Experimental and theoretical characterization of the 3,5-didehydrobenzoate anion: a negatively charged meta-benzyne

A negatively charged analogue of meta-benzyne, 3,5-didehydrobenzoate, was synthesized in a Fourier transform ion cyclotron resonance mass spectrometer, and its reactivity was compared to that of the same ion generated previously in a flowing afterglow apparatus and to its positively charged cousin, N-(3,5-didehydrophenyl)-3-fluoropyridinium. 3,5-Didehydrobenzoate was found to react as a nucleophile with electrophilic reagents. In contrast, N-(3,5-didehydrophenyl)-3-fluoropyridinium does not react with the same electrophilic reagents but reacts instead with nucleophilic reagents. Neither ion is able to abstract hydrogen atoms from typical hydrogen atom donors. The absence of any radical reactivity for these meta-benzynes is consistent with predictions that radical reactions of singlet biradicals should be hindered as compared to their monoradical counterparts. High-level calculations predict that the carboxylate moiety does not significantly perturb the singlet-triplet splitting of 3,5-didehydrobenzoate relative to the parent meta-benzyne.     

Reactions of an aromatic σ,σ-biradical with amino acids and dipeptides in the gas phase

Gas-phase reactivity of a positively charged aromatic σ,σ-biradical (N-methyl-6,8-didehydroquinolinium) was examined toward six aliphatic amino acids and 15 dipeptides by using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR) and laser-induced acoustic desorption (LIAD). While previous studies have revealed that H-atom and NH₂ abstractions dominate the reactions of related monoradicals with aliphatic amino acids and small peptides, several additional, unprecedented reaction pathways were observed for the reactions of the biradical. For amino acids, these are 2H-atom abstraction, H₂O abstraction, addition — CO₂, addition — HCOOH, and formation of a stable adduct. The biradical reacts with aliphatic dipeptides similarly as with aliphatic amino acids, but undergoes also one additional reaction pathway, addition/C-terminal amino acid elimination (addition — CO — NHCHR_C). These reactions are initiated by H-atom abstraction by the biradical from the amino acid or peptide, or nucleophilic addition of an NH₂ or a HO group of the amino acid or peptide at the radical site at C-6 in the biradical. Reactions of the unquenched C-8 radical site then yield the products not observed for related monoradicals. The biradical reacts with aromatic dipeptides with an aromatic ring in N-terminus (i.e., Tyr-Leu, Phe-Val, and Phe-Pro) similarly as with aliphatic dipeptides. However, for those aromatic dipeptides that contain an aromatic ring in the C-terminus (i.e., Leu-Tyr and Ala-Phe), one additional pathway, addition/N-terminal amino acid elimination (addition — CO — NHCHR_N), was observed. This reaction is likely initiated by radical addition of the biradical at the aromatic ring in the C-terminus. Related monoradicals add to aromatic amino acids and small peptides, which is followed by Cα-Cβ bond cleavage, resulting in side-chain abstraction by the radical. For biradicals, with one unquenched radical site after the initial addition, the reaction ultimately results in the loss of the N-terminal amino acid. Similar to monoradicals, the C-S bond in amino acids and dipeptides was found to be especially susceptible to biradical attack.     

Radical Reactivity of the Biradical [⋅P(μ-NTer)2P⋅] and Isolation of a Persistent Phosphorus-Cantered Monoradical [⋅P(μ-NTer)2P-Et]

