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PubMed1992

Molecular and biochemical elucidation of a cellular phenotype characterized by adenine analogue resistance in the presence of high levels of adenine phosphoribosyltransferase activity.

A mouse embryonal carcinoma cell line isolated for resistance to the adenine analogue 2,6-diaminopurine (DAP) was found to have near-wild-type levels of adenine phosphoribosyltransferase (APRT) activity in a cell-free assay. This DAP-resistant (DAPr) cell line, termed H29D1, also exhibited near-wild-type levels of adenine accumulation and the ability to grow in medium containing azaserine and adenine. Growth in this medium requires high levels of intracellular APRT activity. Using the polymerase chain reaction (PCR) and the dideoxy chain termination sequencing technique, an A-->G transition was discovered in exon 3 of the aprt gene in H29D1. This mutation resulted in an Arg-to-Gln change at amino acid 87 of the APRT protein that, in turn, resulted in a decreased affinity for adenine. An increased sensitivity of APRT to inhibition by AMP was observed when comparing H29D1 to P19, the parental cell line. Using a transgene containing the A-->G mutation, we demonstrated that this mutation is responsible for the biochemical and cellular phenotypes observed for the H29D1 cell line. The approach used in this study provides a definitive method for linking a mutation to a specific cellular phenotype.

2-Aminopurine↗
PubMed1990

Measurement of adenine nucleotide levels with an adenine analyser as an index of freshness of porgy.

In a prototype of an adenine analyser, adenosine and adenine nucleotides were derivatized with a fluorescent reagent, bromoacetaldehyde, after separation on a Hitachi gel No. 3012-N column by high-performance liquid chromatography. The previous analyser was improved by using a shorter reaction coil and by introduction of a Hitachi gel No. 3013-N with 5-microns particles of porous polystyrene-divinylbenzene, and applied to estimate the freshness of porgy. Total amounts of ATP, ADP and AMP in an isolated muscle just after death gradually decreased to 60% of the original amount after 5 h, and the ATP content rapidly decreased to 20% after 1 h. A good correlation was found between the levels of total adenine compounds and the energy charge values obtained from nineteen porgies frozen at a prerigour state. On the other hand, there existed no relationship between total adenine levels and the K values, which were indices for estimating freshness of fish. The analyser will be useful to evaluate the freshness of tissues and cells based on the higher contents of total adenine compounds, especially ATP.

Adenine Nucleotides↗
PubMed2005

Acid-base and metal-ion-binding properties of 9-[2-(2-phosphonoethoxy)ethyl]adenine (PEEA), a relative of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA). An exercise on the quantification of isomeric complex equilibria in solution.

The acidity constants of 3-fold protonated 9-[2-(2-phosphonoethoxy)ethyl]adenine, H3(PEEA)+, and of 2-fold protonated (2-phosphonoethoxy)ethane, H2(PEE), and the stability constants of the M(H;PEEA)+, M(PEEA), and M(PEE) complexes with M2+ = Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, or Cd2+ have been determined (potentiometric pH titrations; aqueous solution; 25 degrees C; I = 0.1 M, NaNO3). It is concluded that in the M(H;PEEA)+ species, the proton is at the phosphonate group and the metal ion at the adenine residue. The application of previously determined straight-line plots of log K(M(R-PO3))M versus pK(H(R-PO3))H for simple phosph(on)ate ligands, R-PO3(2-), where R represents a residue that does not affect metal-ion binding, proves that the M(PEEA) complexes of Co2+, Ni2+, Cu2+, Zn2+, and Cd2+ as well as the M(PEE) complexes of Co2+, Cu2+, and Zn2+ have larger stabilities than is expected for a sole phosphonate coordination of M2+. For the M2+ complexes without an enhanced stability (e.g., Mg2+ or Mn2+), it is concluded that M2+ binds in a monodentate fashion to the phosphonate group of the two ligands. Combination of all of the results allows the following conclusions: (i) The increased stability of the Co(PEE), Cu(PEE), Zn(PEE), and Co(PEEA) complexes is due to the formation of six-membered chelates involving the ether-oxygen atom of the aliphatic residue (-CH2-O-CH2CH2-PO3(2-)) of the ligands with formation degrees of about 15-30%. (ii) Cd(PEEA) forms a macrochelate with N7 of the adenine residue (formation degree about 30%); Ni(PEEA) has similar properties. (iii) With Zn(PEEA), both mentioned types of chelates are observed, that is, Zn(PEEA)(cl/O) and Zn(PEEA)(cl/N7), with formation degrees of about 13 and 41%, respectively; the remaining 46% is due to the "open" isomer Zn(PEEA)(op) in which the metal ion binds only to the PO3(2-) group. (iv) Most remarkable is Cu(PEEA) because a fourth isomer, Cu(PEEA)(cl/O/N3), is formed that contains a six-membered ring involving the ether oxygen next to the phosphonate group and also a seven-membered ring involving N3 of the adenine residue with a very significant formation degree of about 50%. Hence, PEEA(2-) is a truly ambivalent ligand, its properties being strongly dependent on the kind of metal ion involved. Comparisons with M2+ complexes formed by the dianions of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) and related ligands reveal that five-membered chelates involving an ether-oxygen atom are considerably more stable than the corresponding six-membered ones. This observation offers an explanation of why PMEA is a nucleotide analogue with excellent antiviral properties and PEEA is not.

