Inclusion compounds containing a drug

Structure and thermal stability of the first clathrates of nitrazepam and isothiocyanato ethanol complexes of Co(II) and Ni(II)

P. Bombicz, Edit Forizs, J. Madarász, Andrea Deák, A. Kálmán

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38 Citations (Scopus)

Abstract

Syntheses, crystal structures and comparative analytical investigations on the first two inclusion compounds of an antiepileptic drug, nitrazepam (1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one) are reported. The biologically active molecule forms isostructural clathrates with diaquadiethanolbis(isothiocyanato) complexes of both cobalt(II) and nickel(II) in molar ratios of 1:2 [M(NCS)2(C2H5OH)2 (H2O)2]·2C15H11 N3O3 (M = Co2+, 1, and M = Ni2+, 2). Detailed analyses of the structures, the secondary interactions, the neutral drug conformations, the FTIR spectra and thermal stabilities of the clathrates, in comparison with those of the crystalline nitrazepam, have been carried out. In the crystal structures there are only host-guest hydrogen bonds of O···H, N···H and S···H type. Owing to the comparable size of the two constituents neither host-host nor guest-guest secondary interactions occur. In the first thermal decomposition step a parallel release of ethanol and water was observed by simultaneous thermogravimetric and differential thermal analysis measurements. This indicates that some bonds of the metal complex unit and the host-guest secondary interactions in 1 and 2 are weaker than interactions in the pure drug. If an easy release of ethanol and water occurs during dissolution of 1 and 2, it might result in an improved bioavailability of the drug, which is soluble only in aqueous ethanol.

Original languageEnglish
Pages (from-to)229-235
Number of pages7
JournalInorganica Chimica Acta
Volume315
Issue number2
DOIs
Publication statusPublished - Apr 27 2001

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Nitrazepam
clathrates
drugs
Thermodynamic stability
Ethanol
ethyl alcohol
thermal stability
Hot Temperature
inclusions
Crystal structure
Differential Thermal Analysis
Pharmaceutical Preparations
Water
Coordination Complexes
Fourier Transform Infrared Spectroscopy
Metal complexes
Cobalt
Nickel
Drug Interactions
bioavailability

Keywords

  • Cobalt complexes
  • Crystal structures
  • Drug complexes
  • Isothiocyanato complexes
  • Nickel complexes

ASJC Scopus subject areas

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

Cite this

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title = "Inclusion compounds containing a drug: Structure and thermal stability of the first clathrates of nitrazepam and isothiocyanato ethanol complexes of Co(II) and Ni(II)",
abstract = "Syntheses, crystal structures and comparative analytical investigations on the first two inclusion compounds of an antiepileptic drug, nitrazepam (1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one) are reported. The biologically active molecule forms isostructural clathrates with diaquadiethanolbis(isothiocyanato) complexes of both cobalt(II) and nickel(II) in molar ratios of 1:2 [M(NCS)2(C2H5OH)2 (H2O)2]·2C15H11 N3O3 (M = Co2+, 1, and M = Ni2+, 2). Detailed analyses of the structures, the secondary interactions, the neutral drug conformations, the FTIR spectra and thermal stabilities of the clathrates, in comparison with those of the crystalline nitrazepam, have been carried out. In the crystal structures there are only host-guest hydrogen bonds of O···H, N···H and S···H type. Owing to the comparable size of the two constituents neither host-host nor guest-guest secondary interactions occur. In the first thermal decomposition step a parallel release of ethanol and water was observed by simultaneous thermogravimetric and differential thermal analysis measurements. This indicates that some bonds of the metal complex unit and the host-guest secondary interactions in 1 and 2 are weaker than interactions in the pure drug. If an easy release of ethanol and water occurs during dissolution of 1 and 2, it might result in an improved bioavailability of the drug, which is soluble only in aqueous ethanol.",
keywords = "Cobalt complexes, Crystal structures, Drug complexes, Isothiocyanato complexes, Nickel complexes",
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year = "2001",
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T2 - Structure and thermal stability of the first clathrates of nitrazepam and isothiocyanato ethanol complexes of Co(II) and Ni(II)

AU - Bombicz, P.

AU - Forizs, Edit

AU - Madarász, J.

AU - Deák, Andrea

AU - Kálmán, A.

PY - 2001/4/27

Y1 - 2001/4/27

N2 - Syntheses, crystal structures and comparative analytical investigations on the first two inclusion compounds of an antiepileptic drug, nitrazepam (1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one) are reported. The biologically active molecule forms isostructural clathrates with diaquadiethanolbis(isothiocyanato) complexes of both cobalt(II) and nickel(II) in molar ratios of 1:2 [M(NCS)2(C2H5OH)2 (H2O)2]·2C15H11 N3O3 (M = Co2+, 1, and M = Ni2+, 2). Detailed analyses of the structures, the secondary interactions, the neutral drug conformations, the FTIR spectra and thermal stabilities of the clathrates, in comparison with those of the crystalline nitrazepam, have been carried out. In the crystal structures there are only host-guest hydrogen bonds of O···H, N···H and S···H type. Owing to the comparable size of the two constituents neither host-host nor guest-guest secondary interactions occur. In the first thermal decomposition step a parallel release of ethanol and water was observed by simultaneous thermogravimetric and differential thermal analysis measurements. This indicates that some bonds of the metal complex unit and the host-guest secondary interactions in 1 and 2 are weaker than interactions in the pure drug. If an easy release of ethanol and water occurs during dissolution of 1 and 2, it might result in an improved bioavailability of the drug, which is soluble only in aqueous ethanol.

AB - Syntheses, crystal structures and comparative analytical investigations on the first two inclusion compounds of an antiepileptic drug, nitrazepam (1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one) are reported. The biologically active molecule forms isostructural clathrates with diaquadiethanolbis(isothiocyanato) complexes of both cobalt(II) and nickel(II) in molar ratios of 1:2 [M(NCS)2(C2H5OH)2 (H2O)2]·2C15H11 N3O3 (M = Co2+, 1, and M = Ni2+, 2). Detailed analyses of the structures, the secondary interactions, the neutral drug conformations, the FTIR spectra and thermal stabilities of the clathrates, in comparison with those of the crystalline nitrazepam, have been carried out. In the crystal structures there are only host-guest hydrogen bonds of O···H, N···H and S···H type. Owing to the comparable size of the two constituents neither host-host nor guest-guest secondary interactions occur. In the first thermal decomposition step a parallel release of ethanol and water was observed by simultaneous thermogravimetric and differential thermal analysis measurements. This indicates that some bonds of the metal complex unit and the host-guest secondary interactions in 1 and 2 are weaker than interactions in the pure drug. If an easy release of ethanol and water occurs during dissolution of 1 and 2, it might result in an improved bioavailability of the drug, which is soluble only in aqueous ethanol.

KW - Cobalt complexes

KW - Crystal structures

KW - Drug complexes

KW - Isothiocyanato complexes

KW - Nickel complexes

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U2 - 10.1016/S0020-1693(01)00375-9

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M3 - Article

VL - 315

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EP - 235

JO - Inorganica Chimica Acta

JF - Inorganica Chimica Acta

SN - 0020-1693

IS - 2

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