A chemical preformulation study of a host-guest complex of cucurbit[7]uril and a multinuclear platinum agent for enhanced anticancer drug delivery

Alan R. Kennedy, Alastair J. Florence, Fiona J. McInnes, Nial J. Wheate

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Single crystal and powder X-ray diffraction have been used to examine the host-guest complex of cucurbit[7]uril (CB[7]) and the model dinuclear platinum anticancer complex trans-[{PtCl(NH3)2}2-dpzm]2+ (di-Pt, dpzm= 4,4-dipyrazolylmethane). The single crystal structure shows that the host-guest complex forms with the di-Pt dpzm ligand within the CB[7] cavity and with the platinum groups just beyond the macrocycle portals. Binding is stabilised through hydrophobic interactions and six hydrogen bonds between the platinum ammine ligands and the dpzm pyrazole amine to the CB[7] carbonyls. Each host-guest complex crystallises with two chloride counterions and 5.5 water molecules. The unit cell comprises four asymmetric units, each of which contains three crystallographically independent CB[7]-di-Pt moieties. X-Ray powder diffraction demonstrated structural consistency of the bulk crystals with a single polycrystalline phase that is identical with the single crystal structure. Finally, the effect of CB[7] encapsulation of the thermal stability of di-Pt was examined by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). From the TGA experiments it was found that free CB[7] and the CB[7]-di-Pt complex lose 11 and 3.5% of their mass respectively, through the loss of water molecules, upon heating to 160 °C. The DSC results showed that the free dpzm ligand melts between 186 and 199 °C, with a standard enthalpy of fusion of 27.92 kJ mol-1. As a 2+ inorganic salt the metal complex does not melt but undergoes several decomposition events between 140 and 290 °C. Encapsulation by CB[7] completely stabilises di-Pt with no decomposition of either the macrocycle or metal complex at temperatures up to 290 °C.
LanguageEnglish
Pages7695-7700
Number of pages6
JournalDalton Transactions
Volume2009
Issue number37
DOIs
Publication statusPublished - Jul 2009

Fingerprint

Platinum
Drug delivery
Coordination Complexes
Single crystals
Ligands
Encapsulation
X ray powder diffraction
Thermogravimetric analysis
Differential scanning calorimetry
Crystal structure
Decomposition
Molecules
cucurbit(7)uril
Water
Amines
Chlorides
Enthalpy
Hydrogen bonds
Thermodynamic stability
Fusion reactions

Keywords

  • cucurbit[7]uril
  • multinuclear platinum agent
  • anticancer drug delivery
  • pharmacology

Cite this

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title = "A chemical preformulation study of a host-guest complex of cucurbit[7]uril and a multinuclear platinum agent for enhanced anticancer drug delivery",
abstract = "Single crystal and powder X-ray diffraction have been used to examine the host-guest complex of cucurbit[7]uril (CB[7]) and the model dinuclear platinum anticancer complex trans-[{PtCl(NH3)2}2-dpzm]2+ (di-Pt, dpzm= 4,4-dipyrazolylmethane). The single crystal structure shows that the host-guest complex forms with the di-Pt dpzm ligand within the CB[7] cavity and with the platinum groups just beyond the macrocycle portals. Binding is stabilised through hydrophobic interactions and six hydrogen bonds between the platinum ammine ligands and the dpzm pyrazole amine to the CB[7] carbonyls. Each host-guest complex crystallises with two chloride counterions and 5.5 water molecules. The unit cell comprises four asymmetric units, each of which contains three crystallographically independent CB[7]-di-Pt moieties. X-Ray powder diffraction demonstrated structural consistency of the bulk crystals with a single polycrystalline phase that is identical with the single crystal structure. Finally, the effect of CB[7] encapsulation of the thermal stability of di-Pt was examined by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). From the TGA experiments it was found that free CB[7] and the CB[7]-di-Pt complex lose 11 and 3.5{\%} of their mass respectively, through the loss of water molecules, upon heating to 160 °C. The DSC results showed that the free dpzm ligand melts between 186 and 199 °C, with a standard enthalpy of fusion of 27.92 kJ mol-1. As a 2+ inorganic salt the metal complex does not melt but undergoes several decomposition events between 140 and 290 °C. Encapsulation by CB[7] completely stabilises di-Pt with no decomposition of either the macrocycle or metal complex at temperatures up to 290 °C.",
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A chemical preformulation study of a host-guest complex of cucurbit[7]uril and a multinuclear platinum agent for enhanced anticancer drug delivery. / Kennedy, Alan R.; Florence, Alastair J.; McInnes, Fiona J.; Wheate, Nial J.

