CINXE.COM

<!DOCTYPE html><html lang="en-US"><head><title>Just a moment...</title><meta http-equiv="Content-Type" content="text/html; charset=UTF-8"><meta http-equiv="X-UA-Compatible" content="IE=Edge"><meta name="robots" content="noindex,nofollow"><meta name="viewport" content="width=device-width,initial-scale=1"><style>*{box-sizing:border-box;margin:0;padding:0}html{line-height:1.15;-webkit-text-size-adjust:100%;color:#313131;font-family:system-ui,-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Helvetica Neue,Arial,Noto Sans,sans-serif,Apple Color Emoji,Segoe UI Emoji,Segoe UI Symbol,Noto Color Emoji}body{display:flex;flex-direction:column;height:100vh;min-height:100vh}.main-content{margin:8rem auto;max-width:60rem;padding-left:1.5rem}@media (width <= 720px){.main-content{margin-top:4rem}}.h2{font-size:1.5rem;font-weight:500;line-height:2.25rem}@media (width <= 720px){.h2{font-size:1.25rem;line-height:1.5rem}}#challenge-error-text{background-image:url(data:image/svg+xml;base64,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);background-repeat:no-repeat;background-size:contain;padding-left:34px}@media (prefers-color-scheme:dark){body{background-color:#222;color:#d9d9d9}}</style><meta http-equiv="refresh" content="390"></head><body class="no-js"><div class="main-wrapper" role="main"><div class="main-content"><noscript><div class="h2"><span id="challenge-error-text">Enable JavaScript and cookies to continue</span></div></noscript></div></div><script>(function(){window._cf_chl_opt={cvId: '3',cZone: "pubs.acs.org",cType: 'managed',cRay: '9137e879694afd3f',cH: 'QXGZ6H.VVzgbR9TqfpI3B4ILJfDHeD0VKVK6GwW5CaY-1739817650-1.2.1.1-TKvvsjITAevo0YAXg9_5z1arQUqs64UIhHcp7I4ffCArRNw8KYA9Nld1JoGScP2r',cUPMDTk: "\/doi\/10.1021\/acs.jmedchem.5b00698?__cf_chl_tk=Cs1_oTAFogPfCMxJLOxkP9gzY6m8XbsRdCrzNQb4D9E-1739817650-1.0.1.1-FyzdGxGGsBKsUlYjwEKHCN0WYSt2Vt3YXPFxy.64FIY",cFPWv: 'g',cITimeS: '1739817650',cTTimeMs: '1000',cMTimeMs: '390000',cTplC: 0,cTplV: 5,cTplB: 'cf',cK: "",fa: "\/doi\/10.1021\/acs.jmedchem.5b00698?