Drug delivery of lipophilic pyrenyl derivatives by encapsulation in a water soluble metalla-cage

The self-assembly of 2,4,6-tris(pyridin-4-yl)-1,3,5-triazine (tpt) triangular panels with p-cymene (p-Pr(i)C(6)H(4)Me) ruthenium building blocks and 2,5-dioxydo-1,4-benzoquinonato (dobq) bridges, in the presence of a functionalised pyrenyl derivative (pyrene-R), affords the triangular prismatic host-guest compounds [(pyrene-R) [symbol: see text] Ru(6)(p-Pr(i)C(6)H(4)Me)(6)(tpt)(2)(dobq)(3)](6+) ([(pyrene-R) [symbol: see text] 1](6+)). The inclusion of eight mono-substituted pyrenyl derivatives including biologically relevant structures (a = 1-pyrenebutyric acid, b = 1-pyrenebutanol, c = 1-pyrenemethylamine, d = 1-pyrenemethylbutanoate, e = 1-(4,6-dichloro-1,3,5-triazin-2-yl)pyrene, f = N-hexadecylpyrene-1-sulfonamide, g = pyrenyl ethacrynic amide and h = 2-(pyren-1-ylmethylcarbamoyl) phenyl acetate), and a di-substituted pyrenyl derivative (i = 1,8-bis(3-methyl-butyn-1-yl-3-ol)pyrene), has been accomplished. The carceplex nature of these systems with the pyrenyl moiety being firmly encapsulated in the hydrophobic cavity of the cage with the functional groups pointing outwards was confirmed by NMR ((1)H, 2D, DOSY) spectroscopy and electrospray ionization mass spectrometry (ESI-MS). The cytotoxicities of these water-soluble compounds have been established using human ovarian A2780 cancer cells. All the host-guest systems are more cytotoxic than the empty cage itself [1][CF(3)SO(3)](6) (IC(50) = 23 microM), the most active carceplex [f [symbol: see text] 1][CF(3)SO(3)](6) is an order of magnitude more cytotoxic.