Adenine↗
PubMed1975

Synthesis of 8-(3'-deoxy-alpha-D-threo-pentofuranosyl) adenine and 9-(3'-deoxy-alpha-D-threo-pentofuranosyl) adenine.

3-Deoxy-2,5-di-O-p-nitrobenzoyl-alpha-D-threo-entofuranosyl bromide (1) reacted with mercuric cyanide to give 2,5-anhydro-4-deoxy-D-lyxo-hexononitrile (2) which upon acid hydrolysis of the CN group gave acid 3. Saponification of the protecting groups gave 2,5-anhydro-4-deoxy-D-lyxo-hexonic acid (4) which reacted with 4,5,6-triaminopyrimidine forming an amide (5) that was pyrolized to give 8-(3'-deoxy-alpha-D-threo-pentofuranosyl) adenine (6). Reaction of bromide 1 with 6-(benzamido) chloromercuriopurine followed by saponification yielded 9-(3'-deoxy-alpha-D-threo-pentofuranosyl)adenine(8). 8-(beta-D-Ribofuranosyl)adenine, 8-(beta-D-arabinofuranosyl)adenine, and 8-(3'-deoxy-beta-D-erythro-pentofuranosyl)adenine, as well as compound 6, showed no antimalarial activity.

Adenine↗
PubMed2002

Acidity of adenine and adenine derivatives and biological implications. A computational and experimental gas-phase study.

The gas-phase acidities of adenine, 9-ethyladenine, and 3-methyladenine have been investigated for the first time, using computational and experimental methods to provide an understanding of the intrinsic reactivity of adenine. Adenine is found to have two acidic sites, with the N9 site being 19 kcal mol(-1) more acidic than the N10 site; the bracketed acidities are 333 +/- 2 and 352 +/- 4 kcal mol(-1), respectively. Because measurement of the less acidic site can be problematic, we benchmarked the adenine N10 measurement by bracketing the acidity of 9-ethyladenine, which has the N9 site blocked and allows for exclusive measurement of the N10 site. The acidity of 9-ethyladenine brackets to 352 +/- 4 kcal mol(-1), comparable to that of the N10 site of the parent adenine. Calculations and experiments with 3-methyladenine, a harmful mutagenic nucleobase, uncovered the surprising result that the most commonly written tautomer of 3-methyladenine is not the most stable in the gas phase. We have found that the most stable tautomer is the "N10 tautomer" 10, as opposed to the imine tautomer 3. The bracketed acidity of 10 is 347 +/- 4 kcal mol(-1). Since 10 is not a viable species in DNA, 3 is a likely tautomer; calculations indicate that this form has an extremely high acidity (320-323 kcal mol(-1)). The biological implications of these results, particularly with respect to enzymes that cleave alkylated bases from DNA, are discussed.

Adenine↗
PubMed2004

Structural basis for removal of adenine mispaired with 8-oxoguanine by MutY adenine DNA glycosylase.

