caution : ipa / no and certain other 
 diazeniumdiolates have shown a tendency to dissociate rapidly and 
 unexpectedly and hence should be handled with due care .
ultraviolet ( uv ) spectra were recorded on a diode array spectrophotometer . 
 nuclear magnetic resonance ( nmr )
spectra were collected with a 400 
 mhz spectrometer using appropriate deuterated solvents with chemical 
 shifts reported in parts per million downfield from tetramethylsilane 
 or 2,2,3,3-tetradeuterotrimethylsilylpropionic acid .
ions for 
 high - resolution mass spectrometry were generated with electrospray 
 ionization and detected with a quadrupole time - of - flight mass analyzer .
ionic diazeniumdiolates are notoriously difficult to purify , 
 so it is correspondingly problematic to provide quantitative data 
 on the properties of the above - identified products .
nevertheless , 
 rough purity estimates could be derived from nmr experiments using 
 internal standards in alkaline solutions .
the result for 1a using potassium phthalimide as internal standard was a purity level 
 of 50% , with the remainder presumably consisting of naoh and other 
 uv- and nmr - silent constituents .
the purity of the 1b sample was similarly determined to be 80% using tert - butyl alcohol as internal standard .
these values were used as normalization 
 factors to establish the extinction coefficients as well as theoretical 
 yields of the various products summarized in table 1 .
a solution of 5.9 g ( 0.1 mol ) of acetamide 
 in 21.7 ml ( 0.1 mol ) of 4.6 m methanolic sodium methoxide , 10 ml of 
 methanol , and 50 ml of diethyl ether was charged with 40 psi of nitric 
 oxide and stirred under pressure at room temperature .
a precipitate 
 began to be visible within 2 h ; stirring was continued overnight , 
 giving a thick white precipitate .
the precipitate was collected by 
 filtration , washed with acetonitrile , and dried under vacuum to give 
 3.07 g of a white powder that was 50% pure according to the nmr / internal 
 standard method described above ( 10% yield ) . as a further purification 
 step , 2 g of crude 1a ( 50% pure , 7.1 mmol ) was dissolved 
 in 100 ml of methanol and stirred at room temperature .
the methanolic 
 solution was treated with 100 ml of ether , giving a white solid that 
 was collected by filtration and triturated with acetonitrile , then 
 dried in vacuo to give 1.7 g of product .
this process removed most 
 of the acetamide contaminant : uv ( in 0.01 m naoh ) max 252 nm ( 9.7 mm cm ) ; h nmr ( d2o / naod )  1.68 ( s ) ; c nmr ( d2o / naod )  20.8 , 177.1 .
a solution of 9.1 g ( 0.075 mol ) of nicotinamide in 30 
 ml of methanol was treated with 15.2 ml ( 0.07 mol ) of 4.6 m methanolic 
 sodium methoxide . to the solution
was added 50 ml of ether , after 
 which the vessel was degassed and charged with 50 psi of nitric oxide . 

the solution was stirred at room temperature ; after 72 h , the pressure 
 was released and the white precipitate was collected by filtration . 

the solid was washed with acetonitrile and dried under vacuum to give 
 3.91 g of 1b ( 80% pure by the internal standard nmr method 
 described above , 20% yield ) as a powder : uv ( 0.01 m naoh ) max 250 nm ( 11.8 mm cm ) ; h nmr ( d2o / naod ) 
7.507.56 
 ( m , 1h ) , 8.238.28 ( m , 1h ) , 8.598.63 ( m , 1h ) , 8.938.96 
 ( m , 1h ) ; c nmr ( d2o / naod )  123.8 , 132.6 , 
 136.4 , 147.7 , 150.0 , 171.4 . to a slurry of 252 mg of 1a ( 0.89 mmol ) and 250 mg of anhydrous sodium carbonate in 10 ml of 
 dmf at 0 c
was added 438 l ( 3.6 mmol ) of benzyl bromide ; 
 the resulting slurry was stirred at 0 c with gradual warming 
 to room temperature . after being stirred overnight , the reaction mixture 

