Comba Peter, Kubeil Manja, Pietzsch Jens, Rudolf Henning, Stephan Holger, Zarschler Kristof
Anorganisch-Chemisches Institut, Universität Heidelberg , INF 270, D-69120 Heidelberg, Germany.
Inorg Chem. 2014 Jul 7;53(13):6698-707. doi: 10.1021/ic500476u. Epub 2014 Jun 6.
The three new dioxo-tetraazamacrocyclic ligands with a fused, very rigid bispidine (3,7-diazabicyclo[3.3.1]nonane) group connecting the two tertiary amine donors, and ethyl, propyl, or benzene groups connecting the two amide donors are highly preorganized and lead to very stable, uncharged Cu(II) complexes. Solution spectroscopy and solid state structures indicate that these are square pyramidal with a solvent molecule occupying the apical position. Cyclic voltammetry defines a reversible Cu(III/II) couple and a strongly negative irreversible Cu(II/I) couple (ca. -2 V vs Fc/Fc(+)), indicating that the Cu(II) complexes are very stable in solution. This is supported by superoxide dismutase (SOD) and human serum challenge experiments as well as the biodistribution, which all show that the benzene-based ligand has the highest in vitro and in vivo stability and that this was expected on the basis of the macrocycle ring size and shape and the highest degree of preorganization. This ligand is easy to functionalize for a possible coupling to biological vector molecules and/or fluorescence markers for PET (positron emission tomography) and multimodal imaging (i.e., PET and optical imaging).
三种新型二氧代四氮杂大环配体，带有一个稠合的、非常刚性的双吡啶（3,7-二氮杂双环[3.3.1]壬烷）基团连接两个叔胺供体，以及乙基、丙基或苯基团连接两个酰胺供体，它们高度预组织化，能形成非常稳定的、不带电荷的Cu(II)配合物。溶液光谱和固态结构表明，这些配合物为四方锥构型，有一个溶剂分子占据顶端位置。循环伏安法确定了一个可逆的Cu(III/II)电对和一个强烈负向的不可逆Cu(II/I)电对（相对于Fc/Fc(+)约为 -2 V），这表明Cu(II)配合物在溶液中非常稳定。超氧化物歧化酶（SOD）和人血清挑战实验以及生物分布情况均支持这一点，所有这些都表明基于苯的配体具有最高的体外和体内稳定性，并且基于大环的环大小和形状以及最高程度的预组织化，这是预期的结果。这种配体易于功能化，以便可能与生物载体分子和/或用于正电子发射断层扫描（PET）和多模态成像（即PET和光学成像）的荧光标记物偶联。