The activation of C−Br bonds in various bromoalkanes by the biradical [⋅P(μ-NTer)₂P⋅] ( 1 ) (Ter=2,6-bis-(2,4,6-trimethylphenyl)-phenyl) is reported, yielding trans-addition products of the type [Br−P(μ-NTer)₂P−R] ( 2 ), so-called 1,3-substituted cyclo-1,3-diphospha-2,4-diazanes. This addition reaction, which represents a new easy approach to asymmetrically substituted cyclo-1,3-diphospha-2,4-diazanes, was investigated mechanistically by different spectroscopic methods (NMR, EPR, IR, Raman); the results suggested a stepwise radical reaction mechanism, as evidenced by the in-situ detection of the phosphorus-centered monoradical [⋅P(μ-NTer)₂P-R].< To provide further evidence for the radical mechanism, [⋅P(μ-NTer)₂P-Et] ( 3Et ⋅) was synthesized directly by reduction of the bromoethane addition product [Br-P(μ-NTer)₂P-Et] ( 2 a ) with magnesium, resulting in the formation of the persistent phosphorus-centered monoradical [⋅P(μ-NTer)₂P-Et], which could be isolated and fully characterized, including single-crystal X-ray diffraction. Comparison of the EPR spectrum of the radical intermediate in the addition reaction with that of the synthesized new [⋅P(μ-NTer)₂P-Et] radical clearly proves the existence of radicals over the course of the reaction of biradical [⋅P(μ-NTer)₂P⋅] ( 1 ) with bromoethane. Extensive DFT and coupled cluster calculations corroborate the experimental data for a radical mechanism in the reaction of biradical [⋅P(μ-NTer)₂P⋅] with EtBr. In the field of hetero-cyclobutane-1,3-diyls, the demonstration of a stepwise radical reaction represents a new aspect and closes the gap between P-centered biradicals and P-centered monoradicals in terms of radical reactivity.     

Reactivity Controlling Factors for an Aromatic Carbon‐Centered σ,σ,σ‐Triradical: The 4,5,8‐Tridehydroisoquinolinium Ion

The chemical properties of the 4,5,8‐tridehydroisoquinolinium ion (doublet ground state) and related mono‐ and biradicals were examined in the gas phase in a dual‐cell Fourier‐transform ion cyclotron resonance (FT‐ICR) mass spectrometer. The triradical abstracted three hydrogen atoms in a consecutive manner from tetrahydrofuran (THF) and cyclohexane molecules; this demonstrates the presence of three reactive radical sites in this molecule. The high (calculated) electron affinity (EA=6.06 eV) at the radical sites makes the triradical more reactive than two related monoradicals, the 5‐ and 8‐dehydroisoquinolinium ions (EA=4.87 and 5.06 eV, respectively), the reactivity of which is controlled predominantly by polar effects. Calculated triradical stabilization energies predict that the most reactive radical site in the triradical is not position C4, as expected based on the high EA of this radical site, but instead position C5. The latter radical site actually destabilizes the 4,8‐biradical moiety, which is singlet coupled. Indeed, experimental reactivity studies show that the radical site at C5 reacts first. This explains why the triradical is not more reactive than the 4‐dehydroisoquinolinium ion because the C5 site is the intrinsically least reactive of the three radical sites due to its low EA. Although both EA and spin–spin coupling play major roles in controlling the overall reactivity of the triradical, spin–spin coupling determines the relative reactivity of the three radical sites.     

Relative Reactivities of Three Isomeric Aromatic Biradicals with a 1,4-Biradical Topology Are Controlled by Polar Effects

Unexpectedly, the 5-dehydroquinoline radical cation was formed in the gas phase from the 5-iodo-8-nitroquinolinium cation upon ion-trap collision-activated dissociation. This reaction involves the cleavage of a nitro group to generate an intermediate monoradical, namely, the 8-dehydro-5-iodoquinolinium cation, followed by rearrangement through abstraction of a hydrogen atom from the protonated nitrogen atom by the radical site. Dissociation of the rearranged radical cation through elimination of an iodine atom generates the 5-dehydroquinoline radical cation. The mechanism was probed by studying isomeric biradicals and performing quantum chemical calculations. The 5-dehydroquinoline radical cation showed greater gas-phase reactivity toward dimethyl disulfide, cyclohexane, and allyl iodide than the isomeric 5,8-didehydroquinolinium cation, which is more reactive than the isomeric 5,8-didehydroisoquinolinium cation studied previously. All three isomers have a 1,4-biradical topology. The order of reactivity is rationalized by the vertical electron affinities of the radical sites of these biradicals instead of their widely differing singlet–triplet splittings.     

