Homolytic Constants in the Correlation of Chloramphenicol Structure with Activity
There hit:, been corisiderable interest in structure--activity qtudies of chloramphenicol derivatives because of the particular effectiveness of the parent compound in fighting infection:, cauied by gram-negative bacteria. aiit to ninny other antibiotics.2 Except f'oi, structural vari:ttioiii i i i the :icylamirio group, vuriat iori in the side chain of chlormipheriicol results in a h r g c drcrease in a c t i ~ i t y . " - ~0 1 1 the other hand, variatiotii III the (jura positioii of thcx :iryl ring teem to tw powiblc without 5uch great lo:,:, i t i i7or thii reason JVC' :,h:ill bc prim:irily coriceriied u ith variations in 1' of itructiirc I. The first quaiitit:itive correlatioirfiof variOH
SHCOCHCI
1
iation:, of I confirmed the qualitative observation of Shemyakin that electron withdrawal by ~ubstituerits iiicreabed activity. Equation 1 for E'scherichiu coli, d though not a very high correlation, ihowedGthat nctivity depended on both electronic :md hydrophobic properties o f t h e substitlietit. 111c y 1 , urnrepresents the log HIt
O.:~(\T
=
-0.747?
+ l.h'lu,
+ + 0.62
/I
I
10 0.hZ-t
9
O.T,.i.i
(1)
electronic effect of the hubstituerit 011 the ortho position. e employed because they yielded :I The UnLc0llSt:LIltS ation than up. For eq 1, n repslightly hetter c thr number of data points, 1 is the correla t 1011 ' rrit, arid s is the ytandard deviation. Using :i much more accurate method of assay, termed rm'croh2al kiriefir, Garrett, et reinvestigated a set of ~hlor:rmphcnicol:, ii*iiig E. c .' Garrett's choice of hub:,titiicrits g:tvc. :i bettcr spread of electronic values :~lthoughnot, a* great a rmge of hydrophobic charactel. :I$ Sheinyaliiii's. Hii dat :I. :iq well a s physicochemicnl cori