The genomes of aerobic organisms suffer chronic oxidation of guanine to the genotoxic product 8-oxoguanine (oxoG). Replicative DNA polymerases misread oxoG residues and insert adenine instead of cytosine opposite the oxidized base. Both bases in the resulting A*oxoG mispair are mutagenic lesions, and both must undergo base-specific replacement to restore the original C*G pair. Doing so represents a formidable challenge to the DNA repair machinery, because adenine makes up roughly 25% of the bases in most genomes. The evolutionarily conserved enzyme adenine DNA glycosylase (called MutY in bacteria and hMYH in humans) initiates repair of A*oxoG to C*G by removing the inappropriately paired adenine base from the DNA backbone. A central issue concerning MutY function is the mechanism by which A*oxoG mispairs are targeted among the vast excess of A*T pairs. Here we report the use of disulphide crosslinking to obtain high-resolution crystal structures of MutY-DNA lesion-recognition complexes. These structures reveal the basis for recognizing both lesions in the A*oxoG pair and for catalysing removal of the adenine base.

Adenine↗
PubMed1980

Adenine consumption in stored citrate-phosphate-dextrose-adenine blood.

Plasma adenine concentration was measured in five units of citrate-phosphate-dextrose-adenine (0.25 mmol/l adenine) whole blood during storage at +4 degrees C. The adenine levels decreased to 50% in 9-10 days and to approximately 15% in 3 weeks. In spite of this rapid consumption of adenine, the adenosine triphosphate levels were well maintained: almost 100% after 3 weeks and 60% after 6 weeks of storage.

Adenine↗
PubMed2002

Adenine phosphoribosyltransferase isoforms of Arabidopsis and their potential contributions to adenine and cytokinin metabolism.

Adenine phosphoribosyltransferase (APT; EC 2.4.2.7) is a constitutively expressed enzyme involved in the one-step salvage of adenine to AMP. The Arabidopsis thaliana genome contains five sequences annotated as encoding APT or APT-like enzymes. Three of these have now been cloned, over-expressed and compared using kinetic analyses. At a cytosolic pH, all bind adenine efficiently based on their Km values (0.8-2.6 &mgr;M), although APT1 metabolizes adenine at a rate 31-53 times faster than APT2 and APT3, respectively. Since APT also has a possible role in the interconversion of cytokinin bases to nucleotides, we characterized the activity of each isoform on zeatin, isopentenyladenine and benzyladenine. Based on their Km values, APT2 and APT3 had much higher affinities than APT1 for all three cytokinins (15-440 &mgr;M for APT2 and 3 vs. 1.8-2.5 mM for APT1); conversely the Vmax values for APT2 and APT3 on these CK substrates showed the opposite trend, being 4- to 19-fold lower than those of APT1. Anti-peptide antibodies for APT1, APT2, and APT3 were prepared and used to examine the subcellular localization of each isoform. Based on these results, APT1 and APT3 appear to be cytosolic, while the localization of APT2 was inconclusive although sequence analysis implies that APT2 is also cytosolic. Each isoform was modelled against the crystal structure of APT from Leishmania donovani, and structural differences in substrate specificity-determining domains have been found. The estimated kinetic activities of these APTs suggest that they contribute primarily to adenine recycling, although an involvement in cytokinin interconversion cannot be discounted.

Journal Article↗
PubMed1977

[Behavior of adenine nucleotides in stored blood with addition of adenine and guanosine].

ACD stored blood was substituted with adenine, guanosine or both during usual storage conditions. In weekly intervals concentrations of ATP, ADP and AMP were estimated. From the obtained values it was suggested that the substitutions of adenine and guanosine probably lead to synthesis of the three measured adenine nucleotides. The apparent additive effect of adenine and guanosine upon ATP concentration probably is caused by the simultaneous measurement of GTP and ATP in the used nonspecific method. Under these conditions GTP would have significance for the survival of erythrocytes stored in ACD-AG-medium.

Adenine↗
PubMed1993

Microsomal N-oxygenation of adenine to adenine 1-N-oxide.

During investigations on the N-oxygenation of adenine (1) the enzymatic formation of adenine 1-N-oxide 3 was demonstrated for the first time. The identity of this metabolite was confirmed by its chromatographic behaviour and UV-spectrum recorded after HPLC separation. Adenine 1-N-oxide (3) and similar oxygenated derivatives of adenine were synthesized as reference substances. The enzymatic formation of 3 exhibits the typical characteristics of a reaction catalysed by microsomal mono-oxygenases. In induction experiments, an increase in the rate of formation of 3 after pretreatment with phenobarbital was observed. A participation of those isoenzymes of the cytochrome P-450 enzyme system which can be induced by phenobarbital is assumed.