Quantum chemical characterization of the vertical electron affinities of didehydroquinolinium and didehydroisoquinolinium cations

Vertical electron affinities (EA) are predicted for the lowest energy singlet states of the 21 didehydroquinolinium cation isomers and the 21 didehydroisoquinolinium cation isomers, as well as the doublet states of the seven dehydroquinolinium cation isomers, the seven dehydroisoquinolinium cation isomers, the seven N-methyldehydroquinolinium cations, and the seven N-methyldehydroisoquinolinium cations, by using density functional theory. For the monoradicals, the calculated EA of the radical site depends only on the distance from the (formally charged) nitrogen atom, and is reduced by 0.14-0.24 eV when the NH+ group is replaced with an NCH3+ group. Nearly all of the calculated EAs for the ortho biradicals are lower (by 0.04-0.72 eV) than those for either of the corresponding monoradicals. For the meta biradicals, the calculated EAs lie either between the EAs of the corresponding monoradicals or higher (by 0.07-0.58 eV), and they are extremely sensitive to the separation (distance) between the two dehydrocarbon atoms. For the biradicals that do not have either an ortho or meta relationship the calculated EAs are all higher (by 0.02-1.93 eV) than those for either of the corresponding monoradicals. The EAs are examined to gain insight into the nature of inductive/field and resonance effects that influence the electrophilicity of the radical site(s), which is a major factor controlling the reactivity of these types of (bi)radicals.     

Study on the heteroatom influence in pyridine-based nitronyl nitroxide biradicals with phenylethynyl spacers on the molecular ground state

Novel pyridine-based nitronyl nitroxide (NIT) biradicals, 3,5-bis[4-(1-oxyl-3-oxo-4,4,5,5-tetramethylimidazolin-2-yl)phenylethynyl)]pyridine (1) and 2,6-bis[4-(1-oxyl-3-oxo-4,4,5,5-tetramethylimidazolin-2-yl)phenylethynyl)]pyridine (2), and monoradicals, 4-(5-bromopyridine-3-ylethynyl)-1-(1-oxyl-3-oxo-4,4,5,5-tetramethylimidazolin-2-yl)benzene (3), 4-trimethylsilylethynyl-1-(1-oxyl-3-oxo-4,4,5,5-tetramethylimidazolin-2-yl)benzene (4), and 4-trimethylsilylethynyl-1-(1-oxyl-3-oxo-4,4,5,5-tetramethylimidazolin-2-yl)pyridine (5), were synthesized and investigated by ESR and UV-vis spectroscopy. The solution EPR measurements of the biradicals gave well-resolved, nine-line spectra with exact half line spacing as compared to monoradicals (giso = 2.0067) with isotropic line spacing /aN/= 7.36 G. This indicates strong, intramolecular exchange coupling (J > 7 x 10(-4) cm(-1); J/aN > 1) of the biradicals with in the limit of EPR. The temperature dependence on the Deltams = +/-2 signal intensity of biradicals follow Curie behavior down to 4 K ascertaining the triplet ground state or its near-degeneracy with the singlet state. UV-vis studies of 1-5 show characteristic differences in the extinctions of n-pi transitions around 600 nm. Both biradicals 1 and 2 were crystallized in monoclinic space groups C2/c and P2(1)/a with the intraradical distances 1.54 and 1.47 nm, respectively. Computational studies of the biradicals 1, 2, and 1,3-bis[4-(1-oxyl-3-oxo-4,4,5,5-tetramethylimidazolin-2-yl)phenylethynyl)]benzene (T) were performed by the AM1/CAS(8,8) method to calculate the singlet-triplet (DeltaEST) energy difference and the spin density distribution. Results show that the position of the pyridyl nitrogen in 1 and 2 in comparison with T does not alter the triplet ground-state spin multiplicities supporting the obtained experimental results.     