was cooled to 80 c and placed in a lyophilizer ; on evaporation , 
 the solid residue was extracted with dichloromethane . the organic 
 layer was dried over sodium sulfate , filtered through a layer of magnesium 
 sulfate , and evaporated to give 229 mg of an oil .
the crude product 
 was chromatographed on a 25 g silica gel column and eluted with a 
 gradient from 100% methylene chloride to 70:30 methylene chloride / ethyl 
 acetate to give 102 mg ( 38% ) of pure 2 : mp 5758 
 c ; uv ( ethanol ) max 244 nm ( 11.1 mm cm ) ; h nmr ( cdcl3 )  
 7.35 ( s , 3h ) , 4.92 ( s , 2h ) , 5.18 ( s , 2h ) , 7.237.34 ( m , 10h ) 
 ; c nmr ( cdcl3 )  19.8 , 49 .
8 , 76.7 , 
 128.3 , 128.6 , 128.6 , 128.7 , 128.9 , 129.0 , 133.8 , 134.9 , 169.1 ; hrms 
 ( esi ) m / z calculated for c16h18n3o3m / z ( m + h ) 300.13427 , measured 
 300.1350 .
calcd for c16h17n3o3 : c , 64.20 ; h , 5.72 ; n , 14.04 .
found : c , 64.18 ; h , 5.81 ; 
 n , 14.29 . a slurry of 1.54 g of 80% pure 1b ( 6.1 mmol ) in 20 ml of n , n - dimethylformamide 
 was reacted with benzyl bromide ( 1.19 ml , 0.01 mol ) under conditions 
 similar to those used to prepare 2 ( previous paragraph ) 
 to give 420 mg ( 19% ) of pale brown solid .
the product was recrystallized 
 from hot water to give white x - ray quality crystals of 4b : mp 2368 c ; uv ( in 1:1 h2o / ch3cn ) max 239 nm ( 11.9 mm cm ) ; h nmr ( dmso - d6 )  5.07 ( s , 2h ) , 5.90 ( s , 2h ) , 7.337.52 ( m , 
 10h ) , 8.10 ( t , 1h ) j = 7.4 hz , 8.88 ( d , 1h ) j = 7.8 hz ; c nmr ( dmso - d6 )  63.1 , 73.0 , 127.7 , 127.9 , 128.1 , 128.3 , 128.8 , 129.3 , 
 129.3 , 134.4 , 137.1 , 139.0 , 143.7 , 143.8 , 144.7 , 162.6 ; hrms ( esi ) m / z calculated for c20h19n4o3 , 363.14517 , measured m / z 363.14567 . anal .
calcd for c20h18n4o30.25h2o : 
 c , 65.47 ; h , 5.08 ; n , 15.27 . found : c , 65.62 ; h , 4.84 ; n , 15.54 .
compound 1b ( 1.34 g , 80% pure , 5.3 
 mmol ) was dissolved in 50 ml of cold methanol ( 0 c ) and reacted 
 with dimethyl sulfate ( 1.52 ml , 16 mmol ) as above to give 1.8 g of 
 an orange oil .
the resulting crude product was chromatographed on 
 silica gel using a gradient from 100% dichloromethane to 50:50 dichloromethane / methanol 
 as the eluent .
a fraction containing 296 mg of product was concentrated , 
 whereupon the residual oil crystallized on standing .
recrystallization 
 from methanol gave 259 mg ( 23% ) of analytically pure 4b : mp 202205 c ; uv ( h2o ) max 239 nm ( 4.9 mm cm ) and max 268 nm ( 3.3 mm cm ) ; h nmr ( d2o )  4.11 
 ( s , 3h ) , 4.62 ( s , 3h ) , 8.11 ( br s , 1h ) , 8.89 ( br s , 2h ) , 9.21 ( br 
 s , 1h ) ; c nmr ( d2o )  51.2 , 64.0 , 130.6 , 
 138.9 , 146.5 , 147.6 , 149.2 , 170.0 ; hrms ( esi ) m / z calculated for c8h11n4o3m / z 211.08257 , 
 measured 211.08338 .
calcd for c8h10n4o30.25h2o : c , 44.75 ; h , 4.93 ; 
 n , 26.10 . found : c , 44.62 ; h , 4.85 ; n , 25.75 .
kinetic experiments were performed at 37 c using a standard 
 uv  visible spectrophotometer .
reactions were initiated by addition 
 of substrate to a preheated cuvette containing the buffer .
analyte 
 concentration was measured in 100 m 0.1 m phosphate buffer , 
 ph 7.4 , containing 50 m diethylenetriamine pentaacetic acid 
 ( dtpa ) . in each experiment ,
the data were analyzed at the max and the rate was derived by fitting the data to an exponential 
 curve typical for first - order processes .
chemiluminescence detection and quantification of no evolving from 
 the reactions were conducted using a commercial nitric oxide analyzer . 

a ph 7.4 solution of 0.1 m phosphate buffer with 50 m dtpa 
 was sparged with inert gas until a steady detector response was established . 