Adenine↗
PubMed1993

Alkylation of DNA by melphalan with special reference to adenine derivatives and adenine-guanine cross-linking.

Alkylation of DNA by melphalan gave four principal products, derived by mono-alkylation of adenine at N-3 and guanine at N-7, and by cross-linking of adenine N-3 to guanine N-7, or of guanine N-7 to guanine N-7. Adenine-guanine cross-linking was unexpected because the two principal nucleophilic centres, N-7 of guanine and N-3 of adenine, are situated in the 'wide' and 'narrow' grooves of the DNA double helix, respectively. These products could be isolated by their hydrolysis from DNA at neutral pH, followed by chromatography of the hydrolysate in an ion-pair ODS system using a solvent containing tetrabutylammonium hydroxide as ion-pairing reagent; this gave better separation than the previously described method using SP-Sephadex.

Adenine↗
PubMed1975

Endogenous purine metabolism in the conidia of wild type and certain adenine mutants of Neurospora crassa. I. The nature of the reserve pools and pool utilization during adenine starvation.

Conidia of four adenine auxotrophs (ad 9, ad 3B, ad 8 and ad 4) of Neurospora crassa differ in their ability to germinate on adenine-deficient medium. A large percentage of the ad 9 and ad 3B mutant conidia germinate while those of ad 8 and ad 4 mutant do not. No correlation was found between the size of the conidial purine reserves and the conidial ability to germinate. In all the strains the major fraction of the conidial purine reserve pools was inosine. The ad 8 and ad 4 mutants are blocked after IMP formation in the adenine biosynthetic pathway and therefore cannot use the stored inosine for germination. Pool-utilization studies indicated that in all strains investigated some of the purine reserves were lost from the conidia during incubation. In the most readily germinating strain, ad 9, only small amounts of the purine pool were lost from the conidia and a large portion of the reserve pool was used for nucleic acid synthesis. The nature of the purine reserves present in the conidia, and the ability of the strains to prevent loss of the stored purines from the conidia appear to be among the factors influencing the conidial germination of the adenine mutants of N. crassa.

Adenine↗
PubMed1985

Electrochemical and glucose oxidase coenzyme activity of flavin adenine dinucleotide covalently attached to glassy carbon at the adenine amino group.

Flavin adenine dinucleotide (FAD) was covalently attached to an electron-conducting support, i.e., glassy carbon. The support was activated by oxidation to create surface carboxylic acid groups, followed by reaction with a water-soluble carbodiimide. FAD was then attached to the activated support by three different methods: (1) directly; (2) through 6-aminocaproic acid as a spacer; and (3) through ethylenediamine glutaraldehyde as a spacer. Coupling occurred at the FAD adenine amino group, or possibly at a ribityl OH group. Cyclic voltammetry was used to determine Eo' values and FAD loadings. The immobilized FAD also acted as a catalyst for the oxidation of reduced nicotinamide adenine dinucleotide (NADH) in that it reduced overpotential by about 195 mV. When the apoenzyme of glucose oxidase was added to the glassy carbon-FAD or glassy carbon-spacer-FAD preparations, no reconstitution of enzyme activity could be observed. This suggests strongly that the adenine amino group of FAD cannot be modified by attachment of something as large as easily visible solid particles. However, it leaves unanswered the question of larger molecular weight material can be accommodated in the FAD-apoenzyme cleft and retain glucose oxidase activity.

Adsorption↗
PubMed2004

Intramolecular stacking interactions in ternary copper(II) complexes formed by a heteroaromatic amine and 9-[2-(2-phosphonoethoxy)ethyl]adenine, a relative of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine.