Preparation, spectral behaviour and oxidation of some new zinc(II) salicylaldimines containing sterically hindered phenol.

A series of new bis[N-(2,6-di-tert-butyl-1-hyxyphenyl)salicylideneminato]zinc(II) complexes bearing one or two HO- and CH3O-substituents on the salicylaldehyde moiety were prepared, and their spectroscopic properties (IR, electronic, 1H NMR) as well as the ESR spectra of the one-electron oxidation products were examined. The 1H NMR examination of Zn(Lx)2 indicates that, contrary to expectations, the proton resonances of the complexes are shifted to the high-field side compared with those of the free ligands. Oxidation of these compounds with PbO2 results in the formation of mono- and biradical types Zn(II)-stabilized phenoxyls in which there are both anisotropic and alternating line-width trends. Some spectral patterns are typical for weak interacting (J < A) or the case of J approximately A biradicals, in which ESR signal appeared as superimposition of two non-interacting monoradical centers with S = 1/2. ESR studies on biradicals type of Zn(L*x)2 at 300 and 77 K did not show any evidence of strong exchange coupling in these systems. All radical species were characterized by the ESR parameters.     

Effect of meta electron-donating groups on the electronic structure of substituted phenyl nitrenium ions

Density functional theory (UB3LYP/6-31G(d,p)) was used to determine substituent effects on the singlet-triplet-state energy gap for 21 meta-substituted phenylnitrenium ions. It was found that strongly electron-donating substituents stabilize the triplet state relative to the singlet state. With sufficiently strong meta electron donors (e.g., m,m'-diaminophenylnitrenium ion) the triplet is predicted to be the ground state. Analysis of equilibrium geometries, Kohn-Sham orbital distributions, and Mulliken spin densities for the triplet states of this series of nitrenium ions leads to the conclusion that there are two spatially distinct types of low-energy triplet states. Simple arylnitrenium ions such as phenylnitrenium ions as well as those having electron-withdrawing or weakly donating meta substituents have lowest-energy triplet states that are n,pi in nature. That is, one singly occupied molecular orbital is orthogonal to the plane of the phenyl ring and one is coplanar. These n,pi triplets are generally characterized by large ArNH bond angles (ca. 130-132 degrees ) and an NH bond that is perpendicular to the plane of the phenyl ring. In contrast, meta donor arylnitrenium ions have a lowest-energy triplet state best described as pi,pi. That is, both singly occupied molecular orbitals are orthogonal to the aromatic ring. Such pi,pi states are characterized by NH bonds that are coplanar with the phenyl ring and have ArNH bond angles that are more acute (ca. 110-111 degrees ). These triplet nitrenium ions have electronic structures analogous to those of meta-benzoquinodimethane derivatives.     

Reactivity of the 4,5-didehydroisoquinolinium cation

The chemical properties of a 1,8-didehydronaphthalene derivative, the 4,5-didehydroisoquinolinium cation, were examined in the gas phase in a dual-cell Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer. This is an interesting biradical because it has two radical sites in close proximity, yet their coupling is very weak. In fact, the biradical is calculated to have approximately degenerate singlet and triplet states. This biradical was found to exclusively undergo radical reactions, as opposed to other related biradicals with nearby radical sites. The first bond formation occurs at the radical site in the 4-position, followed by that in the 5-position. The proximity of the radical sites leads to reactions that have not been observed for related mono- or biradicals. Interestingly, some ortho-benzynes have been found to yield similar products. Since ortho-benzynes do not react via radical mechanisms, these products must be especially favorable thermodynamically.     

