If you want to account for "taking up space between molecules" it's easy to do.
Essentially, when the sugars dissolve, they increase the volume of solution but they also raise its density (measured in specific gravity). It's an easy relation:
(Volume of water + volume of sugar) / estimated gravity = volume of boil
3 pounds of LME will raise the gravity of one gallon of water by appoximately 0.1 SG. 4 pounds would raise one gallon by about 0.13. We'll ballpark the volume of 4 pounds of LME at about half a gallon, as above.
So, say you've got 1.5 gallons of water and 4lb (appx. 1/2 gal) of LME. Estimated SG of the boil will be about 1.13.
(1.5 + .5) / 1.13 = ~1.75 gallons (or 7 quarts)
This doesn't mean that you can use a 7-quart pot, though. You've got to have room to stir and account for bubbling/foaming. You *might* be able to get away with an 8-quart pot but if you can use a 12-quart, do it.