Synthesis of novel 1,3,5-cis,cis-triaminocyclohexane ligand based Cu(II) complexes as potential radiopharmaceuticals and correlation of structure and serum stability

Gyungse Park, Ekaterina Dadachova, Ann Przyborowska, Su jen Lai, Dangshe Ma, Grant Broker, Robin D. Rogers, Roy P. Planalp, Martin W. Brechbiel

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The present study describes the synthesis of Cu(II) and radioactive 67.64Cu(II) complexes with N,N′,N″-tris(2-pyridylmethyl)-1,3,5-cis,cis-triaminocyclohexane (tachpyr) and a new pyridyl ring alkylated derivative, N,N′,N″-tris (6-methyl-2-pyridylmethyl)-1,3,5-cis,cis-triaminocyclohexane (tach-6-Me-pyr) and the investigation of their structural and solution properties as well as stability in human serum. Facile formation of both the 'cold' and 67,64Cu-radiolabeled complexes, [Cu(tachpyr)]2+ and [Cu(tach-6-Me-pyr)]2+, occurs in aqueous (0.15 M NH4OAc buffer, pH 6.5) or methanolic solvent. X-ray crystallography reveals that Cu(II) is hexacoordinate in [Cu(tachpyr)]2+ while methylation at the 6-position of the pyridyl donors in tachpyr produces considerable steric hindrance. Thus one pyridyl arm of tach-6-Mepyr is rotated entirely away from copper in [Cu(tach-6-Mepyr)]2+, resulting in a highly distorted trigonal-bipyramidal coordination geometry. The solid-state structures of the complexes correlate well with their stabilities in human serum at 37 °C. Thus, [67Cu(tachpyr)]2+ possesses excellent stability, being unchanged after a period of 7 days, while [67Cu(tach-6-Mepyr)]2+ decomposes within 1 h. Tachpyr may be an excellent candidate for developing new Cu(II) radiopharmaceuticals for diagnosis and therapy.

Original languageEnglish (US)
Pages (from-to)3155-3163
Number of pages9
JournalPolyhedron
Volume20
Issue number26-27
DOIs
StatePublished - Dec 1 2001
Externally publishedYes

Fingerprint

Radiopharmaceuticals
serums
Ligands
ligands
synthesis
Serum
methylation
Methylation
X ray crystallography
crystallography
therapy
buffers
Derivatives
solid state
Copper
copper
Geometry
rings
X Ray Crystallography
geometry

Keywords

  • Crystal structures
  • Cu(II) complexes
  • Radiopharmaceuticals
  • Serum stability
  • Structure-activity relationship

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry
  • Physical and Theoretical Chemistry
  • Materials Chemistry

Cite this

Synthesis of novel 1,3,5-cis,cis-triaminocyclohexane ligand based Cu(II) complexes as potential radiopharmaceuticals and correlation of structure and serum stability. / Park, Gyungse; Dadachova, Ekaterina; Przyborowska, Ann; Lai, Su jen; Ma, Dangshe; Broker, Grant; Rogers, Robin D.; Planalp, Roy P.; Brechbiel, Martin W.

In: Polyhedron, Vol. 20, No. 26-27, 01.12.2001, p. 3155-3163.

Research output: Contribution to journalArticle

Park, G, Dadachova, E, Przyborowska, A, Lai, SJ, Ma, D, Broker, G, Rogers, RD, Planalp, RP & Brechbiel, MW 2001, 'Synthesis of novel 1,3,5-cis,cis-triaminocyclohexane ligand based Cu(II) complexes as potential radiopharmaceuticals and correlation of structure and serum stability', Polyhedron, vol. 20, no. 26-27, pp. 3155-3163. https://doi.org/10.1016/S0277-5387(01)00927-5
Park, Gyungse ; Dadachova, Ekaterina ; Przyborowska, Ann ; Lai, Su jen ; Ma, Dangshe ; Broker, Grant ; Rogers, Robin D. ; Planalp, Roy P. ; Brechbiel, Martin W. / Synthesis of novel 1,3,5-cis,cis-triaminocyclohexane ligand based Cu(II) complexes as potential radiopharmaceuticals and correlation of structure and serum stability. In: Polyhedron. 2001 ; Vol. 20, No. 26-27. pp. 3155-3163.
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abstract = "The present study describes the synthesis of Cu(II) and radioactive 67.64Cu(II) complexes with N,N′,N″-tris(2-pyridylmethyl)-1,3,5-cis,cis-triaminocyclohexane (tachpyr) and a new pyridyl ring alkylated derivative, N,N′,N″-tris (6-methyl-2-pyridylmethyl)-1,3,5-cis,cis-triaminocyclohexane (tach-6-Me-pyr) and the investigation of their structural and solution properties as well as stability in human serum. Facile formation of both the 'cold' and 67,64Cu-radiolabeled complexes, [Cu(tachpyr)]2+ and [Cu(tach-6-Me-pyr)]2+, occurs in aqueous (0.15 M NH4OAc buffer, pH 6.5) or methanolic solvent. X-ray crystallography reveals that Cu(II) is hexacoordinate in [Cu(tachpyr)]2+ while methylation at the 6-position of the pyridyl donors in tachpyr produces considerable steric hindrance. Thus one pyridyl arm of tach-6-Mepyr is rotated entirely away from copper in [Cu(tach-6-Mepyr)]2+, resulting in a highly distorted trigonal-bipyramidal coordination geometry. The solid-state structures of the complexes correlate well with their stabilities in human serum at 37 °C. Thus, [67Cu(tachpyr)]2+ possesses excellent stability, being unchanged after a period of 7 days, while [67Cu(tach-6-Mepyr)]2+ decomposes within 1 h. Tachpyr may be an excellent candidate for developing new Cu(II) radiopharmaceuticals for diagnosis and therapy.",
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T1 - Synthesis of novel 1,3,5-cis,cis-triaminocyclohexane ligand based Cu(II) complexes as potential radiopharmaceuticals and correlation of structure and serum stability

