.22 LR is the preferred round for assassins, spies, hitmen, etc.
Exactly .22 LR long barrel pistols or rifles can be equipped w ith home made siliencers (PVC pipe and fittings) ...make next to now noise - fairly accurate at near to medium range...
But back to large caliber weapons... no doubt a big .45. 50 or .357 / .44 magnum will knock down a bad guy - and he will probably stay down. Experienced and trained and in shape shooters can hit what they aim at with these ‘Make my Day’ guns... But most people in home defense situations are not of this cut. For home defense for most women I recommend one of the .410 shotguns with a pistol grip and as short a barrel as the law allows. Or one of the revolvers that shoots the .410 round ... both using big shot - not necessarily buck shot and certainly not bird shot.