__cf_chl_f_tk=Cs1_oTAFogPfCMxJLOxkP9gzY6m8XbsRdCrzNQb4D9E-1739817650-1.0.1.1-FyzdGxGGsBKsUlYjwEKHCN0WYSt2Vt3YXPFxy.64FIY",md: "Shqevg_ETzMeqkQejLntu1bHYmSZJ8fQxzFXFOaZlJ4-1739817650-1.2.1.1-3S.M4yFWY5TxCg1BFIdig9BDqwDAbkjObLVffA2CJPiPYqpaEKMVNqEzWaIbS2rbhUfobyCY.1SyyBMcjVesTqyHC_clMa52wyisaHWQk8S5qXMg7Xp_5nJ8RhbuuSOwhl90FiFqUSz_hXq3XU3aAihBFhdoREL04_aYwpCc3L3lTkn806oD2bhZDVhpxMsytAut9ScXB7xtz2OYlt7jZCxNGyp0frv9Rbx0NHoWIk3na6.UKCxxOeB1lAfL17cBMj7Ch4BA03i2hCVY0ln8D.Oof281jUX9BEBwkP6Wi5ZHcyjNlq.ICr_8s2t4amq.6V4sJ1ljvZZB2i2XQYzzvIhvMzpYo30prsK3UkP69xJbaaTYLBVrOJJovS_URyGy8VsGBhOwtGt9qKQSheKRYhCMZAT0JBkkXMVGFsSKnJrQxmoz4IdRr2YxO56lrIMUNO912DSxTnM.DgWfhOggoj08Z3TYlMSLXMWN6nkLp6Q67YYV1bC677e_2SkwoTvo_YiN_oWpBO5tJBfCtpczHJ_KKoE9jrZUBBIy7oQZeqFX77Y9SwJD3lewXCdv10CO807WRZ5F1LIvWlpjpTPEbyY2p.ZwwBFCajrrUnzVga_8EAz3IrgfCHvMkO1dhCecyGBGolGbMBLlTZli337i2BzjeoTjS0YC65VSo2Pj8juKx4nNuN_tcmNqhAR_vlUYhqoND8hufMSYuhuZK4PYoKCPWON_.rHcqat_wbmy2QJZr7eNpVF_dGrBklPHfxl84rSh7Bm3C3634b42A_kh.F1z6aCQsJcnRnQ59Q4OV4SrwOXf8RJ1VDNxWTjpsCV_WU657XBs.fjzo0MDrCQsaPmzxHBq81LuIuT6DiAI0fumZVBpnTVZREahSGqZMW_kkv5v0Lpt8y26EZzdNX6QMG3Gk.x5LaxsLkQXIIMwQo6SYpctAPSyBtp9rKyHxiRbxjrlYOd_qwVsIrUsZo5LCsqjrgm9_t.Vdd0hx6veHIDfePvmN3wI.D1mEN9MH4Xe85SkKATCm_W.KZ3FMJMMVA7p0wqI.YOOkWhmA.tyfkT1PXfWq0WTMBflswEI5Jm0B8FYfFB.wuwkMMEK3DBXz3xclGErNOVwdiFqpxxhossfLymBJCfLe8FnlYyhf4JnzIDPTAg25iTFWOeJBPil6MH0t4U.jTPSAVMFu9.Qeq82JCmJ21iTicRG9Y6fd6XDHxfsREyNNXkNY.v9H7Ywd6LB0mHESVxq0fM_FELZZym7qDBkHgpf5C2ELmSfhHCcYIiaWGvQ8RCZ.P8VuVvi5eroTAFfn13vbp89QCNiTgoxIEvpddZXLkFLrReHfRZCQvvewClRue0P7YjvmiBOOZzNDnWqc8T2nHPHwf9AYhI1xTDe37jqLeiU4ZSx6DythfddVBa5EQ3qt4gaCWpunu.Q7v2s54d82Hn.I_vsD3AVqI2X8lgK1Xk7F45b46BnrY2a45ZZwzeNvJY4uOKQZ4HVfauhAqpiy5tg93ZMiyTgSgFw3qW1Zn._8A_AIlrdvXw4EnM890N1ic1qlbjqFpII5UMRx42UyoxhajpoQYxhbKDUHgEkX4l2zhHCbu_e__Dkh6a1DKdZ.DFeR2mFrtDxabkqVR0J2DtAzV2juwZ5vYP_ZzhcNGLx126uJGDATel.wftoo_JX08p0JPYQEEsN7yvQZK9lQ5_zff05kIjEaPKJUbFXrzRGKoKt7J2edyJBmAAqmC1h9.x7XFMcJGRO9et3_oodZX..hXl4Wg5BJul_uvsle8nuWJkvERtNSpDjwmG4p8rOTWhs48HShHPmZlJ0r2PS9gBdLHcu1lx5bqTiCQOmJzSikUd3wNP0WYQkjqiB3dSWt48jO4R8wDxYk5xa4HkSR0kzwqUOzrX5qVuEO2mrMw4_cRtOVMNaxFGv28jCfLhgosDc4RRvjYljGf.68j5BoDZM7xCzNT.zPaBMC9iq0VyD0UarQ2j1GXrxl40D.69ohqVPgfunIFBO4NpZObksfPyNENJ1eOxupObGRKHaYzPjHL0oZzwqhUuqFzP8cVlTzL08Twdpc_8tWDFlfxnm3fzwvFPLCbk5BwmbAt4mg0GaEmy7guwvnxX.OtVCwMkbBU_kIO5sfTbp_2QNz_yquOEPb.30EU1Sx6RO6w1Ga7sLyf5xvjBiCg62UVvf1hEkPpxtu3Q_2G_ihnRqZSOKALD77yoCh3ZOWDVN2tYtWt.jjyoFGbopLY._xprOnCtwCG_HxOFwt4BLFu5dAuj8ckcaqeKc3BznVjAG7Sr_xJUPT2hx3.OWK30zqEUVjNMIWx8FvUErJcL_pe8tJfsdQqtUtOIRjGw6zCsclqAN6mYAVk8jC2z5dlQxcw6AWi5Q92Uq.RtmTbNVDtwagCe2aRtM18y5kE9ZZ8ofNAYmjDZcpF1YIl.alER6fAtz55PbUBsMSMmuuZdHROwLdzrZgJKIjlGxlDF7V0rAwlvLiVpxq_26ba3DOtYY4U6Gbi6uZ0EWdaZJGJpm00NMbsmDJzbV2xfpz3byr8Db1uUtOa2h1IteNvsu6qR_TzC0l_gUk00JZglG0pYIZZzJjnO49dJ7l4cfqwA",mdrd: "jck9BkgkW5vFwUponWM0HSkdZ63SZ9FREqSaUP0Vdyk-1739817650-1.2.1.1-7JWbrG55alaq78zxVMgOm2GQa3fOp3e865leYrW3HQjvPb6u8s1tITHPj.8qpk67v7MTlK9ZD283xK0uiU88BwvC0ZUjhjpVa_4ysziKqOoOjz2Zbzy8cs.AtwY.MFXWQxAzDyIRaA2Ix5FiPcz6PKw8i2oDXfXcCVK.daWp._CsitjqcaawhXbTlj9mls8i47pV0FeqP.0U3sWcVl6WXhSlrbVM0ryc1CSPZVQcL4HUYdk4cnroPCyX22PWIrLR_tYYIINcD4Gbv_xQEFtFhHrsRenqRV2V9hijqsrDqTuPIC8L_8VjM9vnf9NZgH77.e8mY_ZJDoJeEsasZMZIsB30Azc9yxfZNJnXnenw5gqhI0gaXAk5b5fontvYqeb0C79HGJHNAFxwRbjlsg05BsohgaSoI672H5ffMRNWjKc5Tnur_k9qgxNy0QEDxlX6I4U5ZG4Fhx6uweL9OUY6DEkFM.7ayP6x8oMt4b3XtVQUikfyBniJ4oxcORUAVMbYogepU7Zw11ZqR3uDxIM7NP.k7BD.sbC37ejMZNkMHqR_car54FKR.1651GfDqyCO7R.XvMb226v9h9jUnCeCI38tT6USsy1oBKCcoEGdogf8LtDq7uEwhLAaNbUwyyNNB4hixJW1Yl.67XXgp2UM.BtCLpscXjfCFH9UICsqr1RQ4ItJkfq77FwhFktej_Q8nZzmw.Cafv6WS0LT72N6r.MN5R4b7g_3o6sUmk9IGwD9DKgYAOzcNuUrW8ogWOE3fjzfEoer5GCGhXi1NDh6V3z.aStmuz7WGhnKJE29g6FdQFl7JfYuJdPDKwubGIq_rGax0ICV7.iGcMfwKzMw.0b3FE1phggAYA43XBhIQQa0SRQ0deIg9bG4NrlgXqpKxkpSCdkqZw109uKEwostjM3B26JhfmMw3Io6AVt5Vr9UrMqyuwzJ5cRPU0QvrH8MrlPlrQo7g56