Modeling β-Scission Reactions of Peptide Backbone Alkoxy Radicals:  Backbone C−C Bond Fission

Wood, Geoffrey P. F.; Rauk, A.; Radom, Leo

doi:10.1021/ct050133g

Cited by 7 publications

(19 citation statements)

References 42 publications

(53 reference statements)

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“…Specifically, the U-CBS-QB3 without spin correction [26][27][28][29] correlates best with the W1U without spin correction, the CBS-QB3 with spin correction correlates best with the W1Usc with spin correction, and the ROCBS-QB3 correlates best with the standard W1͑RO͒ calculations. Specifically, the U-CBS-QB3 without spin correction [26][27][28][29] correlates best with the W1U without spin correction, the CBS-QB3 with spin correction correlates best with the W1Usc with spin correction, and the ROCBS-QB3 correlates best with the standard W1͑RO͒ calculations.…”

Section: Correlation Between Methodsmentioning

confidence: 94%

“…In a highly spin-contaminated species such as the cyano radical, this spin correction, −0.009 54E h ϫ⌬͗S 2 ͘, reduces the error in the unrestricted coupled-cluster 22 singles and doubles with perturbative triples [23][24][25] ͓UCCSD͑T͔͒ energy to a value comparable to that for species with little or no spin contamination ͑Fig. [26][27][28][29] The validity of this approach is reexamined in this study. However, in a number of recent studies of species with less severe spin contamination, [26][27][28][29] it has been found that inclusion of the spin correction term can sometimes lead to poorer agreement with experiment or with the results of higher-level theoretical procedures such as W1 or W2.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A restricted-open-shell complete-basis-set model chemistry

Wood

Radom

Petersson

et al. 2006

The Journal of Chemical Physics

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A restricted-open-shell model chemistry based on the complete basis set-quadratic Becke3 (CBS-QB3) model is formulated and denoted ROCBS-QB3. As the name implies, this method uses spin-restricted wave functions, both for the direct calculations of the various components of the electronic energy and for extrapolating the correlation energy to the complete-basis-set limit. These modifications eliminate the need for empirical corrections that are incorporated in standard CBS-QB3 to compensate for spin contamination when spin-unrestricted wave functions are used. We employ an initial test set of 19 severely spin-contaminated species including doublet radicals and both singlet and triplet biradicals. The mean absolute deviation (MAD) from experiment for the new ROCBS-QB3 model (3.6+/-1.5 kJ mol(-1)) is slightly smaller than that of the standard unrestricted CBS-QB3 version (4.8+/-1.5 kJ mol(-1)) and substantially smaller than the MAD for the unrestricted CBS-QB3 before inclusion of the spin correction (16.1+/-1.5 kJ mol(-1)). However, when applied to calculate the heats of formation at 298 K for the moderately spin-contaminated radicals in the G2/97 test set, ROCBS-QB3 does not perform quite as well as the standard unrestricted CBS-QB3, with a MAD from experiment of 3.8+/-1.6 kJ mol(-1) (compared with 2.9+/-1.6 kJ mol(-1) for standard CBS-QB3). ROCBS-QB3 performs marginally better than standard CBS-QB3 for the G2/97 set of ionization energies with a MAD of 4.1+/-0.1 kJ mol(-1) (compared with 4.4+/-0.1 kJ mol(-1)) and electron affinities with a MAD of 3.9+/-0.2 kJ mol(-1) (compared with 4.3+/-0.2 kJ mol(-1)), but the differences in MAD values are comparable to the experimental uncertainties. Our overall conclusion is that ROCBS-QB3 eliminates the spin correction in standard CBS-QB3 with no loss in accuracy.

