Twisted Chemistry

Twisted Chemistry

You may have heard of the 2004 film Twisted starring Ashley Judd and Andy Garcia, or the popular iced tea product by the same name, or even one of several pop songs that have been recorded over the years with the same title.  However, chemistry performed in the laboratory of Professor Arthur Greenberg is far and away the most interesting twisted reference of recent times. In a recently accepted paper, Professor Greenberg and graduate student Brian Sliter reveal the twisted details of 1-azabicyclo[3.3.1]nonan-2-one, an amide that behaves like no other.  
Normal amides and undistorted lactams protonate on oxygen: B3LYP/6-31G* calculations (gas phase) indicate this is the favored mode by some 14-15 kcal/mol. In contrast, the severely-distorted (orthogonal) amide linkage in 1-azabicyclo[2.2.2]octan-2-one ("2-quinuclidone") is protonated on nitrogen: B3LYP/6-31G* calculations indicate this is the favored mode by over 20 kcal/mol. Where is (are) the "crossover" point(s) in distorted or twisted amides and lactams? One such "crossover" point is 1-azabicyclo[3.3.1]nonan-2-one, calculated to have a resonance energy that is 50-60% that of the 20 kcal/mol of typical amides and lactams. Experimental studies of 1-azabicyclo[3.3.1]nonan-2-one in trifluoroacetic acid, sulfuric acid and triflic acid using 1H and 13C NMR spectroscopy, COSY, NOESY, and ultraviolet spectroscopy are revealing and may shed light on the nature of enzyme binding and catalysis in proteolysis.  The entire twisted story has been accepted for publication.  Check back soon for the electronic link.

You may have heard of the 2004 film Twisted starring Ashley Judd and Andy Garcia, or the popular iced tea product by the same name, or even one of several pop songs that have been recorded over the years with the same title.  However, chemistry performed in the laboratory of Professor Arthur Greenberg is far and away the most interesting twisted reference of recent times. In a recently published paper, Professor Greenberg and graduate student Brian Sliter reveal the twisted details of 1-azabicyclo[3.3.1]nonan-2-one, an amide that behaves like no other.  


Normal amides and undistorted lactams protonate on oxygen: B3LYP/6-31G* calculations (gas phase) indicate this is the favored mode by some 14-15 kcal/mol. In contrast, the severely-distorted (orthogonal) amide linkage in 1-azabicyclo[2.2.2]octan-2-one ("2-quinuclidone") is protonated on nitrogen: B3LYP/6-31G* calculations indicate this is the favored mode by over 20 kcal/mol. Where is (are) the "crossover" point(s) in distorted or twisted amides and lactams? One such "crossover" point is 1-azabicyclo[3.3.1]nonan-2-one, calculated to have a resonance energy that is 50-60% that of the 20 kcal/mol of typical amides and lactams. Experimental studies of 1-azabicyclo[3.3.1]nonan-2-one in trifluoroacetic acid, sulfuric acid and triflic acid using 1H and 13C NMR spectroscopy, COSY, NOESY, and ultraviolet spectroscopy are revealing and may shed light on the nature of enzyme binding and catalysis in proteolysis.  The entire twisted story has been accepted for publication and can be found at: http://pubs.acs.org/doi/abs/10.1021/jo200195a.