The Single Six frame is massively over built for the factory chamberings, but the metalurgy may not always be up to the more powerful cartridges.
I got my Single Six .22 Magnum as a near junker, badly rusted with damaged grip frame and broken grips.
The cylinder gap was way out there, and the barrel breech was at an angle to the cylinder face. There was a lot of cylinder slap.
I used a chunk of very hard walnut board as a mallet and bracing the rear of the frame used the edge of the board to deliver rapid hard blows to the front of the frame at the cylinder pin opening. The wood was hard enough to transfer energy but not hard enough to upset the steel.
After a few hundred judicous blows, checking the fit often, I brought the frame back to near its orginal shape. The barrel breech and cylinder face are now paralel and gap is within reason. Couldn't take out all the cylinder slap but a .002 washer fixed that up just fine.
The rear of the cylinder showed signs of fanning and out of time strikes, so it may be that out of time firings had been the main culprit.
Still yet, the steel seemed a hair soft for the purpose. Could be a rare flaw due to improper heat treatment, but one should make sure how tough their particular frame is before proceeding with any conversion to hotter cartridges.
For a five or four chamber conversion I'd consider a hammer mounted firing pin with between the chambers slots in the cylinder to hold the pin between chambers. The old Colt cap and ball revolvers and several early cartridge revolvers used this safety system and it works well.
The four chamber colt House pistol with cloverleaf arrangement used the between chambers hammer position which allowed a slimmer profile when carrying in a pocket.
Some designers added extra locking bolt cuts in the cylinder.