Lenses are (were) usually designed to reach optimal performance at (from) certain f/stop - because different optical aberrations are affected differently when 'stopping down'. Good example are many large format lenses where the 'wide open' aperture (anywhere down to f/9 depending on the lens) gets only used for focusing and one stops down to at least f/16 to get the best optical performance. Of course - with large format one in general does not use large enlargement factors so even f/45 (or less with 8x10" or bigger) is not a problem.
Tesar lenses were/are known for very good performance on axis even at larger aperture, but require stopping down (my experience with Rolleiflex T says at least to f/8) to improve the corners.
I am not going to dip into diffraction, because whether one sees it in the final print depends on several factors and it would probably be easier to simply test it than discuss it to death. The DOF calculators (+ the knowledge of the dpi in the printing) on the web give a good starting point. But I would not expect diffraction problem down to f/22 with 10" prints from 6x6.