Experimental evidence for the triplet-like spin state appearing in ground-state singlet biradicals as a key feature for generalized ferrimagnetic spin alignment

The authors have previously proposed a theoretical model for exotic spin alignment in organic molecular assemblages: The alternating chain of organic biradicals in a singlet (Sb=0) ground state and monoradicals with S=1/2 has a ferrimagnetic ground state for the whole chain, which has been termed generalized ferrimagnetism. An important feature of the generalized ferrimagnetic spin alignment has been found in the deviation of the expectation value Sb2 of the biradical spin from zero. Even a triplet-like spin state Sb2=2 (Sb=1) has been predicted in the theoretical calculations. In this study, we have found experimental evidence for the pseudo-triplet state appearing in the ground-state singlet biradical of a real open-shell compound. At first, we have demonstrated from theoretical calculations that the singlet biradical has Sb2=2 (Sb=1) in a molecular pair with an S=1 metal ion as well as with the S=1/2 monoradical. The pseudo-triplet state of the biradical affords a singlet state of the whole system of the biradical-metal ion pair, which is readily detectable in experiments for verifying the theoretical prediction. As a model compound for the biradical-metal ion pair, a transition metal complex, [(bnn)(Ni(hfac)2)1.5(H2O)] (1), has been synthesized from a nitronyl nitroxide-based ground-state singlet biradical bnn and Ni(hfac)2. From X-ray crystallographic analyses, the compound contains a molecular pair of bnn and Ni(hfac)2, which serves as a model system under the above theoretical studies. It has been found from the analysis of the temperature dependence of magnetic susceptibility that the bnn-Ni(hfac)2 pair has the singlet (S=0) ground state. The singlet ground state of the pair results from an antiparallel coupling of the pseudo-triplet of the biradical and the S=1 spin on the Ni ion. The pseudo-triplet state in the ground-state singlet biradical has thus been verified experimentally, which is crucially important to realize the generalized ferrimagnetic spin alignment.     

Lamp versus Laser Photolysis of a Bichromophoric Dichloroalkane: Chemical Evidence for the Two-Photon Generation of the 1,5-Diphenylpentanediyl Biradical

Low intensity (lamp) photolysis of 1,5-dichloro-1,5-diphenylpentane (1) leads to the formation of the 1-chloro-1,5-diphenylpentyl radical (7) through C-Cl bond cleavage. Radical 7 leads to the final products through typical free radical reactions. No cyclopentanes are formed under low intensity conditions. In contrast, high intensity laser irradiation leads to C-Cl photocleavage of radical 7 to yield the 1,5-diphenylpentanediyl biradical (11), which results in the formation of isomeric cis- and trans-1,2-diphenylcyclopentanes; the behavior of these biradicals agrees well with that observed when their precursor is 2,6-diphenylcyclohexanone. Two-color two-laser experiments suggest that both singlet and triplet biradicals are formed, even if only the latter are detectable with nanosecond techniques.     

Syntheses, optical and intramolecular magnetic properties of mono- and di-radicals based on nitronyl-nitroxide and oxoverdazyl groups appended to 2,6-bispyrazolylpyridine cores

This paper presents the synthesis of a series of nitronyl-nitroxide (NN), oxoverdazyl (OVZ) based mono-, and bi-radicals attached to 4-phenyl-2,6-bispyrazolylpyridine coupling unit, their optical, electron spin resonance (ESR) spectroscopic studies and computational analysis. The ESR studies revealed that the axial zero-field splitting (zfs) parameter of the NN biradical (|D/hc| = 0.00719 cm(-1)) is larger than the OVZ biradical (|D/hc| = 0.00601 cm(-1)). Additionally both biradicals displayed forbidden half-field transitions (ΔM(s) = ±2; g(av) ~ 4.01) at 170 K demonstrating their triplet nature. The cryogenic ESR measurements of the two biradicals showed a Curie magnetic behaviour of the ΔM(s) = ±2 signal intensities (χ(EPR)) down to 4.2 K. A detailed comparative analysis of the strength of hyperfine coupling, spin density distribution, zfs and the spin-spin exchange coupling (J) of both NN and OVZ based biradicals showed that the ground state spin multiplicity of both biradicals is probably triplet (S = 1) or it is nearly degenerate singlet-triplet states with J(NN)?J(OVZ).     