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Section: Correlation Between Methodsmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

A restricted-open-shell complete-basis-set model chemistry

Wood

Radom

Petersson

et al. 2006

The Journal of Chemical Physics

Self Cite

225

180

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“…[4][5][6][7][8][9][10][11][12] The thermodynamics and kinetics of the b-fragmentation of some alkoxyl radical carrying nitrogen atoms in the b-position have been investigated at a high level of theory. [13,14] However, their orbital interactions both in the starting materials and at transition state (TS) have not been investigated although it is wellknown that stereoelectronic effects may play a major in the reactivity of organic radicals. It is known that the fragmentation requires the TS geometry to exhibit good overlapping between the SOMO and the bonding s CÀY or the antibonding s* CÀY orbitals of the cleaved CÀY bond (Figure 1 a).…”

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confidence: 99%

β‐Fragmentation of Tertiary Alkoxyl Radicals: G3(MP2)‐RAD and Natural Bond Orbital Investigations

Marque¹,

Siri²

2012

ChemPhysChem

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Tertiary alkoxyl radicals are routinely used in radical chemistry, both in polymerization (initiation, curing, cross-linking, grafting reactions) or chemical modification, [1] and in organic synthesis.[2] They are generated either by reduction of t-alkyl hydroperoxides by metals or by thermal or photochemical decomposition of di t-alkyl peroxides, perketals, and peroxyesters. [3] This family of radicals has been used for decades for addition onto olefins or for H-abstraction from various substrates. [1][2][3] The efficiency of these reactions depends on the occurrence of the b-fragmentation reactions which provide new radicals exhibiting quite different reactivities. [1][2][3] The reactivity of alkoxyl radicals has been recently investigated computationally by quantum chemical calculations and DFT methods. [4][5][6][7][8][9][10][11][12] The thermodynamics and kinetics of the b-fragmentation of some alkoxyl radical carrying nitrogen atoms in the b-position have been investigated at a high level of theory. [13,14] However, their orbital interactions both in the starting materials and at transition state (TS) have not been investigated although it is wellknown that stereoelectronic effects may play a major in the reactivity of organic radicals. It is known that the fragmentation requires the TS geometry to exhibit good overlapping between the SOMO and the bonding s CÀY or the antibonding s* CÀY orbitals of the cleaved CÀY bond (Figure 1 a). Such molecular orbital interactions lead to the weakening of the bond, which is observed through both its lengthening and the diminution of its electron population.[15] In a recent work on the application of natural bond orbital (NBO) analysis to the b-fragmentation of alkoxyl radicals, [16] we observed in starting materials 1 c that the expected interactions between the SOMO and the s and/or the s* orbitals did not occur with the experimentally observed CÀOOEt bond cleavage despite that an early TS is observed for such a reaction (reactant-like from the Hammond's postulate).[17] This puzzling result led us to investigate, using the recommended G3(MP2)-RAD method, the b-fragmentation of the CÀY (left pathway 1, Scheme 1) and CÀMe (right pathway 2, Scheme 1) bonds for alkoxyl radicals 1 a-d, both in its thermodynamical aspects [18] (reaction entalphies DH r , and reaction free Gibbs energies, DG r ) and kinetic aspects [19] (activation barriers DG ¼ 6 ), and some of our results are summarised in Table 1. For comparison, thermodynamic data were calculated using G3 MP2B3 methods. [20] To perform the NBO analysis at TS, kinetic parameters were calculated using the UB3LYP/6-31 + G(d,p) DFT method. [21] The DH r 1 , DH r 2 , DG r 1 , and DG r 2 computed by the G3 MP2B3 method differed by less than 1 kJ mol À1 from those computed by the recommended G3 (MP2)-RAD method, and followed the experimental trend. DG 1 ¼ 6 and DG 2 ¼ 6 calculated by DFT method for radical reaction were very close (less than 5 kJ mol À1) to those computed by the recommended G3(MP2)-RAD method, except for the loss...

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“…The good agreement of these two levels of theory was also suggested in a previous study for the analog ␤-scission of the peptide backbone by an alkoxyl radical. 44 As previously found for radical systems, 45 MP2 and B3LYP, respectively, overestimate (by 1-11 kcal mol -1 ) and underestimate (by 4-10 kcal mol -1 ) the barriers against the ␤-radicalinduced N-C ␣ and C ␣ -C bond cleavages. It is interesting to note that the accuracy of the pure DFT functionals, such as HCTH and PBE, is comparable with that of the B3LYP hybrid DFT functional.…”

