I haven't come up with an explanation for this yet, but on my minions, the mouse 'hot spots' for clicking on chests are all messed up. The game will pretend my mouse is not actually over the chest. If I move the mouse slowly around the chest I can sometimes find a spot that it finally 'likes' and will let me click on. Another solution is to rotate the view a bit to get at it from a different angle.

Maybe that's what you're running into too?