The stability constants of the mixed-ligand complexes formed between Cu(Arm)2+, where Arm=2,2'-bipyridine (Bpy) or 1,10-phenanthroline (Phen), and the dianions of 9-[2-(2-phosphonoethoxy)ethyl]adenine (PEEA2-) and (2-phosphonoethoxy)ethane (PEE2-), also known as [2-(2-ethoxy)ethyl]phosphonate, were determined by potentiometric pH titrations in aqueous solution (25 degrees C; I=0.1 M, NaNO3). The ternary Cu(Arm)(PEEA) complexes are considerably more stable than the corresponding Cu(Arm)(R-PO3) species, where R-PO3(2-) represents a phosph(on)ate ligand with a group R that is unable to participate in any kind of interaction within the complexes. The increased stability is attributed to intramolecular stack formation in the Cu(Arm)(PEEA) complexes and also, to a smaller extent, to the formation of 6-membered chelates involving the ether oxygen atom present in the -CH2-O-CH2-CH2-PO3(2-) residue of PEEA2-. This latter interaction is separately quantified by studying the ternary Cu(Arm)(PEE) complexes which can form the 6-membered chelates but where no intramolecular ligand-ligand stacking is possible. Application of these results allows a quantitative analysis of the intramolecular equilibria involving three structurally different Cu(Arm)(PEEA) species; e.g., of the Cu(Bpy)(PEEA) system about 11% exist with the metal ion solely coordinated to the phosphonate group, 4% as a 6-membered chelate involving the ether oxygen atom of the -CH2-O-CH2CH2-PO3(2-) residue, and 85% with an intramolecular stack between the adenine moiety of PEEA2- and the aromatic rings of Bpy. In addition, the Cu(Arm)(PEEA) complexes may be protonated, leading to Cu(Arm)(H;PEEA)+ species for which it is concluded that the proton is located at the phosphonate group and that the complexes are mainly formed (50 and 70%) by a stacking adduct between Cu(Arm)2+ and the adenine residue of H(PEEA)-. Finally, the stacking properties of adenosine 5'-monophosphate (AMP2-), of the dianion of 9-[2-(phophonomethoxy)ethyl]adenine (PMEA2-) and of several of its analogues (=PA2-) are compared in their ternary Cu(Arm)(AMP) and Cu(Arm)(PA) systems. Conclusions regarding the antiviral properties of several acyclic nucleoside phosphonates are shortly discussed.

Adenine↗
PubMed2006

Differences in electrostatic potential around DNA fragments containing adenine and 8-oxo-adenine. An analysis based on regular cylindrical projection.

Changes of electrostatic potential (EP) around the DNA molecule resulting from chemical modifications of nucleotides may play a role in enzymatic recognition of damaged sites. Effects of chemical modifications of nucleotides on the structure of DNA have been characterized through large scale density functional theory computations. Quantum mechanical structural optimizations of DNA fragments with three pairs of nucleotides and accompanying counteractions were performed with a B3LYP exchange-correlation functional and 6-31G(d,p) basis sets. The "intact" DNA fragment contained adenine in the middle layer, while the "damaged" fragment had the adenine replaced with 8-oxo-adenine. The electrostatic potential around these DNA fragments was projected on a cylindrical surface around the double helix. The two-dimensional maps of EP of the intact and damaged DNA fragments were analyzed to identify these modifications of EP that result from the occurrence of 8-oxo-adenine (8oA). It was found that distortions of a phosphate group neighboring 8oA and displacements of the accompanying countercation are clearly reflected in the EP maps.

Adenine↗
PubMed1997

Synthesis of nonhydrolyzable analogues of thiazole-4-carboxamide and benzamide adenine dinucleotide containing fluorine atom at the C2' of adenine nucleoside: induction of K562 differentiation and inosine monophosphate dehydrogenase inhibitory activity.

Thiazole-4-carboxamide adenine dinucleotide (TAD) analogue 7 containing a fluorine atom at the C2' arabino configuration of the adenine nucleoside moiety was found to be a potent inducer of differentiation of K562 erythroid leukemia cells. This finding prompted us to synthesize its hydrolysis-resistant methylenebis(phosphonate) and difluoromethylenebis(phosphonate) analogues 8 and 9, respectively. Since both TAD and benzamide adenine dinucleotide (BAD) are potent inhibitors of inosine monophosphate dehydrogenase (IMPDH), the corresponding fluorine-substituted methylenebis(phosphonate) analogue 12 of BAD was also synthesized. Thus, 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine (13) was converted in five steps into the corresponding methylenebis(phosphonate) analogue 18. Dehydration of 18 with DCC led to the formation of the bicyclic trisanhydride intermediate 19a, which upon reaction with 2',3'-O-isopropylidenetiazofurin (20) or -benzamide riboside (21) followed by hydrolysis and deprotection afforded the desired methylene-bridged dinucleotides 8 and 12, respectively. The similar displacement of the 5'-mesyl function of 2',3'-O-isopropylidene-5'-O-mesyltiazofurin (24) with the difluoromethylenebis(phosphonic acid) derivative gave the phosphonate 25 which was coupled with 13 to afford 26. The desired difluoromethylenebis(phosphonate) analogue 9 was obtained by deprotection with Dowex 50/H+. This compound as well as beta-CF2-TAD (4) showed improved differentiation-inducing activity over beta-CH2-TAD (3), whereas analogues containing the -CH2-linkage (8 and 12) were inactive.

