{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T16:46:58Z","timestamp":1775753218740,"version":"3.50.1"},"reference-count":61,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2020,3,19]],"date-time":"2020-03-19T00:00:00Z","timestamp":1584576000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Comput Chem"],"published-print":{"date-parts":[[2020,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Therapeutic efficiency of amphiphilic methotrexate\u2013camptothecin (MTX\u2010CPT) prodrug compared to free drug mixture (MTX\/CPT) has been investigated using all\u2010atom molecular dynamics simulation and first principles density functional theory calculations. This comparison revealed that MTX\u2013CPT prodrug tends to form spherical self\u2010assembled nanoparticle (NP), while free MTX\/CPT mixture forms rod\u2010shape NP. These observations are attributed to a structural defect in the MTX\u2013CPT prodrug and solvation free energies of MTX, CPT and MTX\u2010CPT molecules. The results provided evidence that noncovalent interactions (NCIs) among the pharmaceutical drugs play a very important role in anticancer agents aggregation process, leading to enhanced stability of the self\u2010assembled NPs. It is found that the stability of MTX\u2013CPT self\u2010assembled NP is greater than the MTX\/CPT NP due to the synergistic effect of hydrogen bonding between monomers and solvent (water). Moreover, the noncatalyzed as well as catalyzed hydrolysis reactions of MTX\u2013CPT prodrug are theoretically studied at the PCM(water)\/\/M06\u20102X\/6\u221231G(d,p) computational level to shed additional light on the role of acidic condition in tumor tissues. We found that the ester hydrolysis in mild acidic solutions is a concerted reaction. In an agreement between theory and experiment, we also confirmed that the activation energies of the catalyzed\u2010hydrolysis steps are much lower than the activation energies of the corresponding steps in the noncatalyzed reaction. Thus, the MTX\u2013CPT prodrug reveals very promising properties as a pH\u2010controlled drug delivery system.<\/jats:p>","DOI":"10.1002\/jcc.26192","type":"journal-article","created":{"date-parts":[[2020,3,19]],"date-time":"2020-03-19T12:06:32Z","timestamp":1584619592000},"page":"1486-1496","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Evaluation the synergistic antitumor effect of methotrexate\u2013camptothecin codelivery prodrug from self\u2010assembly process to acid\u2010catalyzed both drugs release: A comprehensive theoretical study"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9687-4209","authenticated-orcid":false,"given":"Majid","family":"Pakdel","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science University of Birjand  Birjand Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidar","family":"Raissi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science University of Birjand  Birjand Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyede T.","family":"Hosseini","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science University of Birjand  Birjand Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,3,19]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"1","volume":"9999","author":"Abbaspour M.","year":"2019","journal-title":"J. Comput. Chem."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.24920"},{"key":"e_1_2_8_4_1","first-page":"1","volume":"9999","author":"Pakdel M.","year":"2019","journal-title":"J. Biomol. Struct. Dyn."},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.7b10027"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6OB01815G"},{"key":"e_1_2_8_7_1","first-page":"731","volume":"81","author":"Sverdlov E. D.","year":"2016","journal-title":"Biochem."},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5RA17230F"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168960"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.20949"},{"key":"e_1_2_8_11_1","volume-title":"The Organic Chemistry of Drug Design and Drug Action","author":"Silverman R. B.","year":"2004"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-29870-0"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S166402"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S198353"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.langmuir.8b02710"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.8b20810"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.7b07132"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsabm.8b00056"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-809717-5.00015-4"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2018.11.032"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2019.102066"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep21225"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep12023"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13346-018-0502-z"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.10.061"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.7b01032"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.09.027"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2013.07.025"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/ma200675w"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5RA19508J"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.8b00116"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9NJ00269C"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2019.118491"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11467-017-0693-7"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2cp41395g"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep34647"},{"key":"e_1_2_8_37_1","unstructured":"T. W. G.Solomons Organic Chemistry 5th ed John Wiley New York 1992."},{"key":"e_1_2_8_38_1","unstructured":"H. B. Watson Modern Theories of Organic Chemistry Oxford University Press Oxford 1949."},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1039\/tf9413700686"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5CP02914G"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01148a063"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1039\/p29860000721"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9CP00444K"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8NJ02021C"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.8b00354"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8CP05749D"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp107516k"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.softx.2015.06.001"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21816"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar700111a"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.470117"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21224"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.2408420"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.328693"},{"key":"e_1_2_8_55_1","volume-title":"Gaussian 03, Revision c. 02","author":"Frisch M. J.","year":"2004"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct100641a"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/0263-7855(96)00018-5"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr960149m"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/sigtrans.2016.47"},{"key":"e_1_2_8_60_1","first-page":"1","volume":"9999","author":"Emamian S.","year":"2019","journal-title":"J. Comput. Chem."},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2946-4-17"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp810292n"}],"container-title":["Journal of Computational Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcc.26192","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcc.26192","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcc.26192","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcc.26192","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T06:20:51Z","timestamp":1693981251000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcc.26192"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,19]]},"references-count":61,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2020,6,15]]}},"alternative-id":["10.1002\/jcc.26192"],"URL":"https:\/\/doi.org\/10.1002\/jcc.26192","archive":["Portico"],"relation":{},"ISSN":["0192-8651","1096-987X"],"issn-type":[{"value":"0192-8651","type":"print"},{"value":"1096-987X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,19]]},"assertion":[{"value":"2019-09-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}