In: Dalton Transactions, Vol. 2009, No. 37, 07.2009, p. 7695-7700.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A chemical preformulation study of a host-guest complex of cucurbit[7]uril and a multinuclear platinum agent for enhanced anticancer drug delivery

AU - Kennedy, Alan R.

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AU - Wheate, Nial J.

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N2 - Single crystal and powder X-ray diffraction have been used to examine the host-guest complex of cucurbit[7]uril (CB[7]) and the model dinuclear platinum anticancer complex trans-[{PtCl(NH3)2}2-dpzm]2+ (di-Pt, dpzm= 4,4-dipyrazolylmethane). The single crystal structure shows that the host-guest complex forms with the di-Pt dpzm ligand within the CB[7] cavity and with the platinum groups just beyond the macrocycle portals. Binding is stabilised through hydrophobic interactions and six hydrogen bonds between the platinum ammine ligands and the dpzm pyrazole amine to the CB[7] carbonyls. Each host-guest complex crystallises with two chloride counterions and 5.5 water molecules. The unit cell comprises four asymmetric units, each of which contains three crystallographically independent CB[7]-di-Pt moieties. X-Ray powder diffraction demonstrated structural consistency of the bulk crystals with a single polycrystalline phase that is identical with the single crystal structure. Finally, the effect of CB[7] encapsulation of the thermal stability of di-Pt was examined by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). From the TGA experiments it was found that free CB[7] and the CB[7]-di-Pt complex lose 11 and 3.5% of their mass respectively, through the loss of water molecules, upon heating to 160 °C. The DSC results showed that the free dpzm ligand melts between 186 and 199 °C, with a standard enthalpy of fusion of 27.92 kJ mol-1. As a 2+ inorganic salt the metal complex does not melt but undergoes several decomposition events between 140 and 290 °C. Encapsulation by CB[7] completely stabilises di-Pt with no decomposition of either the macrocycle or metal complex at temperatures up to 290 °C.

AB - Single crystal and powder X-ray diffraction have been used to examine the host-guest complex of cucurbit[7]uril (CB[7]) and the model dinuclear platinum anticancer complex trans-[{PtCl(NH3)2}2-dpzm]2+ (di-Pt, dpzm= 4,4-dipyrazolylmethane). The single crystal structure shows that the host-guest complex forms with the di-Pt dpzm ligand within the CB[7] cavity and with the platinum groups just beyond the macrocycle portals. Binding is stabilised through hydrophobic interactions and six hydrogen bonds between the platinum ammine ligands and the dpzm pyrazole amine to the CB[7] carbonyls. Each host-guest complex crystallises with two chloride counterions and 5.5 water molecules. The unit cell comprises four asymmetric units, each of which contains three crystallographically independent CB[7]-di-Pt moieties. X-Ray powder diffraction demonstrated structural consistency of the bulk crystals with a single polycrystalline phase that is identical with the single crystal structure. Finally, the effect of CB[7] encapsulation of the thermal stability of di-Pt was examined by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). From the TGA experiments it was found that free CB[7] and the CB[7]-di-Pt complex lose 11 and 3.5% of their mass respectively, through the loss of water molecules, upon heating to 160 °C. The DSC results showed that the free dpzm ligand melts between 186 and 199 °C, with a standard enthalpy of fusion of 27.92 kJ mol-1. As a 2+ inorganic salt the metal complex does not melt but undergoes several decomposition events between 140 and 290 °C. Encapsulation by CB[7] completely stabilises di-Pt with no decomposition of either the macrocycle or metal complex at temperatures up to 290 °C.

KW - cucurbit[7]uril

KW - multinuclear platinum agent

KW - anticancer drug delivery

KW - pharmacology

U2 - 10.1039/b907917c

DO - 10.1039/b907917c

M3 - Article

VL - 2009

SP - 7695

EP - 7700

JO - Dalton Transactions

T2 - Dalton Transactions

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SN - 1477-9226

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