Benzylic cations with triplet ground states: computational studies of aryl carbenium ions, silylenium ions, nitrenium ions, and oxenium ions substituted with meta pi donors

Density functional theory (B3LYP/6-31G(d,p)) was used to predict the effect of meta substitution on aryl cationic (Ar-X+) species, including aryloxenium ions, arylsilylenium ions, arylnitrenium ions, and arylcarbenium ions. Multireference second-order perturbation theory (CASPT2) calculations were used to benchmark the quantitative accuracy of the DFT calculations for representative systems. Substituting the meta positions on these species with pi donors stabilizes a pi,pi* diradical state analogous to the well-known m-xylylene diradical. Notably, the 3,5-bis(N,N-dimethylamino)benzyl cation is predicted to have a triplet ground state by 1.9 kcal/mol by DFT and to have essentially degenerate singlet-triplet states at the CASPT2(10,9) level of theory. Adding electron-withdrawing CF3 groups to the exocyclic carbon of this meta-disubstituted benzyl cation further increases the predicted singlet-triplet gap in favor of the triplet. Other aryl cationic species substituted with strong pi electron-donating groups in the meta positions are predicted to have low-energy or ground-state triplet states. Systems analogous to the naphthaquinodimethane diradicals are also reported.     

Chemical properties of a para-benzyne

5,8-Didehydroisoquinolinium ion, a para benzyne analogue, was generated in a Fourier transform ion cyclotron resonance mass spectrometer, and its reactivity toward various neutral reagents was examined. A direct comparison of the reaction kinetics of the para benzyne, a meta isomer, and analogous monoradicals, indicates that the para benzyne is a poorer electrophile but a more reactive radical than its meta isomer.     

Intermolecular Photocyclizations of N‐(ω‐Hydroxyalkyl)tetrachlorophthalimide with Alkenes Leading to Medium‐ and Large‐Ring Heterocycles—Reaction Modes and Regio‐ and Stereoselectivity of the 1,n‐Biradicals

A new photocyclization strategy by using intermolecular tandem reactions between N‐(ω‐hydroxyalkyl)‐4,5,6,7‐tetrachlorophthalimides ( 1 , 2 , and 3 ) and a series of acyclic and cyclic alkenes is reported. Electron transfer of the triplet‐excited phthalimide with the alkene and regioselective trapping of the alkene cation radical by the hydroxyl group at the phthalimide side chain gives a triplet 1,n‐biradical, which after intersystem crossing (ISC) leads to regio‐ and diastereoselective synthesis of polycyclic heterocycles with an N,O‐containing medium to large ring. Regio‐ and diastereoselectivity in the cyclizations are clarified by unambiguous steric structure assignments of the products by X‐ray diffraction or extensive 2D NMR measurements. The diastereoselectivity is decided by the stereochemical course of the ISC process of the triplet 1,n‐biradicals. These intermolecular photoreactions also furnish a new strategy to generate triplet 1,n‐biradicals. Therefore, in photoreactions of 1 and 2 with phenylcyclohexene, the unprecedented stereoselective formation of products by intramolecular hydrogen‐atom transfer in the 1,n‐biradical intermediate was found ( 9 and 23 ). These facts provide direct verification to the reaction pathways of the 1,n‐biradicals and give a new insight into the factors deciding reaction‐pathway partitioning and stereoselectivity.     

