass Loss Detection. ChemPhysChem. 2020;21:938–951. PubMed

Pokorný V., Lieberzeitová E., Štejfa V., Havlín J., Fulem M., Růžička K. Heat Capacities of l-Arginine, l-Aspartic Acid, l-Glutamic Acid, l-Glutamine, and l-Asparagine. Int. J. Thermophys. 2021;42:160.

Pokorný V., Štejfa V., Havlín J., Růžička K., Fulem M. Heat Capacities of l-Histidine, l-Phenylalanine, l-Proline, l-Tryptophan and l-Tyrosine. Molecules. 2021;26:4298. doi: 10.3390/molecules26144298. PubMed DOI PMC

Štejfa V., Fulem M., Růžička K. Ideal-gas thermodynamic properties of proteinogenic aliphatic amino acids calculated by R1SM approach. J. Chem. Phys. 2019;151:144504. doi: 10.1063/1.5123450. PubMed DOI

Drauz K., Grayson I., Kleemann A., Krimmer H.-P., Leuchtenberger W., Weckbecker C. Ullmann′s Encyclopedia of Industrial Chemistry. Wiley-VCH Verlag GmbH & Co. KGaA; Weinheim, Germany: 2000. Amino Acids.

Metcalf J.S., Dunlop R.A., Powell J.T., Banack S.A., Cox P.A. L-Serine: A Naturally-Occurring Amino Acid with Therapeutic Potential. Neurotox. Res. 2018;33:213–221. doi: 10.1007/s12640-017-9814-x. PubMed DOI

Newman A., Reutzel-Edens S.M., Zografi G. Coamorphous Active Pharmaceutical Ingredient-Small Molecule Mixtures: Considerations in the Choice of Coformers for Enhancing Dissolution and Oral Bioavailability. J. Pharm. Sci. 2018;107:5–17. PubMed

Williams P.A., Hughes C.E., Martin J., Courvoisier E., Buanz A.B.M., Gaisford S., Harris K.D.M. Understanding the Solid-State Hydration Behavior of a Common Amino Acid: Identification, Structural Characterization, and Hydration/Dehydration Processes of New Hydrate Phases of l-Lysine. J. Phys. Chem. C. 2016;120:9385–9392.

Williams P.A., Hughes C.E., Harris K.D.M. L-Lysine: Exploiting Powder X-ray Diffraction to Complete the Set of Crystal Structures of the 20 Directly Encoded Proteinogenic Amino Acids. Angew. Chem. Int. Ed. 2015;54:3973–3977. doi: 10.1002/anie.201411520. PubMed DOI

Araki K., Ozeki T. Kirk-Othmer Encyclopedia of Chemical Technology. John Wiley & Sons, Inc.; Hoboken, NJ, USA: 2000. Amino Acids.

Lukyanova V.A., Druzhinina A.I., Pimenova S.M., Ioutsi V.A., Buyanovskaya A.G., Takazova R.U., Sagadeev E.V., Gimadeev A.A. Thermodynamic properties of l-threonine. J. Chem. Thermodyn. 2018;116:248–252. doi: 10.1016/j.jct.2017.09.022. DOI

Weiss I.M., Muth C., Drumm R., Kirchner H.O.K. Thermal decomposition of the amino acids glycine, cysteine, aspartic acid, asparagine, glutamic acid, glutamine, arginine and histidine. BMC Biophys. 2018;11:2. doi: 10.1186/s13628-018-0042-4. PubMed DOI PMC

Do H.T., Chua Y.Z., Kumar A., Pabsch D., Hallermann M., Zaitsau D., Schick C., Held C. Melting properties of amino acids and their solubility in water. RSC Advances. 2020;10:44205–44215. PubMed PMC

Rodante F., Marrosu G. Thermal analysis of some α-amino acids using simultaneous TG-DSC apparatus. The use of dynamic thermogravimetry to study the chemical kinetics of solid state decomposition. Thermochim. Acta. 1990;171:15–29.

