公开(公告)号：US09944668B2

公开(公告)日：2018-04-17

申请号：US14759114

申请日：2014-01-07

申请人： Peter Caravan ,  Eric M. Gale ,  Galen S. Loving ,  Shereya Mukherjee ,  Jiang Zhu

发明人： Peter Caravan ,  Eric M. Gale ,  Galen S. Loving ,  Shereya Mukherjee ,  Jiang Zhu

IPC分类号： A61K49/14 ,  A61K49/16 ,  C07F13/00 ,  A61K49/06 ,  A61K51/04 ,  A61K49/10 ,  A61B5/055 ,  A61B5/00

CPC分类号： C07F13/005 ,  A61B5/0035 ,  A61B5/055 ,  A61K49/06 ,  A61K49/103 ,  A61K49/106 ,  A61K49/14 ,  A61K49/16 ,  A61K51/04 ,  A61K51/0455

摘要： Manganese coordination complexes with utility as magnetic resonance probes and as biological reductant sensors are disclosed. In one embodiment, ligands can stabilize both the Mn2+ and Mn3+ oxidation states. In the presence of a reductant such as glutathione, low relaxivity MnIII-HBET is rapidly converted to high relaxivity MnII-HBET with a 3-fold increase in relaxivity, and concomitant increase in magnetic resonance signal. In another embodiment, ligands were designed to chelate Mn(ll) in a thermodynamically stable and kinetically inert fashion while allowing for direct interaction of Mn(ll) with water. In yet another embodiment, high molecular weight multimers containing six Mn(ll) chelators were prepared. The high molecular weight results in slower tumbling of the molecules in solution and can strongly enhance the Mn(ll) relaxivity.

公开(公告)号：US20150336997A1

公开(公告)日：2015-11-26

申请号：US14759114

申请日：2014-01-07

申请人： Peter CARAVAN ,  Eirc M. GALE ,  Galen S. LOVING ,  Shereya MUKHERJEE ,  Jiang ZHU

发明人： Peter Caravan ,  Eric M. Gale ,  Galen S. Loving ,  Shereya Mukherjee ,  Jiang Zhu

IPC分类号： C07F13/00 ,  A61B5/00 ,  A61B5/055 ,  A61K51/04 ,  A61K49/10

CPC分类号： C07F13/005 ,  A61B5/0035 ,  A61B5/055 ,  A61K49/06 ,  A61K49/103 ,  A61K49/106 ,  A61K49/14 ,  A61K49/16 ,  A61K51/04 ,  A61K51/0455

摘要： Manganese coordination complexes with utility as magnetic resonance probes and as biological reductant sensors are disclosed. In one embodiment, ligands can stabilize both the Mn2+ and Mn3+ oxidation states. In the presence of a reductant such as glutathione, low relaxivity MnIII-HBET is rapidly converted to high relaxivity MnII-HBET with a 3-fold increase in relaxivity, and concomitant increase in magnetic resonance signal. In another embodiment, ligands were designed to chelate Mn(ll) in a thermodynamically stable and kinetically inert fashion while allowing for direct interaction of Mn(ll) with water. In yet another embodiment, high molecular weight multimers containing six Mn(ll) chelators were prepared. The high molecular weight results in slower tumbling of the molecules in solution and can strongly enhance the Mn(ll) relaxivity.

摘要翻译： 公开了作为磁共振探针和生物还原剂传感器的锰配位络合物。 在一个实施方案中，配体可以稳定Mn 2+和Mn 3+氧化态。 在还原剂如谷胱甘肽的存在下，低弛豫MnIII-HBET快速转化为高弛豫度MnII-HBET，松弛度增加3倍，磁共振信号伴随增加。 在另一个实施方案中，设计配体以热力学稳定和动力学惰性的方式螯合Mn（II），同时允许Mn（II）与水直接相互作用。 在另一个实施方案中，制备含有六个Mn（II）螯合剂的高分子量多聚物。 高分子量导致溶液中分子的翻滚较慢，并且可以强烈增强Mn（II）弛豫度。

公开(公告)号：US20150336996A1

公开(公告)日：2015-11-26

申请号：US14758825

申请日：2014-01-07

申请人： Peter CARAVAN ,  Eric M. GALE ,  Gales S. LOVING ,  Shereya MUKHERJEE ,  Jiang ZHU ,  THE GENERAL HOSPITAL CORPORATION

发明人： Peter Caravan ,  Eric M. Gale ,  Galen S. Loving ,  Shereya Mukherjee ,  Jiang Zhu

IPC分类号： C07F13/00 ,  A61K49/14 ,  A61K49/16 ,  A61K49/06

CPC分类号： C07F13/005 ,  A61B5/0035 ,  A61B5/055 ,  A61K49/06 ,  A61K49/103 ,  A61K49/106 ,  A61K49/14 ,  A61K49/16 ,  A61K51/04 ,  A61K51/0455

摘要： Manganese coordination complexes with utility as magnetic resonance probes and as biological reductant sensors are disclosed. In one embodiment, ligands can stabilize both the Mn2+ and Mn3+ oxidation states. In the presence of a reductant such as glutathione, low relaxivity MnIII-HBET is rapidly converted to high relaxivity MnII-HBET with a 3-fold increase in relaxivity, and concomitant increase in magnetic resonance signal. In another embodiment, ligands were designed to chelate Mn(ll) in a thermodynamically stable and kinetically inert fashion while allowing for direct interaction of Mn(ll) with water. In yet another embodiment, high molecular weight multimers containing six Mn(ll) chelators were prepared. The high molecular weight results in slower tumbling of the molecules in solution and can strongly enhance the Mn(ll) relaxivity.