CA_jlkLeH6V6.1k1HEK59ZbycmAq0YV0xY_VI5SCuE3A5xipkFrE4TY0HIfH1L4lKjdO2YALxYeYaOfpwxP7EjsOAzdpNdeO0wMZ..rrtVlf_64euWF98yTadgT4XjGLIIEQmIL6vsHj25KdDCPJd9bjaFU3rlyW9Oqlt1D8ssao0C5klkndIQALFF4b9emXpGp5dtu.WA92YX7xoYs4Vhl3aF4nawfdvp76DypAZJ3jGfK.UnAs503w12eNcOPAfsIwJFkG_kva7RRSYF7yMsyU.NjRPN_7V9xX9pJAy6UxHz8Au6jvZ2zTagzS4E1_.LD46ZbWbr.ruC3CsfGR.dSyO603nAYalk.zsOp.ygqr0pCygKubfMUHKzymfT6FVM71o6TeQjEgYaLboyGIr0tbC9GrW2BOCaD7roR75hfBZ8RyUXic2ZxP5HQV7T_lTrUNo6_BsD2dJz2D82YL5Fxvi8ojmSOUgfOdO7fgCtHMpNSDVAuCIXYKEzGU4JzXgpDDbD.cPfrra8590SfpcsehR_k2yxEBreVUKRtqX4OZc1eq2YcpIHfTnHaEWblRjY3No8fk1j4fOXoWRhfxCAnFPq9LX.Y_F4_KzV2XpZltAo2K5NFCybVuLqcOjwmKYPxx4ogJXB92PC4lOSHCmlQRGC8Ah.rjx9sZNoIU.Dc0FXYThfcCGIPWQTeL8eRaHJFbbr8A7RML6LQLHEVui4gibaIXsXtsGfFZrrJN7UOP1SK_l6HVa9EnoUf85ttokNrbGUljaDMLP49BKooZRDINd3.Isq_6wAVwG66gtcya1rbgP6Gv47evYF5IhSKm4wJxBBPphVPWwDs8RSdlPKDnHKP80jwdgSQFr8f_NL1Us_vNpBGYVlLPWxJvyCvc4e7fbH64XHIECh1qyL.NLfrHyRkII8qBFiZW4w51VZjra1FwSuS8xSw_nnvSNkABfntE434KHRg33V6n_u_ZR8YQJlSvooK7SCz8Nij6j508K35OWpb3C"};var cpo = document.createElement('script');cpo.src = '/cdn-cgi/challenge-platform/h/g/orchestrate/chl_page/v1?ray=9137e879694afd3f';window._cf_chl_opt.cOgUHash = location.hash === '' && location.href.indexOf('#') !== -1 ? '#' : location.hash;window._cf_chl_opt.cOgUQuery = location.search === '' && location.href.slice(0, location.href.length - window._cf_chl_opt.cOgUHash.length).indexOf('?') !== -1 ? '?' : location.search;if (window.history && window.history.replaceState) {var ogU = location.pathname + window._cf_chl_opt.cOgUQuery + window._cf_chl_opt.cOgUHash;history.replaceState(null, null, "\/doi\/10.1021\/acs.jmedchem.5b00698?__cf_chl_rt_tk=Cs1_oTAFogPfCMxJLOxkP9gzY6m8XbsRdCrzNQb4D9E-1739817650-1.0.1.1-FyzdGxGGsBKsUlYjwEKHCN0WYSt2Vt3YXPFxy.64FIY" + window._cf_chl_opt.cOgUHash);cpo.onload = function() {history.replaceState(null, null, ogU);}}document.getElementsByTagName('head')[0].appendChild(cpo);}());</script></body></html>