Rodriguez-Mendez M.L., Rey F.J., Martin-Gil J., Martin-Gil F.J. DTG and DTA studies on amino acids. Thermochim. Acta. 1988;134:73–78. doi: 10.1016/0040-6031(88)85219-5. DOI

Pielichowski K., Flejtuch K. Differential scanning calorimetry studies on poly(ethylene glycol) with different molecular weights for thermal energy storage materials. Polym. Adv. Technol. 2002;13:690–696. doi: 10.1002/pat.276. DOI

Olafsson P.G., Bryan A.M. Evaluation of thermal decomposition temperatures of amino acids by differential enthalpic analysis. Microchim. Acta. 1970;58:871–878. doi: 10.1007/BF01225712. PubMed DOI

Wesolowski M., Erecińska J. Relation between chemical structure of amino acids and their thermal decomposition. J. Therm. Anal. Calorim. 2005;82:307–313. doi: 10.1007/s10973-005-0895-z. DOI

Rodante F., Fantauzzi F., Catalani G. Thermal analysis of a series of dipeptides having α-alanine as the first term. Mutual influence of structures. Thermochim. Acta. 1996;284:351–365.

Rodante F., Marrosu G., Catalani G. Thermal analysis of different series of dipeptides. Thermochim. Acta. 1992;197:147–160. doi: 10.1016/0040-6031(92)87046-D. DOI

Rodante F., Marrosu G., Catalani G. Thermal analysis of some α-amino acids with similar structures. Thermochim. Acta. 1992;194:197–213. doi: 10.1016/0040-6031(92)80018-R. DOI

Contineanu I., Neacşu A., Gheorghe D., Tănăsescu S., Perişanu Ş. The thermochemistry of threonine stereoisomers. Thermochim. Acta. 2013;563:1–5. doi: 10.1016/j.tca.2013.04.001. DOI

Moggach S.A., Clark S.J., Parsons S. L-Cysteine-I at 30 K. Acta Crystallogr. Sect. E. 2005;61:o2739–o2742. doi: 10.1107/S1600536805023688. DOI

Kerr K.A., Ashmore J.P., Koetzle T.F. A neutron diffraction study of l-cysteine. Acta Crystallogr. Sect. B. 1975;31:2022–2026. doi: 10.1107/S0567740875006772. DOI

Kistenmacher T.J., Rand G.A., Marsh R.E. Refinements of the crystal structures of dl-serine and anhydrous l-serine. Acta Crystallogr. Sect. B. 1974;30:2573–2578.

Shoemaker D.P., Donohue J., Schomaker V., Corey R.B. The Crystal Structure of Ls-Threonine1. J. Am. Chem. Soc. 1950;72:2328–2349. doi: 10.1021/ja01162a002. DOI

Torii K., Iitaka Y. Crystal structures and molecular conformations of l-methionine and l-norleucine. Acta Crystallogr. Sect. B. 1973;29:2799–2807. doi: 10.1107/S0567740873007569. DOI

Görbitz C.H., Karen P., Dušek M., Petříček V. An exceptional series of phase transitions in hydrophobic amino acids with linear side chains. IUCrJ. 2016;3:341–353. doi: 10.1107/S2052252516010472. PubMed DOI PMC

Paukov I., Kovalevskaya Y., Boldyreva E. Low-temperature thermodynamic properties of L -cysteine. J. Therm. Anal. Calorim. 2008;93:423–428. doi: 10.1007/s10973-007-8697-0. DOI

Lima J.A., Freire P.T.C., Melo F.E.A., Filho J.M., Fischer J., Havenith R.W.A., Broer R., Bordallo H.N. Using Raman spectroscopy to understand the origin of the phase transition observed in the crystalline sulfur based amino acid l-methionine. Vib. Spectrosc. 2013;65:132–141. doi: 10.1016/j.vibspec.2012.12.004. DOI

Guinet Y., Paccou L., Danède F., Hédoux A. Revisiting the phase transition sequence in L-methionine: Description of the disordering mechanism in an essential amino acid. J. Chem. Phys. 2022;156:034501. doi: 10.1063/5.0077743. PubMed DOI

Grunenberg A., Bougeard D., Schrader B. DSC-investigations of 22 crystalline neutral aliphatic amino acids in the temperature range 233 to 423 K. Thermochim. Acta. 1984;77:59–66. doi: 10.1016/0040-6031(84)87046-X. DOI

Hutchens J.O., Cole A.G., Stout J.W. Heat capacities and entropies of L-cystine and L-methionine: The transition of L-methionine near 305.5 °K. J. Biol. Chem. 1964;239:591–595. PubMed

