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

Abstract

The self-assembly of 2,4,6-tris(pyridin-4-yl)-1,3,5-triazine (tpt) triangular panels with p-cymene (p-PrⁱC₆H₄Me) 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) ⊂ Ru₆(p-PrⁱC₆H₄Me)₆(tpt)₂(dobq)₃]⁶⁺ ([(pyrene–R) ⊂ 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 (¹H, 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][CF₃SO₃]₆ (IC₅₀ = 23 μM), the most active carceplex [f ⊂ 1][CF₃SO₃]₆ is an order of magnitude more cytotoxic.