Cucurbit[n]uril binding of platinum anticancer complexes

N.J. Wheate, Damian P. Buck, Anthony I. Day, J.G. Collins

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

The encapsulation of cisplatin by cucurbit[7]uril (Q[7]) and multinuclear platinum complexes linked via a 4,4′-dipyrazolylmethane (dpzm) ligand by Q[7] and cucurbit[8]uril (Q[8]) has been studied by NMR spectroscopy and molecular modelling. The NMR studies suggest that some cisplatin binds in the cucurbituril cavity, while cis-[PtCl(NH3)2(H2O)]+ only binds at the portals. Alternatively, the dpzm-linked multinuclear platinum complexes are quantitatively encapsulated within the cavities of both Q[7] and Q[8]. Upon encapsulation, the non-exchangeable proton resonances of the multinuclear platinum complexes show significant upfield shifts in 1H NMR spectra. The H3/H3* resonances shift upfield by 0.08 to 0.55 ppm, the H5/H5* shift by 0.9 to 1.6 ppm, while the methylene resonances shift by 0.74 to 0.88 ppm. The size of the resonance shift is dependent on the cavity size of the encapsulating cucurbituril, with Q[7] encapsulation producing larger shifts than Q[8]. The upfield shifts of the dpzm resonances observed upon cucurbituril encapsulation indicate that the Q[7] or Q[8] is positioned directly over the dpzm linking ligand. The terminal platinum groups of trans-[{PtCl(NH3)2}2μ-dpzm]2+ (di-Pt) and trans-[trans-{PtCl(NH3)2}2-trans-{Pt(dpzm)2(NH3)2}]4+ (tri-Pt) provide a barrier to the on and off movement of cucurbituril, resulting in binding kinetics that are slow on the NMR timescale for the metal complex. Although the dpzm ligand has relatively few rotamers, encapsulation by the larger Q[8] resulted in a more compact di-Pt conformation with each platinum centre retracted further into each Q[8] portal. Encapsulation of the hydrolysed forms of di-Pt and tri-Pt is considerably slower than for the corresponding Cl forms, presumably due to the high-energy cost of passing the +2 platinum centres through the cucurbituril portals. The results of this study suggest that cucurbiturils could be suitable hosts for the pharmacological delivery of multinuclear platinum complexes
LanguageEnglish
Pages451-458
Number of pages7
JournalDalton Transactions
Issue number3
DOIs
Publication statusPublished - 21 Jan 2006

Fingerprint

Platinum
Encapsulation
Nuclear magnetic resonance
Ligands
Cisplatin
Molecular modeling
Coordination Complexes
Nuclear magnetic resonance spectroscopy
Conformations
cucurbituril
Protons
Kinetics
Costs

Keywords

  • cancer
  • cucurbit[n]uril
  • cucurbit[n]uril binding
  • platinum
  • anticancer
  • complexes
  • human ovarian cancer
  • dna-binding
  • cisplating resistance
  • cell lines
  • triplatinum complex
  • bbr 3464
  • cucurbituril
  • cytotoxicity
  • bbr3464
  • agents

Cite this

Wheate, N. J., Buck, D. P., Day, A. I., & Collins, J. G. (2006). Cucurbit[n]uril binding of platinum anticancer complexes. Dalton Transactions, (3), 451-458. https://doi.org/10.1039/b513197a
Wheate, N.J. ; Buck, Damian P. ; Day, Anthony I. ; Collins, J.G. / Cucurbit[n]uril binding of platinum anticancer complexes. In: Dalton Transactions. 2006 ; No. 3. pp. 451-458.
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Wheate, NJ, Buck, DP, Day, AI & Collins, JG 2006, 'Cucurbit[n]uril binding of platinum anticancer complexes' Dalton Transactions, no. 3, pp. 451-458. https://doi.org/10.1039/b513197a

Cucurbit[n]uril binding of platinum anticancer complexes. / Wheate, N.J.; Buck, Damian P.; Day, Anthony I.; Collins, J.G.

In: Dalton Transactions, No. 3, 21.01.2006, p. 451-458.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cucurbit[n]uril binding of platinum anticancer complexes

AU - Wheate, N.J.

AU - Buck, Damian P.

AU - Day, Anthony I.

AU - Collins, J.G.