Sabbah R., Minadakis C. Thermodynamics of sulfur compounds II. Thermochemical study of L-cysteine and L-methionine. Thermochim. Acta. 1981;43:269–277. doi: 10.1016/0040-6031(81)85184-2. DOI

Roux M.V., Notario R., Segura M., Chickos J.S., Liebman J.F. The enthalpy of formation of methionine revisited. J. Phys. Org. Chem. 2012;25:916–924. doi: 10.1002/poc.2961. DOI

Kerr K.A., Ashmore J.P. Structure and conformation of orthorhombic l-cysteine. Acta Crystallogr. Sect. B. 1973;29:2124–2127. doi: 10.1107/S0567740873006217. DOI

Harding M.M., Long H.A. The crystal and molecular structure of l-cysteine. Acta Crystallogr. Sect. B. 1968;24:1096–1102.

Moggach S.A., Allan D.R., Clark S.J., Gutmann M.J., Parsons S., Pulham C.R., Sawyer L. High-pressure polymorphism in l-cysteine: The crystal structures of l-cysteine-III and l-cysteine-IV. Acta Crystallogr. Sect. B. 2006;62:296–309. doi: 10.1107/S0108768105038802. PubMed DOI

Moggach S.A., Allan D.R., Morrison C.A., Parsons S., Sawyer L. Effect of pressure on the crystal structure of L-serine-I and the crystal structure of L-serine-II at 5.4 GPa. Acta Crystallogr. Sect. B. 2005;61:58–68. doi: 10.1107/S0108768104031787. PubMed DOI

Kolesnik E.N., Goryajnov S.V., Boldyreva E.V. Different behavior of the crystals of L- and DL-serine at high pressure. Transitions in L-serine and the stability of the phase of DL-serine. Dokl. Akad. Nauk. 2005;404:61–64.

Fisch M., Lanza A., Boldyreva E., Macchi P., Casati N. Kinetic Control of High-Pressure Solid-State Phase Transitions: A Case Study on l-Serine. J. Phys. Chem. C. 2015;119:18611–18617. doi: 10.1021/acs.jpcc.5b05838. DOI

Giordano N., Beavers C.M., Kamenev K.V., Marshall W.G., Moggach S.A., Patterson S.D., Teat S.J., Warren J.E., Wood P.A., Parsons S. High-pressure polymorphism in l-threonine between ambient pressure and 22 GPa. CrystEngComm. 2019;21:4444–4456. doi: 10.1039/C9CE00388F. DOI

Dalhus B., Görbitz C.H. Crystal Structures of Hydrophobic Amino Acids. I. Redeterminations of L-Methionine and L-Valine at 120 K. Acta Chem. Scand. 1996;50:544–548.

Khawas B. The unit cells and space groups of l-methionine, l-[beta]-phenylalanine and dl-tyrosine. Acta Crystallogr. Sect. B. 1970;26:1919–1922.

Huffman H.M., Ellis E.L. Thermal Data. III. The Heat Capacities, Entropies and Free Energies of Four Organic Compounds Containing Sulfur. J. Am. Chem. Soc. 1935;57:46–48. doi: 10.1021/ja01304a014. DOI

Hutchens J.O., Cole A.G., Stout J.W. Heat capacities from 11 to 305 °K., entropies, enthalpy, and free-energy formation of L-serine. J. Biol. Chem. 1964;239:4194–4195. doi: 10.1016/S0021-9258(18)91154-3. PubMed DOI

Cole A.G., Hutchens J.P., Robie R.A., Stout J.W. Apparatus and methods for low temperature heat-capacity measurements. Heat capacity of standard benzoic acid. J. Am. Chem. Soc. 1960;82:4807–4813. doi: 10.1021/ja01503a013. DOI

Varushchenko R.M., Druzhinina A.I., Sorkin E.L. Low-temperature heat capacity of 1-bromoperfluorooctane. J. Chem. Thermodyn. 1997;29:623–637. doi: 10.1006/jcht.1996.0173. DOI

Vojtíšková O., Štejfa V., Pokorný V., Růžička K., Fulem M. Heat capacities of selected active pharmaceutical ingredients II. J. Chem. Thermodyn. 2022 in preparation .

Höhne G., Hemminger W., Flammersheim H.J. Differential Scanning Calorimetry. Springer; Berlin, Germany: London, UK: 2003.