Adenine Nucleotides↗
PubMed2002

Protonation studies of modified adenine and adenine nucleotides by theoretical calculations and (15)N NMR.

The acid/base character of nucleobases affects phenomena such as self-association, interaction with metal ions, molecular recognition by proteins, and nucleic acid base-pairing. Therefore, the investigation of proton-transfer equilibria of natural and synthetic nucleos(t)ides is of great importance to obtain a deeper understanding of these phenomena. For this purpose, a set of ATP prototypes was investigated using (15)N NMR spectroscopy, and the corresponding adenine bases were investigated by theoretical calculations. (15)N NMR measurements provided not only acidity constants but also information on the protonation site(s) on the adenine ring and regarding the ratio of the singly protonated species in equilibrium. Substituents of different nature and position on the adenine ring did not change the preferred protonation site, which remained N1. However, for 2-thioether-ATP derivatives a mixed population of N1 and N7 singly protonated species was observed. Reduction of basicity of 0.4-1 pK(a) units relative to ATP was also observed for all evaluated ATP derivatives, except for 2-Cl-ATP, for which K(a) was ca. 10,000-fold lower. To explain the substitution-dependent variations in the experimental pK(a) values of the ATP analogues, gas-phase proton affinities (PA), Delta Delta G(hyd), and pK(a) values of the corresponding adenine bases were calculated using quantum mechanical methods. The computed PA and Delta Delta G(hyd) values successfully explained the experimental pK(a) values. A computational procedure for the prediction of accurate pK(a) values was developed using density functional theory and polarizable continuum model calculations. In this procedure, we developed a set of parameters for the polarizable continuum model that was fitted to reproduce experimental pK(a) values of nitrogen heterocycles. This method is proposed for the prediction of pK(a) values and protonation site(s) of purine analogues that have not been synthesized or analyzed.

Adenine↗
PubMed2004

Gas-phase acidity studies of multiple sites of adenine and adenine derivatives.

The acidities of multiple sites in the purine nucleobase adenine (1) and adenine alkyl derivatives 9-ethyladenine (2), 3-methyladenine (3), 1-methyladenine (4), and N,N-dimethyladenine (5) have been investigated for the first time, using computational and experimental methods to provide an understanding of adenine reactivity. We have previously measured two acidic sites on adenine, with the N9 site being 19 kcal mol(-)(1) more acidic than the N10 site (333 +/- 2 versus 352 +/- 4 kcal mol(-)(1), respectively). In this work, we have established that 9-ethyladenine has two sites more acidic than water: the N10 (352 +/- 4 kcal mol(-)(1)) and the C8 (374 +/- 2 kcal mol(-)(1)). We have likewise measured two acidities for 3-methyladenine, the N10 (347 +/- 4 kcal mol(-)(1)) and the C2 (370 +/- 3 kcal mol(-)(1)). For 1-methyladenine and N,N-dimethyladenine, we measure the N9H acidity to be 331 +/- 2 and 333 +/- 2 kcal mol(-)(1), respectively. We believe that the bracketing of only one site for the latter species is a kinetic effect, which we discuss further in the paper. Computationally, we have found the interesting result that some of the vinylic C-H sites in these purine bases are predicted to be much more acidic than water (DeltaH(acid) = 390.7 kcal mol(-)(1)) in the gas phase, on the order of 373 kcal mol(-)(1). The acidic vinylic C-H sites are always adjacent to an N-R group, and this pattern is maintained regardless of whether the site is on the five- or six-membered ring of the purine. Vinylic C-H sites elsewhere on the purine have calculated acidities of about 400 kcal mol(-)(1). The differing acidities are interpreted through electrostatic potential calculations. We also relate our results to the intriguing biochemical decarboxylation of orotate ribose monophosphate, which involves a vinylic anion adjacent to an N-R group; this decarboxylation is the last step in the de novo biosynthesis of pyrimidine nucleotides, and the enzyme that catalyzes the reaction, orotate ribose monophosphate decarboxylase, has been the subject of intense study recently, as its mechanism remains elusive.

Adenine↗