{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:16:41Z","timestamp":1760145401539,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Andalusian Government","award":["P18-RT-3786","PID2022-137603OB-I00","PID2021-127199NB-I00","PRE2022-101260","CIAICO\/2022\/121"],"award-info":[{"award-number":["P18-RT-3786","PID2022-137603OB-I00","PID2021-127199NB-I00","PRE2022-101260","CIAICO\/2022\/121"]}]},{"name":"Spanish Science and Innovation Ministry and European Social Fund Plus","award":["P18-RT-3786","PID2022-137603OB-I00","PID2021-127199NB-I00","PRE2022-101260","CIAICO\/2022\/121"],"award-info":[{"award-number":["P18-RT-3786","PID2022-137603OB-I00","PID2021-127199NB-I00","PRE2022-101260","CIAICO\/2022\/121"]}]},{"DOI":"10.13039\/501100003359","name":"Generalitat Valenciana","doi-asserted-by":"publisher","award":["P18-RT-3786","PID2022-137603OB-I00","PID2021-127199NB-I00","PRE2022-101260","CIAICO\/2022\/121"],"award-info":[{"award-number":["P18-RT-3786","PID2022-137603OB-I00","PID2021-127199NB-I00","PRE2022-101260","CIAICO\/2022\/121"]}],"id":[{"id":"10.13039\/501100003359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Tetroxane derivatives are interesting drugs for antileishmaniasis and antimalaric treatments. The gas-phase thermal decomposition of 3,6,-dimethyl-1,2,4,5-tetroxane (DMT) and 3,3,6,6,-tetramethyl-1,2,4,5-tetroxane (acetone diperoxide (ACDP)) was studied at 493\u2013543 K by direct gas chromatography by means of a flow reactor. The reaction is produced in the injector chamber at different temperatures. The resulting kinetics Arrhenius equations were calculated for both tetroxanes. Including the parent compound of the series 1,2,4,5-tetroxane (formaldehyde diperoxide (FDP)), the activation energy and frequency factors decrease linearly with the number of methyl groups. The reaction mechanisms of ACDP and 3,6,6-trimethyl-1,2,4,5-tetroxane (TMT) decomposition have been studied by means of the DFT method with the BHANDHLYP functional. Our calculations confirm that the concerted mechanism should be discarded and that only the stepwise mechanism occurs. The critical points of the singlet and triplet state potential energy surfaces (S- and T-PES) of the thermolysis reaction of both compounds have been determined. The calculated activation energies of the different steps vary linearly with the number of methyl groups of the methyl-tetroxanes series. The mechanism for the S-PES leads to a diradical O\u00b7\u00b7\u00b7O open structure, which leads to a C\u00b7\u00b7\u00b7O dissociation in the second step and the production of the first acetaldehyde\/acetone molecule. This last one yields a second C\u00b7\u00b7\u00b7O dissociation, producing O2 and another acetone\/acetaldehyde molecule. The O2 molecule is in the singlet state. A quasi-parallel mechanism for the T-PES from the open diradical to products is also found. Most of the critical points of both PES are linear with the number of methyl groups. Reaction in the triplet state is much more exothermic than the singlet state mechanism. Transitions from the singlet ground state, S0 and low-lying singlet states S1\u20133, to the low-lying triplet excited states, T1\u20134, (chemical excitation) in the family of methyl tetroxanes are also studied at the CASSCF\/CASPT2 level. Two possible mechanisms are possible here: (i) from S0 to T3 by strong spin orbit coupling (SOC) and subsequent fast internal conversion to the excited T1 state and (ii) from S0 to S2 from internal conversion and subsequent S2 to T1 by SOC. From these experimental and theoretical results, the additivity effect of the methyl groups in the thermolysis reaction of the methyl tetroxane derivatives is clearly highlighted. This information will have a great impact for controlling these processes in the laboratory and chemical industries.<\/jats:p>","DOI":"10.3390\/molecules29143274","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T11:33:22Z","timestamp":1720697602000},"page":"3274","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Kinetic Study and Reaction Mechanism of the Gas-Phase Thermolysis Reaction of Methyl Derivatives of 1,2,4,5-Tetroxane"],"prefix":"10.3390","volume":"29","author":[{"given":"Alexander G.","family":"Bord\u00f3n","sequence":"first","affiliation":[{"name":"Laboratorio de Investigaciones en Tecnolog\u00eda Ambiental, \u00c1rea de Qu\u00edmica F\u00edsica Facultad de Ciencias Exactas y Naturales y Agrimensura, Universidad Nacional del Nordeste, Av. Libertad 5460, Corrientes 3400, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariela I.","family":"Profeta","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaciones en Tecnolog\u00eda Ambiental, \u00c1rea de Qu\u00edmica F\u00edsica Facultad de Ciencias Exactas y Naturales y Agrimensura, Universidad Nacional del Nordeste, Av. Libertad 5460, Corrientes 3400, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge M.","family":"Romero","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaciones en Tecnolog\u00eda Ambiental, \u00c1rea de Qu\u00edmica F\u00edsica Facultad de Ciencias Exactas y Naturales y Agrimensura, Universidad Nacional del Nordeste, Av. Libertad 5460, Corrientes 3400, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda J.","family":"Jorge","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaciones en Tecnolog\u00eda Ambiental, \u00c1rea de Qu\u00edmica F\u00edsica Facultad de Ciencias Exactas y Naturales y Agrimensura, Universidad Nacional del Nordeste, Av. Libertad 5460, Corrientes 3400, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilian C.","family":"Jorge","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaciones en Tecnolog\u00eda Ambiental, \u00c1rea de Qu\u00edmica F\u00edsica Facultad de Ciencias Exactas y Naturales y Agrimensura, Universidad Nacional del Nordeste, Av. Libertad 5460, Corrientes 3400, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelly L.","family":"Jorge","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaciones en Tecnolog\u00eda Ambiental, \u00c1rea de Qu\u00edmica F\u00edsica Facultad de Ciencias Exactas y Naturales y Agrimensura, Universidad Nacional del Nordeste, Av. Libertad 5460, Corrientes 3400, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8612-3826","authenticated-orcid":false,"given":"C. Ignacio","family":"Sainz-D\u00edaz","sequence":"additional","affiliation":[{"name":"Instituto Andaluz de Ciencias de la Tierra, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Av. Las Palmeras 4, 18100 Armilla, Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0127-579X","authenticated-orcid":false,"given":"Juliana","family":"Cu\u00e9llar-Zuquin","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia Molecular, Universitat de Val\u00e8ncia, Apartado 22085, 46071 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6495-2770","authenticated-orcid":false,"given":"Daniel","family":"Roca-Sanju\u00e1n","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia Molecular, Universitat de Val\u00e8ncia, Apartado 22085, 46071 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2219-3566","authenticated-orcid":false,"given":"C\u00e9sar","family":"Viseras Iborra","sequence":"additional","affiliation":[{"name":"Instituto Andaluz de Ciencias de la Tierra, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Av. Las Palmeras 4, 18100 Armilla, Granada, Spain"},{"name":"Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Campus de Cartuja s\/n, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Grand","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Formation et de Recherche, Universit\u00e9 Grenoble Alpes, Commissariat \u00e1 l\u2019\u00c9nergy Atomique (CEA), Centre National de la Recherche Scientifique (CNRS), Institute for Nanoscience and Cryogenics-Syst\u00e8mes Mol\u00e9culaires et Nanomat\u00e9riaux por l\u2019\u00c9nergieset la Sant\u00e9 (INAC-SyMMES), 38000 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfonso","family":"Hern\u00e1ndez-Laguna","sequence":"additional","affiliation":[{"name":"Instituto Andaluz de Ciencias de la Tierra, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Av. Las Palmeras 4, 18100 Armilla, Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/app.2225","article-title":"Bulk polymerization of styrene catalyzed by biand tri-functional cyclic initiators","volume":"83","author":"Cerna","year":"2002","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6359","DOI":"10.1016\/j.bmcl.2010.09.113","article-title":"The structure and antimalarial activity of dispiro-1, 2, 4, 5-tetraoxanes derived from (+)-dihydrocarvone","volume":"20","author":"Dong","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1016\/j.bmcl.2007.12.069","article-title":"Synthesis, thermal stability, antimalarial activity of symmetrically and asymmetrically substituted tetraoxanes","volume":"18","author":"Atheaya","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3496","DOI":"10.1128\/AAC.00363-09","article-title":"Stability of peroxide antimalarials in the presence of human hemoglobin","volume":"53","author":"Creek","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/1521-4087(200209)27:4<209::AID-PREP209>3.0.CO;2-J","article-title":"Decomposition of a Multiperoxidic Compound: Triacetone Triperoxide (TATP)","volume":"27","author":"Oxley","year":"2002","journal-title":"Prop. Explos. Pyrotech."},{"key":"ref_6","first-page":"1","article-title":"Synthesis and phytotoxic profile of a new tetraoxane designed from a commercial auxin","volume":"43","author":"Barbosa","year":"2020","journal-title":"Quim. Nova"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.chemphys.2011.11.019","article-title":"Gas-phase thermolysis reaction of formaldehyde diperoxide. Kinetic study and theoretical mechanisms","volume":"39","author":"Jorge","year":"2012","journal-title":"Chem. Phys."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1007\/s00894-014-2224-6","article-title":"Theoretical study of the gas-phase thermolysis of 3-methyl-1, 2, 4, 5-tetroxane","volume":"2","author":"Profeta","year":"2014","journal-title":"J. Mol. Model."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s00894-019-4092-6","article-title":"Theoretical study of the gas-phase thermolysis reaction of 3, 6-dimethyl-1, 2, 4, 5-tetroxane. Methyl and axial-equatorial substitution effects","volume":"25","author":"Pila","year":"2019","journal-title":"J. Mol. Model."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1007\/s10593-010-0449-6","article-title":"Thermal decomposition reaction of 3, 3, 6, 6- tetramethyl- 1, 2, 4, 5- tetroxane in 2-methoxy-ethanol solution","volume":"45","author":"Leiva","year":"2010","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5404","DOI":"10.1021\/ct4007844","article-title":"Revisiting the nonadiabatic process in 1, 2-dioxetane","volume":"9","author":"Farahani","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3334","DOI":"10.1021\/jo01272a072","article-title":"A convenient gas chromatographic method for determining activation energies of first-order reactions","volume":"33","author":"Schmigel","year":"1968","journal-title":"J. Org. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1002\/kin.550260503","article-title":"Kinetics and Mechanism of the Thermal Decomposition Reaction of Acetone Cyclic Diperoxide in the Gas Phase","volume":"26","author":"Cafferata","year":"1994","journal-title":"Int. J. Chem. Kin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7525","DOI":"10.1021\/ja00831a022","article-title":"Kinetics of the thermal decomposition of 3, 3-diphenyl- and 3, 3-dibenzyl-1, 2-dioxetane. Consideration of stepwise and concerted mechanisms","volume":"96","author":"Richardson","year":"1974","journal-title":"J. Am. Chem. Soc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1021\/ja00288a022","article-title":"Effects of methylation on the thermal stability and chemiluminescence properties of 1, 2-dioxetanes","volume":"107","author":"Adam","year":"1985","journal-title":"J. Am. Chem. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1126\/science.117.3039.340","article-title":"Parameters for the Description of Transition States","volume":"117","author":"Lefller","year":"1953","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1021\/ja01607a027","article-title":"A Correlation of Reaction Rates","volume":"77","author":"Hammond","year":"1955","journal-title":"J. Am. Chem. Soc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1021\/ar50001a002","article-title":"Triplet state. Its radiative and nonradiative properties","volume":"1","year":"1968","journal-title":"Acc. Chem. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3790","DOI":"10.1021\/acs.jpclett.7b01668","article-title":"How Do Methyl Groups Enhance the Triplet Chemiexcitation Yield of Dioxetane?","volume":"8","author":"Vacher","year":"2017","journal-title":"J. Phys. Chem. Lett."},{"key":"ref_20","unstructured":"Frisch, M.J., Truck, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Mennucci, B., and Petersson, G.A. (2009). Gaussian 09, Revision B.01, Gaussian Inc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1103\/PhysRevA.38.3098","article-title":"Density-functional exchange-energy approximation with correct asymptotic behavior","volume":"38","author":"Becke","year":"1988","journal-title":"Phys. Rev. A"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1063\/1.3129035","article-title":"Quantum Theory of Molecules and Solids Vol. 4: The Self-Consistent Field for Molecules and Solids","volume":"27","author":"Slater","year":"1974","journal-title":"Phys. Today"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1103\/PhysRevB.37.785","article-title":"Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density","volume":"37","author":"Lee","year":"1988","journal-title":"Phys. Rev. B"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1002\/jcc.540030212","article-title":"Optimization of Equilibrium Geometries and Transition Structures","volume":"3","author":"Schlegel","year":"1982","journal-title":"J. Comput. Chem."},{"key":"ref_25","unstructured":"Frisch, A., Nielsen, A.B., and Holder, A.J. (2001). Gauss View Molecular Visualization Program, Gaussian Inc.. User Manual."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1063\/1.456010","article-title":"An improved algorithm for reaction path following","volume":"90","author":"Gonzalez","year":"1989","journal-title":"J. Chem. Phys."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5523","DOI":"10.1021\/j100377a021","article-title":"Reaction Path Following in Mass-Weighted Internal Coordinates","volume":"94","author":"Gonzalez","year":"1990","journal-title":"J. Phys. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5483","DOI":"10.1021\/j100377a012","article-title":"Second-order perturbation theory with a CASSCF reference function","volume":"94","author":"Andersson","year":"1990","journal-title":"J. Phys. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/wcms.97","article-title":"Multiconfiguration second-order perturbation theory approach to strong electron correlation in chemistry and photochemistry","volume":"2","author":"Aquilante","year":"2012","journal-title":"Wiley Interdiscip. Rev. Comput. Mol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1002\/jcc.24221","article-title":"MOLCAS 8: New capabilities for multiconfigurational quantum chemical calculations across the periodic table","volume":"37","author":"Aquilante","year":"2016","journal-title":"J. Comput. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/S0009-2614(97)00669-6","article-title":"Multiconfiguration perturbation theory with imaginary level shift","volume":"274","author":"Forsberg","year":"1997","journal-title":"Chem. Phys. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0009-2614(89)85347-3","article-title":"The CASSCF state interaction method","volume":"155","author":"Malmqvist","year":"1989","journal-title":"Chem. Phys. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S0009-2614(02)00498-0","article-title":"The restricted active space (RAS) state interaction approach with spin\u2013orbit coupling","volume":"357","author":"Malmqvist","year":"2002","journal-title":"Chem. Phys. Lett."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/14\/3274\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:13:17Z","timestamp":1760109197000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/14\/3274"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,11]]},"references-count":33,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["molecules29143274"],"URL":"https:\/\/doi.org\/10.3390\/molecules29143274","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2024,7,11]]}}}