Suzuki Y.T., Yamamura Y., Sumita M., Yasuzuka S., Saito K. Neat liquid consisting of hydrogen-bonded tetramers: Dicyclohexylmethanol. J. Phys. Chem. B. 2009;113:10077–10080. doi: 10.1021/jp9048764. PubMed DOI

Lashley J.C., Hundley M.F., Migliori A., Sarrao J.L., Pagliuso P.G., Darling T.W., Jaime M., Cooley J.C., Hults W.L., Morales L., et al. Critical examination of heat capacity measurements made on a Quantum Design physical property measurement system. Cryogenics. 2003;43:369–378. doi: 10.1016/S0011-2275(03)00092-4. DOI

Shi Q., Snow C.L., Boerio-Goates J., Woodfield B.F. Accurate heat capacity measurements on powdered samples using a Quantum Design physical property measurement system. J. Chem. Thermodyn. 2010;42:1107–1115. doi: 10.1016/j.jct.2010.04.008. DOI

Arblaster J.W. Thermodynamic Properties of Copper. J. Phase Equilib. Diffus. 2015;36:422–444. doi: 10.1007/s11669-015-0399-x. DOI

Goursot P., Girdhar H.L., Westrum E.F. Thermodynamics of Polynuclear Aromatic Molecules.3. Heat Capacities and Enthalpies of Fusion of Anthracene. J. Phys. Chem. 1970;74:2538–2541.

Huffman H.M., Borsook H. Thermal data. I. The heat capacities, entropies and free energies of seven organic compounds containing nitrogen. J. Am. Chem. Soc. 1932;54:4297–4301. doi: 10.1021/ja01350a022. DOI

Hutchens J.O., Cole A.G., Stout J.W. Heat Capacities from 11 to 305 °K. and Entropies of l-Alanine and Glycine. J. Am. Chem. Soc. 1960;82:4813–4815. doi: 10.1021/ja01503a014. DOI

Mahnel T., Pokorný V., Fulem M., Sedmidubský D., Růžička K. Measurement of low-temperature heat capacity by relaxation technique: Calorimeter performance testing and heat capacity of benzo[b]fluoranthene, benzo[k]fluoranthene, and indeno[1,2,3-cd]pyrene. J. Chem. Thermodyn. 2020;142:105964. doi: 10.1016/j.jct.2019.105964. DOI

Archer D.G. Thermodynamic Properties of the NaCl + H2O System l. Thermodynamic Properties of NaCl(cr) J. Phys. Chem. Ref. Data. 1992;21:1–21.

Lukyanova V.A., Druzhinina A.I., Pimenova S.M., Ioutsi V.A., Buyanovskaya A.G., Takazova R.U., Sagadeyev E.V., Gimadeev A.A. Thermodynamic properties of l-tryptophan. J. Chem. Thermodyn. 2017;105:44–49. doi: 10.1016/j.jct.2016.09.041. DOI

Deiko Y.A., Il’in D.Y., Druzhinina A.I., Konstantinova N.M., Lukonina N.S., Dmitrienko A.O., Luk’yanova V.A. Thermodynamic Properties of L-Asparagine Monohydrate. Russ. J. Phys. Chem. A. 2022;96:1840–1848.

Cole A.G., Hutchens J.O., Stout J.W. Heat capacities from 11 to 305°K. and entropies of L-phenylalanine, L-proline, L-tryptophan, and L-tyrosine. Some free energies of formation. J. Phys. Chem. 1963;67:1852–1855.

Hutchens J.O., Cole A.G., Robie R.A., Stout J.W. Heat capacities from 11 to 305°K, entropies and free energies of formation of L-asparagine monohydrate, L-aspartic acid, L-glutamic acid, and L-glutamine. J. Biol. Chem. 1963;238:2407–2412. doi: 10.1016/S0021-9258(19)67985-8. PubMed DOI

Heat Capacities of α-, β-, and γ- Polymorphs of Glycine

Thermodynamic Study of N-Methylformamide and N,N-Dimethyl-Formamide

Heat Capacity of Indium or Gallium Sesqui-Chalcogenides

Heat Capacities of N-Acetyl Amides of Glycine, L-Alanine, L-Valine, L-Isoleucine, and L-Leucine