Cowley Andrew R, Dilworth Jonathan R, Donnelly Paul S, Heslop Julia M, Ratcliffe Steven J
Chemical Crystallography Laboratory, University of Oxford, 12 Mansfield Road, Oxford, UK OX1 3TA.
Dalton Trans. 2007 Jan 14(2):209-17. doi: 10.1039/b612142j. Epub 2006 Nov 14.
Two new bifunctional chelators that are derivatives of the bis(thiosemicarbazone) ATSMH(2) proligand have been prepared, one with two phenyl carboxylate substituents on the exocyclic nitrogens (L(1)H(2)) and one with a single phenyl carboxylate (L(2)H(2)). The new ligands have been characterised by NMR spectroscopy, mass spectrometry and in the case of L(1)H(2) by X-ray crystallography. The copper, nickel and zinc complexes of the new ligands have been synthesised and characterised. Electrochemical measurements show that the copper(II) complexes undergo a reversible reduction attributable to a Cu(II)/Cu(I) process. The new proligands have been tethered to the N-alpha-Boc-protected amino acids lysine and ornithine using solution and solid phase methods. The new amino acid conjugates form copper complexes and the complexes have been characterised by mass spectrometry and electronic spectroscopy. The bifunctional chelator L(2)H(2) has been conjugated to the tumour targeting peptide octreotide and the new ATSMH(2)-octreotide conjugate and its copper complex have been characterized by mass spectrometry. These new systems have the potential to be used for new targeted copper radiopharmaceuticals for imaging and therapy.
已经制备了两种新的双功能螯合剂，它们是双（硫代半卡巴腙）ATSMH(2)前体配体的衍生物，一种在外环氮上带有两个苯基羧酸盐取代基（L(1)H(2)），另一种带有单个苯基羧酸盐（L(2)H(2)）。这些新配体已通过核磁共振光谱、质谱进行了表征，对于L(1)H(2)还通过X射线晶体学进行了表征。合成并表征了新配体的铜、镍和锌配合物。电化学测量表明，铜（II）配合物经历了归因于Cu（II）/Cu（I）过程的可逆还原。使用溶液法和固相法将新的前体配体与N-α-叔丁氧羰基保护的氨基酸赖氨酸和鸟氨酸连接。新的氨基酸缀合物形成铜配合物，并且通过质谱和电子光谱对配合物进行了表征。双功能螯合剂L(2)H(2)已与肿瘤靶向肽奥曲肽缀合，并且通过质谱对新的ATSMH(2)-奥曲肽缀合物及其铜配合物进行了表征。这些新系统有潜力用于新型靶向铜放射性药物的成像和治疗。
