Research papers Bender's initial work concerned mechanisms of chemical reactions, and although this continued through his career he became increasingly interested in enzyme mechanisms, especially that of α-
chymotrypsin. Later he broadened his interest to encompass other enzymes, such as
acetylcholinesterase and
carboxypeptidase, and others. Bender pioneered the use of
p-nitrophenyl acetate as a model substrate for studying proteolysis, as it is particularly convenient in spectroscopic experiments. He likewise used imidazole as a model catalyst for shedding light on enzyme action. He also studied artificial enzymes, starting with modified
subtilisin in which a serine residue was replaced by cysteine (replacing an ester group with a thiol). Polgar and Bender laid stress on the fact that the modified enzyme was catalytically active, whereas Koshland and Neet, who made essentially the same observation the same year, drew the opposite conclusion, that despite replacing group with one in principle more reactive, the modified enzyme was less effective as a catalyst than the unmodified enzyme. Philipp and Bender later did a detailed study of the catalytic differences between native subtilisin and thiolsubtilisin. Bender also studied other artificial enzymes, such as cycloamyloses, that were not simply modified natural enzymes. Bender may have been the first to recognize that the specificity constant (k_\mathrm{cat}/K_\mathrm{m}, the ratio of catalytic constant to
Michaelis constant) provides the best measure of enzyme specificity, and to use the term
specificity constant for it, as later recommended by the
IUBMB. Philipp and Bender proposed that this specificity constant is the same as the second-order rate constant for enzyme-substrate binding for the most active substrates.
Reviews Bender authored or co-authored several reviews, for example summarizing several years' work on α-chymotrypsin, and proteolytic enzymes in general.
Books Bender's books primarily concerned catalysis, especially catalysis by enzymes and its underlying chemistry, and also cyclodextrin chemistry; ==Bender Distinguished Summer Lecturers==