{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T14:51:20Z","timestamp":1767192680501,"version":"build-2065373602"},"reference-count":99,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2015,2,18]],"date-time":"2015-02-18T00:00:00Z","timestamp":1424217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Inorg Chem"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The need for magnetic resonance imaging (MRI) contrast agents with improved relaxivity maintains the development of new Gd<jats:sup>III<\/jats:sup> chelates as an intensive and demanding field of research. In this work, we introduce the new dimeric chelators bis{1,4,7,10\u2010tetraazacyclododecane\u20101\u2010[(6\u2010amino)hexanoic]\u20104,7,10\u2010triacetic acid}adipate [<jats:bold>L2<\/jats:bold>, bis(DOTA\u2010AHA)adipate] and bis{1,4,7,10\u2010tetraazacyclododecane\u20101\u2010[(6\u2010amino)hexanoic]\u20104,7,10\u2010triacetic acid}1,3\u2010phenyldiacetate [<jats:bold>L3<\/jats:bold>, bis(DOTA\u2010AHA)1,3\u2010phenyldiacetate], which are based on the bifunctional ligand 1,4,7,10\u2010tetraazacyclododecane\u20101\u2010[(6\u2010amino)hexanoic]\u20104,7,10\u2010triacetic acid (<jats:bold>L1<\/jats:bold>, DOTA\u2010AHA). Their Gd<jats:sup>III<\/jats:sup> chelates were studied by variable\u2010temperature <jats:sup>1<\/jats:sup>H nuclear magnetic relaxation dispersion (NMRD) and <jats:sup>17<\/jats:sup>O NMR spectroscopy to measure their relaxivities and the parameters that govern them. The rates of exchange of inner\u2010sphere water from the monomer Gd<jats:bold>L1<\/jats:bold> and from the two dinuclear chelates Gd<jats:sub>2<\/jats:sub><jats:bold>L2<\/jats:bold> and Gd<jats:sub>2<\/jats:sub><jats:bold>L3<\/jats:bold> are very similar (<jats:sup>298<\/jats:sup><jats:italic>k<\/jats:italic><jats:sub>ex<\/jats:sub> \u2248 6.5\u2009\u00d7\u200910<jats:sup>6<\/jats:sup> s<jats:sup>\u20131<\/jats:sup>) and slightly faster than that for [Gd(DOTA)H<jats:sub>2<\/jats:sub>O]<jats:sup>\u2013<\/jats:sup> (<jats:sup>298<\/jats:sup><jats:italic>k<\/jats:italic><jats:sub>ex<\/jats:sub> = 4.1\u2009\u00d7\u200910<jats:sup>6<\/jats:sup> s<jats:sup>\u20131<\/jats:sup>). All three compounds form weakly bound aggregates with equilibrium constants <jats:sup>298<\/jats:sup><jats:italic>K<\/jats:italic> of 2.9, 15.6, and 14.6 for Gd<jats:bold>L1<\/jats:bold>, Gd<jats:sub>2<\/jats:sub><jats:bold>L2<\/jats:bold>, and Gd<jats:sub>2<\/jats:sub><jats:bold>L3<\/jats:bold>, respectively. Even though the aggregates contain only 10 to 15\u2009% of the total amount of Gd<jats:sup>III<\/jats:sup> ions, a marked increase in relaxivity between 30 and 100 MHz is observed. Furthermore, the distance between the two Gd<jats:sup>III<\/jats:sup> centers in the dinuclear compounds has been determined by double electron\u2013electron resonance (DEER) spectroscopy experiments and by molecular modeling studies, which afforded comparable distances. The linkers between the chelating moieties allow Gd<jats:sup>III<\/jats:sup>\u2013Gd<jats:sup>III<\/jats:sup> distances of ca. 3.0 nm for the completely stretched linker conformation and less than 1.9 nm for the conformation with the metal centers at a closer distance. These metal\u2010to\u2010metal distances by themselves cannot explain the considerably long tumbling times of the chelates in solution. Only a model consistent with some level of aggregation for the dinuclear chelates in aqueous solution could satisfactorily explain our results.<\/jats:p>","DOI":"10.1002\/ejic.201403159","type":"journal-article","created":{"date-parts":[[2015,2,18]],"date-time":"2015-02-18T06:07:19Z","timestamp":1424239639000},"page":"1579-1591","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Dinuclear DOTA\u2010Based Gd<sup>III<\/sup> Chelates \u2013 Revisiting a Straightforward Strategy for Relaxivity Improvement"],"prefix":"10.1002","volume":"2015","author":[{"given":"Andr\u00e9","family":"Fontes","sequence":"first","affiliation":[]},{"given":"Shima","family":"Karimi","sequence":"additional","affiliation":[]},{"given":"Lothar","family":"Helm","sequence":"additional","affiliation":[]},{"given":"Maxim","family":"Yulikov","sequence":"additional","affiliation":[]},{"given":"Paula M.","family":"Ferreira","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o P.","family":"Andr\u00e9","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2015,2,18]]},"reference":[{"volume-title":"Biomedical Uses of Radiation","year":"1999","author":"Birn R. M.","key":"e_1_2_6_1_2"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-72718-7"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-45733-X_3"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmmi.327"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr980440x"},{"key":"e_1_2_6_6_2","unstructured":"\u00a0"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.04.018"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1039\/b719704g"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules18089352"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnmrs.2006.03.003"},{"key":"e_1_2_6_11_2","unstructured":"\u00a0"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/ic0200390"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/ic050743r"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1039\/b518147j"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0777990"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja1099616"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1039\/c0dt01370f"},{"key":"e_1_2_6_18_2","unstructured":"\u00a0"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-458X(199805)36:5<376::AID-OMR269>3.0.CO;2-S"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/mp060072i"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/bc060014f"},{"key":"e_1_2_6_22_2","unstructured":"\u00a0"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/mp050019e"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2005.09.016"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1039\/b616960k"},{"key":"e_1_2_6_26_2","unstructured":"\u00a0"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-3765(19991001)5:10<2977::AID-CHEM2977>3.0.CO;2-T"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-002-0353-3"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