AU - Park, Gyungse

AU - Dadachova, Ekaterina

AU - Przyborowska, Ann

AU - Lai, Su jen

AU - Ma, Dangshe

AU - Broker, Grant

AU - Rogers, Robin D.

AU - Planalp, Roy P.

AU - Brechbiel, Martin W.

PY - 2001/12/1

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N2 - The present study describes the synthesis of Cu(II) and radioactive 67.64Cu(II) complexes with N,N′,N″-tris(2-pyridylmethyl)-1,3,5-cis,cis-triaminocyclohexane (tachpyr) and a new pyridyl ring alkylated derivative, N,N′,N″-tris (6-methyl-2-pyridylmethyl)-1,3,5-cis,cis-triaminocyclohexane (tach-6-Me-pyr) and the investigation of their structural and solution properties as well as stability in human serum. Facile formation of both the 'cold' and 67,64Cu-radiolabeled complexes, [Cu(tachpyr)]2+ and [Cu(tach-6-Me-pyr)]2+, occurs in aqueous (0.15 M NH4OAc buffer, pH 6.5) or methanolic solvent. X-ray crystallography reveals that Cu(II) is hexacoordinate in [Cu(tachpyr)]2+ while methylation at the 6-position of the pyridyl donors in tachpyr produces considerable steric hindrance. Thus one pyridyl arm of tach-6-Mepyr is rotated entirely away from copper in [Cu(tach-6-Mepyr)]2+, resulting in a highly distorted trigonal-bipyramidal coordination geometry. The solid-state structures of the complexes correlate well with their stabilities in human serum at 37 °C. Thus, [67Cu(tachpyr)]2+ possesses excellent stability, being unchanged after a period of 7 days, while [67Cu(tach-6-Mepyr)]2+ decomposes within 1 h. Tachpyr may be an excellent candidate for developing new Cu(II) radiopharmaceuticals for diagnosis and therapy.

AB - The present study describes the synthesis of Cu(II) and radioactive 67.64Cu(II) complexes with N,N′,N″-tris(2-pyridylmethyl)-1,3,5-cis,cis-triaminocyclohexane (tachpyr) and a new pyridyl ring alkylated derivative, N,N′,N″-tris (6-methyl-2-pyridylmethyl)-1,3,5-cis,cis-triaminocyclohexane (tach-6-Me-pyr) and the investigation of their structural and solution properties as well as stability in human serum. Facile formation of both the 'cold' and 67,64Cu-radiolabeled complexes, [Cu(tachpyr)]2+ and [Cu(tach-6-Me-pyr)]2+, occurs in aqueous (0.15 M NH4OAc buffer, pH 6.5) or methanolic solvent. X-ray crystallography reveals that Cu(II) is hexacoordinate in [Cu(tachpyr)]2+ while methylation at the 6-position of the pyridyl donors in tachpyr produces considerable steric hindrance. Thus one pyridyl arm of tach-6-Mepyr is rotated entirely away from copper in [Cu(tach-6-Mepyr)]2+, resulting in a highly distorted trigonal-bipyramidal coordination geometry. The solid-state structures of the complexes correlate well with their stabilities in human serum at 37 °C. Thus, [67Cu(tachpyr)]2+ possesses excellent stability, being unchanged after a period of 7 days, while [67Cu(tach-6-Mepyr)]2+ decomposes within 1 h. Tachpyr may be an excellent candidate for developing new Cu(II) radiopharmaceuticals for diagnosis and therapy.

KW - Crystal structures

KW - Cu(II) complexes

KW - Radiopharmaceuticals

KW - Serum stability

KW - Structure-activity relationship

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