Electron Attachment to Solvated dGpdG: Effects of Stacking on Base‐Centered and Phosphate‐Centered Valence‐Bound Radical Anions

To explore the nature of electron attachment to guanine‐centered DNA single strands in the presence of a polarizable medium, a theoretical investigation of the DNA oligomer dinucleoside phosphate deoxyguanylyl‐3′,5′‐deoxyguanosine (dGpdG) was performed by using density functional theory. Four different electron‐distribution patterns for the radical anions of dGpdG in aqueous solution have been located as local minima on the potential energy surface. The excess electron is found to reside on the proton of the phosphate group (dGp^H?dG), or on the phosphate group (dGp^.?dG), or on the nucleobase at the 5′ position (dG^.?pdG), or on the nucleobase at the 3′ position (dGpdG^.?), respectively. These four radical anions are all expected to be electronically viable species under the influence of the polarizable medium. The predicted energetics of the radical anions follows the order dGp^.?dG>dG^.?pdG>dGpdG^.?>dGp^H?dG. The base–base stacking pattern in DNA single strands seems unaffected by electron attachment. On the contrary, intrastrand H‐bonding is greatly influenced by electron attachment, especially in the formation of base‐centered radical anions. The intrastrand H‐bonding patterns revealed in this study also suggest that intrastrand proton transfer might be possible between successive guanines due to electron attachment to DNA single strands.     

Low‐Energy‐Barrier Proton Transfer Induced by Electron Attachment to the Guanine⋅⋅⋅Cytosine Base Pair

The photoelectron spectrum of the anion of the guanine ??? cytosine base apair (GC)^.? is recorded for the first time. The observed variation in the spectral peak‐height ratios with the source conditions suggests the presence of two or more anionic isomers. Two maxima of the broad bands in the photoelectron spectrum were measured at about 1.9 and about 2.6 eV. These values are very well reproduced by the vertical detachment energies of the B3LYP/6‐31++G(d,p) calculated low‐energy anionic structures, which are 1) the Watson–Crick base‐pair anion with proton transferred from N1 of guanine to N3 of cytosine, 2) its analogue in which the proton is transferred from N9 of guanine to N7 of guanine, and 3) the global minimum geometry, which is formed from the latter anion by rotation of guanine about the axis approximately defined by C2 of guanine and C4 of cytosine. Furthermore, a minor difference in the stabilities of the two lowest energy anions explains the experimentally observed source (temperature) dependence of the PES spectrum. A rational procedure, based on the chemistry involved in the formation of anionic dimers, which enables the low‐energy anions populated in the photoelectron spectrum to be identified is proposed. In contrast to the alternative combinatorial approach, which in the studied case would lead to carrying out quantum chemical calculations for 2000–2500 structures, the procedure described here reduces the computational problem to only 15 geometries.     

Comprehensive Analysis of DNA Strand Breaks at the Guanosine Site Induced by Low‐Energy Electron Attachment

To elucidate the role of guanosine in DNA strand breaks caused by low‐energy electrons (LEEs), theoretical investigations of the LEE attachment‐induced C? O σ‐bonds and N‐glycosidic bond breaking of 2′‐deoxyguanosine‐3′,5′‐diphosphate (3′,5′‐dGMP) were performed using the B3LYP/DZP++ approach. The results reveal possible reaction pathways in the gas phase and in aqueous solutions. In the gas phase LEEs could attach to the phosphate group adjacent to the guanosine to form a radical anion. However, the small vertical detachment energy (VDE) of the radical anion of guanosine 3′,5′‐diphosphate in the gas phase excludes either C? O bond cleavage or N‐glycosidic bond breaking. In the presence of the polarizable surroundings, the solvent effects dramatically increase the electron affinities of the 3′,5′‐dGDP and the VDE of 3′,5′‐dGDP^?. Furthermore, the solvent–solute interactions greatly reduce the activation barriers of the C? O bond cleavage to 1.06–3.56 kcal mol^?1. These low‐energy barriers ensure that either C_5′? O_5′ or C_3′? O_3′ bond rupture takes place at the guanosine site in DNA single strands. On the other hand, the comparatively high energy barrier of the N‐glycosidic bond rupture implies that this reaction pathway is inferior to C? O bond cleavage. Qualitative agreement was found between the theoretical sequence of the bond breaking reaction pathways in the PCM model and the ratio for the corresponding bond breaks observed in the experiment of LEE‐induced damage in oligonucleotide tetramer CGTA. This concord suggests that the influence of the surroundings in the thin solid film on the LEE‐induced DNA damage resembles that of the solvent.     

Orientational Preference of Long,Multicenter Bonds in Radical Anion Dimers: A Case Study of π‐[TCNB]22− and π‐[TCNP]22−

The similar shape and electronic structure of the radical anions of 1,2,4,5‐tetracyanopyrazine (TCNP) and 1,2,4,5‐tetracyanobenzene (TCNB) suggest a similar relative orientation for their long, multicenter carbon?carbon bond in π‐[TCNP]₂^2? and in π‐[TCNB]₂^2?, in good accord with the Maximin Principle predictions. Instead, the two known structures of π‐[TCNP]₂^2? have a D_2h(θ=0°) and a C₂(θ=30°) orientation (θ being the dihedral angle that determines the rotation of one radical anion relative to the other along the axis that passes through center of the two six‐membered rings). The only known π‐[TCNB]₂^2? structure has a C₂(θ=60°) orientation. The origin of these preferences was investigated for both dimers by computing (at the RASPT2/RASSCF(30,28) level) the variation with θ of the interaction energy (E_int) and the variation of the E_int components. It was found that: 1) a long, multicenter bond exists for all orientations; 2) the E_int(θ) angular dependence is similar in both dimers; 3) for all orientations the electrostatic component dominates the value of E_int(θ), although the dispersion and bonding components also play a relevant role; and 4) the Maximin Principle curve reproduces well the shape of the E_int(θ) curve for isolated dimers, although none of them reproduce the experimental preferences. Only after the (radical anion)^.? ??? cation⁺ interactions are also included in the model aggregate are the experimental data reproduced computationally.     