compound 1a , 1b , or ipa / no was added to 
 a final concentration of 100 m , and the no release profile 
 was followed over time after injection .
the resulting curve was integrated 
 to quantify the amount of no released / mol of compound .
each reaction was allowed to proceed 
 to completion , according to the protocol above , in the absence of 
 purging with inert gas .
we then added 100 l of griess reagent , 
 300 l of sample , and 2.6 ml of deionized water together in 
 a spectrophotometer cuvette .
we incubated the mixture for 30 min at 
 room temperature and prepared a reference sample by mixing 100 l 
 of griess reagent and 2.9 ml of deionized water .
the absorbance of 
 the nitrite - containing sample at 548 nm relative to the reference 
 sample was converted to nitrite concentrations using a calibration 
 curve .
the gas chromatography 
 was performed using an electron capture detector , equipped with a ni 370 mbq source . a packed column
( 2 m  2.0 mm i.d . ) 
 was used with helium as the carrier gas .
the gc operation conditions 
 were as follows : injector and detector temperatures were at 250 c ; 
 oven temperature was programmed from 90 to 200 c at 20 c / min 
 and held at 200 c for 1.1 min ; helium flow was 30 ml / min ; and 
 nitrogen was used as makeup gas at 2 ml / min .
the organic products of the aqueous decomposition of 1a and 1b were analyzed by nmr upon exhaustion of the 
 nitrogenous products in a deuterated phosphate buffer under the conditions 
 listed above .
single - crystal x - ray diffraction data 
 on compounds 2 and 4b were collected using 
 mo k radiation and a bruker apex-2 ccd area detector .
crystals 
 were prepared for data collection by coating with high viscosity microscope 
 oil .
the oil - coated crystal was mounted on a micromesh mount and transferred 
 to the diffractometer .
the structures were solved by direct methods 
 and refined by full - matrix least - squares on f values using the programs found in the shelxtl suite ( bruker , 
 shelxtl v6.10 , 2000 , bruker axs inc . , madison , wi ) .
parameters 
 refined included atomic coordinates and anisotropic thermal parameters 
 for all non - hydrogen atoms .
hydrogen atoms on carbons were included 
 using a riding model ( coordinate shifts of c applied to h atoms ) with 
 the c  h distance set at 0.96  .
complete information on 
 data collection and refinement is available in the supporting information . for compound 2 , 

a 0.256  0.047  0.011 mm crystal was prepared 
 for data collection and a data set collected at 150 k. the crystal 
 was triclinic in space group p1 , with unit 
 cell dimensions of a = 5.429(4 )  , b = 8.743(5 )  , c = 16.342(11 )  ,  

= 96.30(3) ,  = 96.60(3) , and  = 92.33(3). 
 data were 92.5% complete to 23.30  ( 0.90  , 
 the limit of diffraction for this crystal ) with an average redundancy 
 of 1.35 . the final anisotropic full - matrix least - squares refinement 
 on f with 201 variables converged at r1 = 7.72% for the observed data and wr2 = 24.35% for all data . for compound 4b , a 0.258 
  0.184
 0.058 mm crystal was prepared for 
 data collection and a data set collected at 150 k. the crystal was 
 monoclinic in space group c2/c , 
 with unit cell dimensions of a = 18.3109(19 )  , b = 10.8087(9 )  , c = 20.0132(16 ) 
  , and  = 109.785(4). data were 99.6% complete to 
 28.33  ( 0.73  ) with an average redundancy 
 of 4.22 . the final anisotropic full - matrix least - squares refinement 
 on f with 244 variables converged at r1 = 4.54% for the observed data and wr2 = 14.23% for all data .
atomic coordinates for 2 and 4b have been deposited with the cambridge crystallographic 
 data centre ( deposition numbers 1015513 and 1015514 , respectively ) . 

copies of the data can be obtained , free of charge , on application 
 to ccdc , 12 union road , cambridge , cb2 1ez , uk [ fax : + 44(0)-1223 - 336033 
 or e - mail : deposit@ccdc.cam.ac.uk .
 we 
 report the apparently unprecedented direct reaction of nitric oxide 
 ( no ) with amides to generate ions of structure r(c = o)nh  n(o)=no , with examples including r = me ( 1a ) 
 or 3-pyridyl ( 1b ) . 
 the sodium salts of both released 
 no in ph 7.4 buffer , with 37 c half - lives of 13 min . 
 as no - releasing drug candidates , 
 diazeniumdiolated amides would have 
 the advantage of generating only 1 equiv of base on hydrolyzing exhaustively 
 to no , in contrast to their amine counterparts , which generate 2 equiv 
 of base . 
Experimental Section