Honestly, if one wanted to build a medium-frame revolver in a bigbore semi-auto caliber, .45 ACP would probably be the way to go. Taurus made the Model 455 in that caliber for years (as well as the Model 450 in .45 Long Colt) so we already know that it can be done. With a 185gr loading like Winchester's Silvertip, you can fairly easily match the ballistics of a 180gr .40 S&W and do so with a larger diameter bullet at lower pressure (SAAMI max for standard pressure .45 ACP is 21,000psi and .45 ACP +P is 23,000psi). You could also go with .45 Long Colt as it's pressure is even lower at 14,000psi.
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