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N2 - The encapsulation of cisplatin by cucurbit[7]uril (Q[7]) and multinuclear platinum complexes linked via a 4,4′-dipyrazolylmethane (dpzm) ligand by Q[7] and cucurbit[8]uril (Q[8]) has been studied by NMR spectroscopy and molecular modelling. The NMR studies suggest that some cisplatin binds in the cucurbituril cavity, while cis-[PtCl(NH3)2(H2O)]+ only binds at the portals. Alternatively, the dpzm-linked multinuclear platinum complexes are quantitatively encapsulated within the cavities of both Q[7] and Q[8]. Upon encapsulation, the non-exchangeable proton resonances of the multinuclear platinum complexes show significant upfield shifts in 1H NMR spectra. The H3/H3* resonances shift upfield by 0.08 to 0.55 ppm, the H5/H5* shift by 0.9 to 1.6 ppm, while the methylene resonances shift by 0.74 to 0.88 ppm. The size of the resonance shift is dependent on the cavity size of the encapsulating cucurbituril, with Q[7] encapsulation producing larger shifts than Q[8]. The upfield shifts of the dpzm resonances observed upon cucurbituril encapsulation indicate that the Q[7] or Q[8] is positioned directly over the dpzm linking ligand. The terminal platinum groups of trans-[{PtCl(NH3)2}2μ-dpzm]2+ (di-Pt) and trans-[trans-{PtCl(NH3)2}2-trans-{Pt(dpzm)2(NH3)2}]4+ (tri-Pt) provide a barrier to the on and off movement of cucurbituril, resulting in binding kinetics that are slow on the NMR timescale for the metal complex. Although the dpzm ligand has relatively few rotamers, encapsulation by the larger Q[8] resulted in a more compact di-Pt conformation with each platinum centre retracted further into each Q[8] portal. Encapsulation of the hydrolysed forms of di-Pt and tri-Pt is considerably slower than for the corresponding Cl forms, presumably due to the high-energy cost of passing the +2 platinum centres through the cucurbituril portals. The results of this study suggest that cucurbiturils could be suitable hosts for the pharmacological delivery of multinuclear platinum complexes

AB - The encapsulation of cisplatin by cucurbit[7]uril (Q[7]) and multinuclear platinum complexes linked via a 4,4′-dipyrazolylmethane (dpzm) ligand by Q[7] and cucurbit[8]uril (Q[8]) has been studied by NMR spectroscopy and molecular modelling. The NMR studies suggest that some cisplatin binds in the cucurbituril cavity, while cis-[PtCl(NH3)2(H2O)]+ only binds at the portals. Alternatively, the dpzm-linked multinuclear platinum complexes are quantitatively encapsulated within the cavities of both Q[7] and Q[8]. Upon encapsulation, the non-exchangeable proton resonances of the multinuclear platinum complexes show significant upfield shifts in 1H NMR spectra. The H3/H3* resonances shift upfield by 0.08 to 0.55 ppm, the H5/H5* shift by 0.9 to 1.6 ppm, while the methylene resonances shift by 0.74 to 0.88 ppm. The size of the resonance shift is dependent on the cavity size of the encapsulating cucurbituril, with Q[7] encapsulation producing larger shifts than Q[8]. The upfield shifts of the dpzm resonances observed upon cucurbituril encapsulation indicate that the Q[7] or Q[8] is positioned directly over the dpzm linking ligand. The terminal platinum groups of trans-[{PtCl(NH3)2}2μ-dpzm]2+ (di-Pt) and trans-[trans-{PtCl(NH3)2}2-trans-{Pt(dpzm)2(NH3)2}]4+ (tri-Pt) provide a barrier to the on and off movement of cucurbituril, resulting in binding kinetics that are slow on the NMR timescale for the metal complex. Although the dpzm ligand has relatively few rotamers, encapsulation by the larger Q[8] resulted in a more compact di-Pt conformation with each platinum centre retracted further into each Q[8] portal. Encapsulation of the hydrolysed forms of di-Pt and tri-Pt is considerably slower than for the corresponding Cl forms, presumably due to the high-energy cost of passing the +2 platinum centres through the cucurbituril portals. The results of this study suggest that cucurbiturils could be suitable hosts for the pharmacological delivery of multinuclear platinum complexes

KW - cancer

KW - cucurbit[n]uril

KW - cucurbit[n]uril binding

KW - platinum

KW - anticancer

KW - complexes

KW - human ovarian cancer

KW - dna-binding

KW - cisplating resistance

KW - cell lines

KW - triplatinum complex

KW - bbr 3464

KW - cucurbituril

KW - cytotoxicity

KW - bbr3464

KW - agents

UR - http://dx.doi.org/10.1039/b513197a

U2 - 10.1039/b513197a

DO - 10.1039/b513197a

M3 - Article

SP - 451

EP - 458

JO - Dalton Transactions

T2 - Dalton Transactions

JF - Dalton Transactions

SN - 1477-9226

IS - 3

ER -