Substitution of all 20 hydrogens by fluorine atoms yields the relatively unstable perfluorododecahedrane CF, which was obtained in milligram quantities.  Trace amounts of the analogous  perchlorododecahedrane CCl were obtained, among other partially chlorinated derivatives, by reacting  dissolved in liquid chlorine under pressure at about 140 °C and under intense light for five days.  Complete replacement by heavier halogens seems increasingly difficult due to their larger size.  Half or more of the hydrogen atoms can be substituted by hydroxyl groups to yield polyols, but the extreme compound C(OH) remained elusive as of 2006. Amino-dodecahedranes comparable to amantadine have been prepared, but were more toxic and with weaker antiviral effects.
Annulated dodecahedrane structures have been proposed.