Tracking the multiple-step formation of an iron(Ⅲ) complex and its application in photodynamic therapy for breast cancer
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摘要
A tandem reaction of pyridin-2-ylmethanamine(L1′) with 8-hydroxyquinoline-2-carbaldehyde(HL1) assisted by FeCl_3 was observed to give the new nitrogen heterocycle HL3(HL3=2-(imidazo[1,5-a]pyridin-3-yl)quinolin-8-ol) as its Fe(Ⅲ) complex,[Fe(L3)Cl_2](Fe1). Electrospray ionization mass spectrometry(ESI-MS) reveals its formation involves three steps:(1) coordination of both HL1 and L1′ to Fe,(2) aldehyde-amine coupling, and(3) ring closure. The results of electronic absorption spectroscopy, cyclic voltammetry, and density functional theory(DFT) calculations show the proximity of the optical transition energy to that of the excitation of ~3O_2 to ~1O_2, which prompted us to explore its application as a photosensitizer for photodynamic therapy(PDT). Photo-toxicity studies show that Fe1 exhibits the highest anti-proliferation efficiency in human breast cancer MDA-MB-231 cells under light irradiation. Moreover, studies with orthotopic models of breast cancer further expounded the anti-tumor activity of Fe1 with no significant toxicity to other organs and low retention in the body.
A tandem reaction of pyridin-2-ylmethanamine(L1′) with 8-hydroxyquinoline-2-carbaldehyde(HL1) assisted by FeCl_3 was observed to give the new nitrogen heterocycle HL3(HL3=2-(imidazo[1,5-a]pyridin-3-yl)quinolin-8-ol) as its Fe(Ⅲ) complex,[Fe(L3)Cl_2](Fe1). Electrospray ionization mass spectrometry(ESI-MS) reveals its formation involves three steps:(1) coordination of both HL1 and L1′ to Fe,(2) aldehyde-amine coupling, and(3) ring closure. The results of electronic absorption spectroscopy, cyclic voltammetry, and density functional theory(DFT) calculations show the proximity of the optical transition energy to that of the excitation of ~3O_2 to ~1O_2, which prompted us to explore its application as a photosensitizer for photodynamic therapy(PDT). Photo-toxicity studies show that Fe1 exhibits the highest anti-proliferation efficiency in human breast cancer MDA-MB-231 cells under light irradiation. Moreover, studies with orthotopic models of breast cancer further expounded the anti-tumor activity of Fe1 with no significant toxicity to other organs and low retention in the body.
A tandem reaction of pyridin-2-ylmethanamine(L1′) with 8-hydroxyquinoline-2-carbaldehyde(HL1) assisted by FeCl_3 was observed to give the new nitrogen heterocycle HL3(HL3=2-(imidazo[1,5-a]pyridin-3-yl)quinolin-8-ol) as its Fe(Ⅲ) complex,[Fe(L3)Cl_2](Fe1). Electrospray ionization mass spectrometry(ESI-MS) reveals its formation involves three steps:(1) coordination of both HL1 and L1′ to Fe,(2) aldehyde-amine coupling, and(3) ring closure. The results of electronic absorption spectroscopy, cyclic voltammetry, and density functional theory(DFT) calculations show the proximity of the optical transition energy to that of the excitation of ~3O_2 to ~1O_2, which prompted us to explore its application as a photosensitizer for photodynamic therapy(PDT). Photo-toxicity studies show that Fe1 exhibits the highest anti-proliferation efficiency in human breast cancer MDA-MB-231 cells under light irradiation. Moreover, studies with orthotopic models of breast cancer further expounded the anti-tumor activity of Fe1 with no significant toxicity to other organs and low retention in the body.
引文
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3 Zeng MH,Yin Z,Liu ZH,Xu HB,Feng YC,Hu YQ,Chang LX,Zhang YX,Huang J,Kurmoo M.Angew Chem Int Ed,2016,55:11407-11411
4 Schr?der D.Acc Chem Res,2012,45:1521-1532
5 Chen XM,Tong ML.Acc Chem Res,2007,40:162-170
6(a)Zhong JP,Liu B,Yang T,Liu YJ,Zhu ZH,Shi BF,Kurmoo M,Zeng MH.Inorg Chem,2017,56:10123-10126;(b)Chen Q,Zeng MH,Zhou YL,Zou HH,Kurmoo M.Chem Mater,2010,22:2114-2119
7 Chen Y,Li L,Chen Z,Liu Y,Hu H,Chen W,Liu W,Li Y,Lei T,Cao Y,Kang Z,Lin M,Li W.Inorg Chem,2012,51:9705-9713
8 Brown CJ,Toste FD,Bergman RG,Raymond KN.Chem Rev,2015,115:3012-3035
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10 Yang Y,Zhao Q,Feng W,Li F.Chem Rev,2013,113:192-270
11 Liu W,Gust R.Coord Chem Rev,2016,329:191-213
12(a)Park GY,Wilson JJ,Song Y,Lippard SJ.Proc Natl Acad Sci USA,2012,109:11987-11992;(b)Bruno PM,Liu Y,Park GY,Murai J,Koch CE,Eisen TJ,Pritchard JR,Pommier Y,Lippard SJ,Hemann MT.Nat Med,2017,23:461-471
13 Huang H,Yu B,Zhang P,Huang J,Chen Y,Gasser G,Ji L,Chao H.Angew Chem Int Ed,2015,54:14049-14052
14(a)Felsher DW.Nat Rev Cancer,2003,3:180-187;(b)Zheng Z,Zhang T,Liu H,Chen Y,Kwok RTK,Ma C,Zhang P,Sung HHY,Williams ID,Lam JWY,Wong KS,Tang BZ.ACS Nano,2018,12:8145-8159
15 Heinemann F,Karges J,Gasser G.Acc Chem Res,2017,50:2727-2736
16(a)Sgambellone MA,David A,Garner RN,Dunbar KR,Turro C.JAm Chem Soc,2013,135:11274-11282;(b)Majumdar P,Yuan X,Li S,Le Guennic B,Ma J,Zhang C,Jacquemin D,Zhao J.J Mater Chem B,2014,2:2838-2854;(c)?hrstr?m L.Nat Chem,2018,10:372
17 Basu U,Khan I,Hussain A,Kondaiah P,Chakravarty AR.Angew Chem Int Ed,2012,51:2658-2661
18 Sheldrick GM.Acta Crystallogr Sect C:Struct Chem,2015,71:3-8
19 Lu K,He C,Lin W.J Am Chem Soc,2015,137:7600-7603
20(a)Liu F,Du J,Song D,Xu M,Sun G.Chem Commun,2016,52:4636-4639;(b)Chen H,Tian J,He W,Guo Z.J Am Chem Soc,2015,137:1539-1547
21 Frisch MJ,Trucks GW,Schlegel HB,et al.Gaussian 16,Revision A.03.Wallingford CT:Gaussian,Inc.,2016
22 Nam JS,Kang MG,Kang J,Park SY,Lee SJC,Kim HT,Seo JK,Kwon OH,Lim MH,Rhee HW,Kwon TH.J Am Chem Soc,2016,138:10968-10977
23 Huang L,Li Z,Zhao Y,Zhang Y,Wu S,Zhao J,Han G.J Am Chem Soc,2016,138:14586-14591
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