Cyclam Derivatives with a Bis(phosphinate) or a
Phosphinato-Phosphonate Pendant Arm: Ligands for Fast and
Efficient Copper(II) Complexation for Nuclear Medical
Applications

J 2015

Cyclam Derivatives with a Bis(phosphinate) or a Phosphinato-Phosphonate Pendant Arm: Ligands for Fast and Efficient Copper(II) Complexation for Nuclear Medical Applications

DAVID, Tomáš, Vojtěch KUBICEK, Ondrej GUTTEN, Přemysl LUBAL, Jan KOTEK et. al.

Basic information

Original name

Cyclam Derivatives with a Bis(phosphinate) or a Phosphinato-Phosphonate Pendant Arm: Ligands for Fast and Efficient Copper(II) Complexation for Nuclear Medical Applications

Authors

DAVID, Tomáš (203 Czech Republic), Vojtěch KUBICEK (203 Czech Republic), Ondrej GUTTEN (703 Slovakia), Přemysl LUBAL (203 Czech Republic, belonging to the institution), Jan KOTEK (203 Czech Republic), HJ PIETZSCH (276 Germany), Lubomír RULÍŠEK (203 Czech Republic) and Petr HERMANN (203 Czech Republic)

Edition

Inorganic Chemistry, WASHINGTON, American Chemical Society, 2015, 0020-1669

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10402 Inorganic and nuclear chemistry

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.820

RIV identification code

RIV/00216224:14310/15:00081663

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1021/acs.inorgchem.5b01791

UT WoS

000367118100020

Keywords in English

MACROCYCLIC CHELATORS; POSITRON-EMISSION-TOMOGRAPHY; COORDINATION PROPERTIES; METAL-IONS; BIFUNCTIONAL CHELATOR

Abstract

V originále

Cyclam derivatives bearing one geminal bis(phosphinic acid), (H2L1), or phosphinic-phosphonic acid, (H3L2), pendant arm were synthesized and studied as potential copper(II) chelators for nuclear medical applications. The ligands showed good selectivity for copper(II) over zinc(II) and nickel(II) ions. Kinetic study revealed an unusual threestep complex formation mechanism. The initial equilibrium step leads to out-of-cage complexes with Cu2+ bound by the phosphorus-containing pendant arm. These species quickly rearrange to an in-cage complex with cyclam conformation II, which isomerizes to another in-cage complex with cyclam conformation I. The first in-cage complex is quantitatively formed in seconds (pH approximate to 5, 25 degrees C, Cu:L = 1:1, c(M) approximate to 1 mM). At pH >12, I isomers undergo nitrogen atom inversion, leading to III isomers; the structure of the III-[Cu(HL2)] complex in the solid state was confirmed by X-ray diffraction analysis. In an alkaline solution, interconversion of the I and III isomers is mutual, leading to the same equilibrium isomeric mixture; such behavior has been observed here for the first time for copper(II) complexes of cyclam derivatives. Quantum-chemical calculations showed small energetic differences between the isomeric complexes of H3L2 compared with analogous data for isomeric complexes of cyclam derivatives with one or two methylphosphonic acid pendant arm(s). Acid-assisted dissociation proved the kinetic inertness of the complexes. Preliminary radiolabeling of H2L1 and H3L2 with Cu-64 was fast and efficient, even at room temperature. The rare combination of simple ligand synthesis, very fast copper(II) complex formation, high thermodynamic stability, kinetic inertness, efficient radiolabeling, and expected low bone tissue affinity makes such ligands suitably predisposed to serve as chelators of copper radioisotopes in nuclear medicine.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

GA13-08336S, research and development project

Name: Hybridní materiály založené na makrocyklických ligandech pro využití v medicíně

Investor: Czech Science Foundation

Citovat

DAVID, Tomáš, Vojtěch KUBICEK, Ondrej GUTTEN, Přemysl LUBAL, Jan KOTEK, HJ PIETZSCH, Lubomír RULÍŠEK and Petr HERMANN. Cyclam Derivatives with a Bis(phosphinate) or a Phosphinato-Phosphonate Pendant Arm: Ligands for Fast and Efficient Copper(II) Complexation for Nuclear Medical Applications. Inorganic Chemistry. WASHINGTON: American Chemical Society, 2015, vol. 54, No 24, p. 11751-11766. ISSN 0020-1669. Available from: https://dx.doi.org/10.1021/acs.inorgchem.5b01791.

