When it comes to compatability with trains there is a sliding scale between being able to physically couple (without the need for adapters of barrier coaches) to being able to run in multiple in passenger service. Phycically coupling requires the same sort of coupler. In extream cases similar but different couplers could couple in restricted circumstances (e.g a Buckeye and Tightlock, same physical design but different height), but physical compatability usually requires the same type of coupler (I'm not sure if very similar types for example a Dellner and Sharfenberg could physically couple). For anything but low speed running, brake compatability is needed. In the days of Westinghouse Automatic Air Brakes, that was a given (with the ovious exception of vacume braked stock), even if in some cases adapters might be needed for the pipes (e.g to couple the high level air pipes on EMU to the conventional pipes on a loco), but with full Electropnumatic systems it's another matter. They need to connect, and they need to be able to talk the same language. To run in multiple the multiple working systems need to be compatable, so that the engines or motors on one type can be controlled from the other type. An example that doesn't get quite this far would be two locos with different multiple working systems (say a Blue Star fitted 37 and a AAR fitted 66), they can couple, they both are braked, but one would have to be dead (or driven seperatly). To run together in passenger service you need to make sure things like door controls, alarms, PA etc will work properly in multiple. Of cource there is another level of compatability in terms of things like power supply. A 360 and a 450 might be able to work together in multiple (who knows, who cares), but oviously would have the problem that other than very short sections of line, only one could actually take power, so unless they were being used between Farringdon and City Thameslink, or one or both are DVed in the future, it's a moot point (hence who cares). Moot (or Moo, like a cows opinion). Performance compatability could be an issue too, but it's never stopped 15X types and 170s working together with differing performance for all 7 types and 3 different top speeds, but EMUs only ever seem to work with others of near identical performance.
When it comes to 25kV fitted lengthened Voyagers, whilst as has been said they would be fine under the wires (as long as the additional coaches were motored anyway), when off the wires performance would suffer greatly. Reaching 125mph isn't the problem, it's acceleration on a unit that is geared for 125mph running, and in the case of the 221 damned heavy too (thanks to the tilt gear). A HST on one powercar can reach 125mph (I've got a feeling they can, or at least close, on the level, but they could downhill) but can't climb the Lickey Incline unassisted and will stuggle up many lesser gradients, and be very slow from a stand. Since you would unlikely get any significant performance advantage under the wires (Voyagers are afterall pretty nippy and will leave most EMUs standing) then lost performance off the wires would result in increased journey times.