From Symmetrical to Asymmetrical Nitrido Phosphino-thiol Complexes: A New Class of Neutral Mixed-Ligand 99mTc Compounds as Potential Brain Imaging Agents
详细信息 查看全文
- 作者：Cristina Bolzati ; Elisa Benini ; Mario Cavazza-Ceccato ; Emiliano Cazzola ; Erica Malagò ; Stefania Agostini ; Francesco Tisato ; Fiorenzo Refosco ; and Giuliano Bandoli
- 刊名：Bioconjugate Chemistry
- 出版年：2006
- 出版时间：March 2006
- 年：2006
- 卷：17
- 期：2
- 页码：419 - 428
- 全文大小：236K
- 年卷期：v.17,no.2(March 2006)
- ISSN：1520-4812
文摘
A general procedure is presented for the preparation of a new class of nitrido asymmetrical Tc-99m complexescontaining two different bidentate ligands bound to the same [Tc(N)]2+ core that could be used to design eitheressential or target specific imaging agents. This procedure is based on the chemical properties of a newmonosubstituted [Tc(N)(R2PS)Cl(PPh3)] species composed of a Tc
N multiple bond and an ancillary phosphinethiol ligand (R2PSH). This intermediate readily reacts with bidentate mononegative ligands (S
Y) containing soft
-donor coordinating atoms to give neutral pentacoordinate asymmetrical complexes of the type [Tc(N)(R2PS)(SY)]. The ability of several bidentate ligands containing different combination of heteroatoms (S, N, O) toform complexes with the [Tc(N)(R2PS)]+ building block was investigated. It was found that mononegativedithiocarbamate (DTC) or cysteine carboxyl derivate ligands promptly react with the monosubstituted species toform the final mixed compound in high yield. Preliminary biodistribution data in rats of some representative[Tc(N)(R2PS)(DTC)] compounds revealed an interesting initial brain uptake (in the range 0.20 ± 0.01% ID/g and0.91 ± 0.06% ID/g), indicating their ability to cross in and out of the intact BBB. In these complexes thedithiocarbamate, or more generally the bidentate ligand (SY), can be designed to carry a functional group or abioactive molecule, which could be involved in a trapping mechanism to increase brain retention for longer timeintervals. These results could be conveniently utilized to devise a new procedure for the production of a novelclass of brain perfusion and/or brain receptor imaging agents.
N multiple bond and an ancillary phosphinethiol ligand (R2PSH). This intermediate readily reacts with bidentate mononegative ligands (SY) containing soft-donor coordinating atoms to give neutral pentacoordinate asymmetrical complexes of the type [Tc(N)(R2PS)(SY)]. The ability of several bidentate ligands containing different combination of heteroatoms (S, N, O) toform complexes with the [Tc(N)(R2PS)]+ building block was investigated. It was found that mononegativedithiocarbamate (DTC) or cysteine carboxyl derivate ligands promptly react with the monosubstituted species toform the final mixed compound in high yield. Preliminary biodistribution data in rats of some representative[Tc(N)(R2PS)(DTC)] compounds revealed an interesting initial brain uptake (in the range 0.20 ± 0.01% ID/g and0.91 ± 0.06% ID/g), indicating their ability to cross in and out of the intact BBB. In these complexes thedithiocarbamate, or more generally the bidentate ligand (SY), can be designed to carry a functional group or abioactive molecule, which could be involved in a trapping mechanism to increase brain retention for longer timeintervals. These results could be conveniently utilized to devise a new procedure for the production of a novelclass of brain perfusion and/or brain receptor imaging agents.