@article{1340369,
   author = {David, Tomáš and Kubicek, Vojtěch and Gutten, Ondrej and Lubal, Přemysl and Kotek, Jan and Pietzsch, HJ and Rulíšek, Lubomír and Hermann, Petr},
   article_location = {WASHINGTON},
   article_number = {24},
   doi = {http://dx.doi.org/10.1021/acs.inorgchem.5b01791},
   keywords = {MACROCYCLIC CHELATORS; POSITRON-EMISSION-TOMOGRAPHY; COORDINATION PROPERTIES; METAL-IONS; BIFUNCTIONAL CHELATOR},
   language = {eng},
   issn = {0020-1669},
   journal = {Inorganic Chemistry},
   title = {Cyclam Derivatives with a Bis(phosphinate) or a Phosphinato-Phosphonate Pendant Arm: Ligands for Fast and Efficient Copper(II) Complexation for Nuclear Medical Applications},
   url = {http://pubs.acs.org/doi/full/10.1021/acs.inorgchem.5b01791},
   volume = {54},
   year = {2015}
}

TY  - JOUR
ID  - 1340369
AU  - David, Tomáš - Kubicek, Vojtěch - Gutten, Ondrej - Lubal, Přemysl - Kotek, Jan - Pietzsch, HJ - Rulíšek, Lubomír - Hermann, Petr
PY  - 2015
TI  - Cyclam Derivatives with a Bis(phosphinate) or a Phosphinato-Phosphonate Pendant Arm: Ligands for Fast and Efficient Copper(II) Complexation for Nuclear Medical Applications
JF  - Inorganic Chemistry
VL  - 54
IS  - 24
SP  - 11751-11766
EP  - 11751-11766
PB  - American Chemical Society
SN  - 00201669
KW  - MACROCYCLIC CHELATORS
KW  - POSITRON-EMISSION-TOMOGRAPHY
KW  - COORDINATION PROPERTIES
KW  - METAL-IONS
KW  - BIFUNCTIONAL CHELATOR
UR  - http://pubs.acs.org/doi/full/10.1021/acs.inorgchem.5b01791
N2  - Cyclam derivatives bearing one geminal bis(phosphinic acid), (H2L1), or phosphinic-phosphonic acid, (H3L2), pendant arm were synthesized and studied as potential copper(II) chelators for nuclear medical applications. The ligands showed good selectivity for copper(II) over zinc(II) and nickel(II) ions. Kinetic study revealed an unusual threestep complex formation mechanism. The initial equilibrium step leads to out-of-cage complexes with Cu2+ bound by the phosphorus-containing pendant arm. These species quickly rearrange to an in-cage complex with cyclam conformation II, which isomerizes to another in-cage complex with cyclam conformation I. The first in-cage complex is quantitatively formed in seconds (pH approximate to 5, 25 degrees C, Cu:L = 1:1, c(M) approximate to 1 mM). At pH >12, I isomers undergo nitrogen atom inversion, leading to III isomers; the structure of the III-[Cu(HL2)] complex in the solid state was confirmed by X-ray diffraction analysis. In an alkaline solution, interconversion of the I and III isomers is mutual, leading to the same equilibrium isomeric mixture; such behavior has been observed here for the first time for copper(II) complexes of cyclam derivatives. Quantum-chemical calculations showed small energetic differences between the isomeric complexes of H3L2 compared with analogous data for isomeric complexes of cyclam derivatives with one or two methylphosphonic acid pendant arm(s). Acid-assisted dissociation proved the kinetic inertness of the complexes. Preliminary radiolabeling of H2L1 and H3L2 with Cu-64 was fast and efficient, even at room temperature. The rare combination of simple ligand synthesis, very fast copper(II) complex formation, high thermodynamic stability, kinetic inertness, efficient radiolabeling, and expected low bone tissue affinity makes such ligands suitably predisposed to serve as chelators of copper radioisotopes in nuclear medicine.
ER  -

DAVID, Tomáš, Vojtěch KUBICEK, Ondrej GUTTEN, Přemysl LUBAL, Jan KOTEK, HJ PIETZSCH, Lubomír RULÍŠEK and Petr HERMANN. Cyclam Derivatives with a Bis(phosphinate) or a Phosphinato-Phosphonate Pendant Arm: Ligands for Fast and Efficient Copper(II) Complexation for Nuclear Medical Applications. \textit{Inorganic Chemistry}. WASHINGTON: American Chemical Society, 2015, vol.~54, No~24, p.~11751-11766. ISSN~0020-1669. Available from: https://dx.doi.org/10.1021/acs.inorgchem.5b01791.

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