Section: Computational Detailsmentioning

confidence: 53%

Theoretical examination of competitive β-radical-induced cleavages of N–C_α and C_α–C bonds of peptides

et al. 2015

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Selective cleavages of N-C ␣ and C ␣ -C bonds of ␤-radical tautomers of amino acid residues in radical peptides have been examined theoretically by means of the density functional theory at the M06-2X/6-311++G(d,p) level. The majority of the bond cleavages are homolytic via ␤-scission. Their energy barriers depend largely on the ability of the radical being stabilized in the transition structures and the availability of a mobile proton in the vicinity of the ␤-radical center. The N-C ␣ bond is less favorably cleaved than the C ␣ -C bond (except Ser and Thr) for systems without a mobile proton. It is because, firstly, the homolytic cleavage is less favorable for the more polar N-C ␣ bond than for the less polar C ␣ -C bond. Secondly, a less stable -radical localized on the amide nitrogen atom of the incipient N-terminal fragment is formed for the former, while a more stable radical delocalized in a *(CO)-like orbital of the incipient C-terminal fragment is formed for the latter. In the presence of a mobile proton N-terminal to the ␤-radical center, some degrees of heterolytic cleavage character, as preferred by the polar N-C ␣ bond, are observed. Consequently, its barrier is reduced. If the mobile proton is located at the C-terminal amide oxygen of the ␤-radical center, the C ␣ -C bond cleavage will be significantly suppressed. It is because the radical in the incipient C-terminal fragment becomes more localized as a -radical on the carbon atom of its protonated amide group. With basic amino acid residues, the C ␣ -C bond cleavage can be reactivated. Heterolytic cleavage of the polar N-C ␣ bond can be largely facilitated if a mobile proton N-terminal to the ␤-radical center is available and the radical in the incipient C-terminal fragment is sufficiently stabilized, for instance, by the aromatic side chain of Trp and Tyr. Therefore, cleavages of the N-C ␣ bond induced by the ␤-radical tautomer of Trp and Tyr are often preferred as compared with cleavages of the C ␣ -C bond in peptide radical cations containing mobile protons.Résumé : Nous avons modélisé les clivages sélectifs des liaisons N-C ␣ et C ␣ -C des tautomères ␤-radicalaires de résidus d'acides aminés dans des peptides radicalaires au niveau M06-2X/6-311++G(d,p) de la théorie de la fonctionnelle de la densité. La majorité des clivages de liaison sont homolytiques et se produisent par scission ␤. Leurs barrières énergétiques dépendent fortement de l'aptitude du radical à être stabilisé dans les structures de transition et de la présence d'un proton labile à proximité du centre ␤-radicalaire. Le clivage de liaison N-C ␣ est moins favorable que celui de la liaison C ␣ -C (sauf dans les résidus Ser et Thr) dans les systèmes sans proton labile. Ce phénomène s'explique premièrement par le fait que le clivage homolytique des liaisons N-C ␣ plus polaires est moins favorable que celui des liaisons C ␣ -C moins polaires. Deuxièmement, un radical moins stable, localisé sur l'atome d'azote de l'amide du fragment N-terminal naissant, se forme dans le premier cas, alor...

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Modeling β-Scission Reactions of Peptide Backbone Alkoxy Radicals: Backbone C−C Bond Fission

Cited by 7 publications

References 42 publications

A restricted-open-shell complete-basis-set model chemistry

A restricted-open-shell complete-basis-set model chemistry

β‐Fragmentation of Tertiary Alkoxyl Radicals: G3(MP2)‐RAD and Natural Bond Orbital Investigations

Theoretical examination of competitive β-radical-induced cleavages of N–C_α and C_α–C bonds of peptides

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Modeling β-Scission Reactions of Peptide Backbone Alkoxy Radicals: Backbone C−C Bond Fission

Cited by 7 publications

References 42 publications

A restricted-open-shell complete-basis-set model chemistry

A restricted-open-shell complete-basis-set model chemistry

β‐Fragmentation of Tertiary Alkoxyl Radicals: G3(MP2)‐RAD and Natural Bond Orbital Investigations

Theoretical examination of competitive β-radical-induced cleavages of N–Cα and Cα–C bonds of peptides

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Theoretical examination of competitive β-radical-induced cleavages of N–C_α and C_α–C bonds of peptides