.1011"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2010.10.003"},{"key":"e_1_2_6_31_2","unstructured":"\u00a0"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0677867"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/bc7001715"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00249-008-0331-y"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.200500969"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004424-199811000-00002"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rcl.2009.05.003"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.21966"},{"key":"e_1_2_6_39_2","unstructured":"\u00a0"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007750050320"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(00)00413-3"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2006.08.019"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1039\/b912201j"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004424-199809000-00026"},{"key":"e_1_2_6_45_2","unstructured":"\u00a0"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/bc00035a017"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja309187m"},{"key":"e_1_2_6_48_2","unstructured":"\u00a0"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1021\/ic00038a023"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja961743g"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1021\/ic951492x"},{"key":"e_1_2_6_52_2","unstructured":"\u00a0"},{"key":"e_1_2_6_53_2","first-page":"3780","author":"Kenwright A. M.","year":"2003","journal-title":"Dalton Trans."},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1039\/C2DT32009F"},{"key":"e_1_2_6_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-8838(05)57002-8"},{"key":"e_1_2_6_56_2","unstructured":"\u00a0"},{"key":"e_1_2_6_57_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00381a009"},{"key":"e_1_2_6_58_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00381a010"},{"key":"e_1_2_6_59_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007750000193"},{"key":"e_1_2_6_60_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-013-1036-y"},{"volume-title":"The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging","year":"2013","author":"T\u00f3th E.","key":"e_1_2_6_61_2"},{"key":"e_1_2_6_62_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00843a025"},{"key":"e_1_2_6_63_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00892a016"},{"key":"e_1_2_6_64_2","unstructured":"\u00a0"},{"key":"e_1_2_6_65_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.200501335"},{"key":"e_1_2_6_66_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201301231"},{"key":"e_1_2_6_67_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmmi.100"},{"key":"e_1_2_6_68_2","unstructured":"\u00a0"},{"key":"e_1_2_6_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-2614(84)80148-7"},{"key":"e_1_2_6_70_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmre.1999.1944"},{"key":"e_1_2_6_71_2","unstructured":"\u00a0"},{"key":"e_1_2_6_72_2","doi-asserted-by":"publisher","DOI":"10.1039\/b614920k"},{"key":"e_1_2_6_73_2","doi-asserted-by":"publisher","DOI":"10.1017\/S003358350700460X"},{"key":"e_1_2_6_74_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5288.768"},{"key":"e_1_2_6_75_2","unstructured":"\u00a0"},{"key":"e_1_2_6_76_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja075544g"},{"key":"e_1_2_6_77_2","doi-asserted-by":"publisher","DOI":"10.1021\/jz200073h"},{"key":"e_1_2_6_78_2","doi-asserted-by":"publisher","DOI":"10.1039\/c3cp53822b"},{"volume-title":"Electron Paramagnetic Resonance: Volume 24","year":"2015","author":"Yulikov M.","key":"e_1_2_6_79_2"},{"volume-title":"Structure and Bonding","year":"2013","author":"Jeschke G.","key":"e_1_2_6_80_2"},{"key":"e_1_2_6_81_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03166213"},{"key":"e_1_2_6_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmr.2010.03.019"},{"key":"e_1_2_6_83_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo971176v"},{"key":"e_1_2_6_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2364(82)90147-0"},{"key":"e_1_2_6_85_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmre.2001.2298"},{"key":"e_1_2_6_86_2","unstructured":"\u00a0"},{"key":"e_1_2_6_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmr.2009.06.007"},{"key":"e_1_2_6_88_2","doi-asserted-by":"publisher","DOI":"10.1039\/c2cp41520h"},{"key":"e_1_2_6_89_2","doi-asserted-by":"publisher","DOI":"10.1002\/hlca.19590420622"},{"key":"e_1_2_6_90_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrc.922"},{"key":"e_1_2_6_91_2","unstructured":"\u00a0"},{"key":"e_1_2_6_92_2","doi-asserted-by":"publisher","DOI":"10.1002\/hlca.19850680224"},{"key":"e_1_2_6_93_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRev.99.559"},{"key":"e_1_2_6_94_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.1669699"},{"key":"e_1_2_6_95_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.1716296"},{"key":"e_1_2_6_96_2","unstructured":"\u00a0"},{"key":"e_1_2_6_97_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.1743771"},{"key":"e_1_2_6_98_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.1731684"},{"key":"e_1_2_6_99_2","unstructured":"F. Yerly Visualiseur\/Optimiseur \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne Switzerland 2003."}],"container-title":["European Journal of Inorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fejic.201403159","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejic.201403159","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ejic.201403159","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejic.201403159","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T11:02:04Z","timestamp":1760353324000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/ejic.201403159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,18]]},"references-count":99,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1002\/ejic.201403159"],"URL":"https:\/\/doi.org\/10.1002\/ejic.201403159","archive":["Portico"],"relation":{},"ISSN":["1434-1948","1099-0682"],"issn-type":[{"type":"print","value":"1434-1948"},{"type":"electronic","value":"1099-0682"}],"subject":[],"published":{"date-parts":[[2015,2,18]]},"assertion":[{"value":"2014-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}