Factors affecting the selection of products from a photochemically generated singlet biradical

The chemistries of a monoradical of the ultrafast "radical-clock" type and a structurally related singlet biradical, generated by Norrish type II photochemistry, are compared. The monoradical is found to undergo the characteristic ring-opening reaction of its class at about 10(10) s(-1) at room temperature. However, the singlet biradical shows no evidence of the analogous ring-opening reaction. The contrasting chemistry is traced not to a fundamental difference in electronic structure of the two intermediates, but rather to a steric interaction that the biradical alone would have to suffer during the ring opening. Although the magnitude of the steric hindrance is small (estimated 15-20 kJ mol(-1)), it is enough to shut down the reaction, because the biradical has other facile product-forming reactions available.     

Theoretical and experimental investigations on the reactions of positively charged phenyl radicals with aromatic amino acids

The chemical behavior of positively charged phenyl radicals 3-dehydro-N-phenylpyridinium (a), N-(3-dehydro-5-chlorophenyl)pyridinium (b), and N-(3-dehydrophenyl)pyridinium (c) toward L-tyrosine, phenylalanine, and tryptophan was investigated in the gas phase both theoretically by performing molecular orbital calculations and experimentally by using FT/ICR mass spectrometry. All radicals react with phenylalanine and tryptophan nearly at the collision rate. The overall reactivity of the radicals toward tyrosine follows the order a > b > c, which is consistent with the electron affinity (EA) ordering of the radicals. The higher the electrophilicity (or EA) of the radical, the greater the reactivity. As expected, all radicals abstract a hydrogen atom from all of the amino acids. However, the most electrophilic radical a was also found to react with these amino acids via NH2 abstraction. A new reaction observed between radicals a-c and aromatic amino acids is the addition of the radical to the aromatic ring of the amino acid followed by Calpha-Cbeta bond cleavage, which leads to side-chain abstraction by the radical.     

Quantum chemical characterization of the structures, thermochemical properties, and singlet-triplet splittings of didehydroquinolinium and didehydroisoquinolinium ions

Structural and energetic properties are predicted for the 21 didehydroquinolinium ion isomers and 21 didehydroisoquinolinium ion isomers in their lowest-energy singlet and triplet states by using density functional and multireference second-order perturbation theories. Singlet-triplet splittings and biradical stabilization energies are examined to gain insight into the degree of interaction between the biradical centers, with comparison being made to analogous didehydronaphthalenes and didehydropyridines.     

Gas-phase Reactivity of <Emphasis Type="Italic">meta</Emphasis>-Benzyne Analogs Toward Small Oligonucleotides of Differing Lengths

The gas-phase reactivity of two aromatic carbon-centered σ,σ-biradicals (meta-benzyne analogs) and a related monoradical towards small oligonucleotides of differing lengths was investigated in a Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer coupled with laser-induced acoustic desorption (LIAD). The mono- and biradicals were positively charged to allow for manipulation in the mass spectrometer. The oligonucleotides were evaporated into the gas phase as intact neutral molecules by using LIAD. One of the biradicals was found to be unreactive. The reactive biradical reacts with dinucleoside phosphates and trinucleoside diphosphates mainly by addition to a nucleobase moiety followed by cleavage of the glycosidic bond, leading to a nucleobase radical (e.g., base-H) abstraction. In some instances, after the initial cleavage, the unquenched radical site of the biradical abstracts a hydrogen atom from the neutral fragment, which results in a net nucleobase abstraction. In sharp contrast, the related monoradical mainly undergoes facile hydrogen atom abstraction from the sugar moiety. As the size of the oligonucleotides increases, the rate of hydrogen atom abstraction from the sugar moiety by the monoradical was found to increase due to the presence of more hydrogen atom donor sites, and it is the only reaction observed for tetranucleoside triphosphates. Hence, the monoradical only attacks sugar moieties in these substrates. The biradical also shows significant attack at the sugar moiety for tetranucleoside triphosphates. This drastic change in reactivity indicates that the size of the oligonucleotides plays a key role in the outcome of these reactions. This finding is attributed to more compact conformations in the gas phase for the tetranucleoside triphosphates than for the smaller oligonucleotides, which result from stronger stabilizing interactions between the nucleobases.

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