Encapsulation of platinum(II)-based DNA intercalators within cucurbit[6,7,8]urils.
The partial encapsulation of platinum(II)-based DNA intercalators of the type [Pt(5-Cl-phen)(ancillary ligand)](2+), where 5-Cl-phen is 5-chloro-1,10-phenanthroline and the ancillary ligand is ethylenediamine, (1S,2S)-diaminocyclohexane (S,S-dach) or (1R,2R)-diaminocyclohexane, within cucurbit[n]uril (CB[n], where n is 6, 7 or 8) has been examined by (1)H and (195)Pt NMR and mass spectrometry. For CB[7], the molecule encapsulates over the ancillary ligand of all metal complexes, whether this is ethylenediamine or diaminocyclohexane. For CB[8], encapsulation occurs over the sides of the 5-Cl-phen ligand at low [Pt(5-Cl-phen)(S,S-dach)](2+) (5CLSS) to CB[8] ratios (i.e. 0.25:1) but over the ancillary ligand at higher ratios (i.e. 2:1). For CB[6] binding, 5CLSS exhibits both portal and cavity binding, with the ancillary ligand displaying chemical shifts consistent with fast exchange kinetics on the NMR timescale for portal binding and slow exchange kinetics for cavity binding. Binding constants could not be determined using UV-vis, circular dichroism or fluorescence spectrophotometry, but a binding constant for binding of 5CLSS to CB[6] of approximately 10(5) M(-1) was determined using (1)H NMR. Finally, the effect of CB[n] encapsulation on the cytotoxicity of the metal complexes was examined using L1210 murine leukaemia cells in vitro growth inhibition assays. The cytotoxicity is highly dependent on both the metal complex and the CB[n] size, and whilst CB[7] and CB[8] generally decreased cytotoxicity, it was found that CB[6] increased the cyotoxicity of 5CLSS up to 2.5-fold.
Kemp
Sharon
S
School of Biomedical and Health Sciences, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 1797, Australia.
Wheate
Nial J
NJ
Wang
Shaoyu
S
Collins
J Grant
JG
Ralph
Stephen F
SF
Day
Anthony I
AI
Higgins
Vincent J
VJ
Aldrich-Wright
Janice R
JR
D000818:Animals; D001952:Bridged-Ring Compounds / Q000737:chemistry*; D002214:Capsules / Q000737:chemistry; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D007093:Imidazoles / Q000737:chemistry*; D007364:Intercalating Agents / Q000737:chemistry*; D007938:Leukemia / Q000188:drug therapy*; D051379:Mice; D015394:Molecular Structure; D010984:Platinum / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils
D001952:Bridged-Ring Compounds; D002214:Capsules; D004247:DNA; D007093:Imidazoles; D007364:Intercalating Agents; D010984:Platinum; C456276:cucurbit(7)uril; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils; C507198:cucurbit(8)uril; C454805:cucurbit(6)uril