Enzymatic Synthesis of 7′,5′‐Bicyclo‐DNA Oligonucleotides

The selection of artificial genetic polymers with tailor‐made properties for their application in synthetic biology requires the exploration of new nucleosidic scaffolds that can be used in selection experiments. Herein, we describe the synthesis of a bicyclo‐DNA triphosphate (i.e., 7′,5′‐bc‐TTP) and show its potential to serve for the generation of new xenonucleic acids (XNAs) based on this scaffold. 7′,5′‐bc‐TTP is a good substrate for Therminator DNA polymerase, and up to seven modified units can be incorporated into a growing DNA chain. In addition, this scaffold sustains XNA‐dependent DNA synthesis and potentially also XNA‐dependent XNA synthesis. However, DNA‐dependent XNA synthesis on longer templates is hampered by competitive misincorporation of deoxyadenosine triphosphate (dATP) caused by the slow rate of incorporation of 7′,5′‐bc‐TTP.     

Energies and Spin States of FeS0/−, FeS20/−, Fe2S20/−, Fe3S40/−, and Fe4S40/− Clusters

The structures and energies of the electronic ground states of the FeS^0/?, FeS₂^0/?, Fe₂S₂^0/?, Fe₃S₄^0/?, and Fe₄S₄^0/? neutral and anionic clusters have been computed systematically with nine computational methods in combination with seven basis sets. The computed adiabatic electronic affinities (AEA) have been compared with available experimental data. Most reasonable agreements between theory and experiment have been found for both hybrid B3LYP and B3PW91 functionals in conjugation with 6‐311+G* and QZVP basis sets. Detailed comparisons between the available experimental and computed AEA data at the B3LYP/6‐311+G* level identified the electronic ground state of ⁵Δ for FeS, ⁴Δ for FeS^?, ⁵B₂ for FeS₂, ⁶A₁ for FeS₂^?, ¹A₁ for Fe₂S₂, ⁸A′ for Fe₂S₂^?, ⁵A′′ for Fe₃S₄, ⁶A′′ for Fe₃S₄^?, ¹A₁ for Fe₄S₄, and ¹A₂ for Fe₄S₄^?. In addition, Fe₂S₂, Fe₃S₄, Fe₃S₄^?, Fe₄S₄, and Fe₄S₄^? are antiferromagnetic at the B3LYP/6‐311+G* level. The magnetic properties are discussed on the basis of natural bond orbital analysis.     

3,4‐Dithiaphosphole and 3,3′,4,4′‐Tetrathia‐1,1′‐Biphosphole π‐Conjugated Systems: S Makes the Impact

Conjugated systems based on phospholes and 1,1′‐biphospholes bearing 3,4‐ethylenedithia bridges have been prepared using the Fagan–Nugent route. The mechanism of this organometallic route leading to intermediate zirconacyclopentadienes has been investigated by using theoretical calculations. This study revealed that the oxidative coupling leading to zirconacyclopentadienes is favored over oxidative addition within the S? C≡C bond both thermodynamically and kinetically. The impact of the presence of the S atoms on the optical and electrochemical behavior of the phospholes and 1,1′‐biphospholes has been systematically evaluated both experimentally and theoretically. A comparison with their “all‐carbon” analogues is provided. Of particular interest, this comparative study revealed that the introduction of S atoms has an impact on the electronic properties of phosphole‐based conjugated systems. A decrease of the HOMO–LUMO separation and a stabilization of the LUMO level were observed. These general trends are also observed with 1,1′‐biphospholes exhibiting σ–π conjugation. The P atom of the 3,4‐ethylenedithiaphospholes can be selectively oxidized by S₈ or O₂. These P modifications result in a lowering of the HOMO–LUMO separation as well as an increase of the reduction and oxidation potentials. The S atoms of the 3,4‐ethylenedithia bridge of the 2,5‐phosphole have been oxidized using m‐chloroperoxybenzoic acid. The resulting 3,4‐ethylenesulfoxide oxophosphole was characterized by an X‐ray diffraction study. Experimental and theoretical studies show that this novel chemical manipulation results in an increase of the HOMO–LUMO separation and an important decrease of the LUMO level. The electropolymerization of 2‐thienyl‐capped 3,4‐ethylenedithiathioxophosphole and 1,1′‐biphosphole is reported. The impact of the S substituents on the polymer properties is discussed.     

Synthesis of a DNA Promoter Segment Containing All Four Epigenetic Nucleosides: 5‐Methyl‐, 5‐Hydroxymethyl‐, 5‐Formyl‐, and 5‐Carboxy‐2′‐Deoxycytidine

A 5‐formyl‐2′‐deoxycytidine (fdC) phosphoramidite building block that enables the synthesis of fdC‐containing DNA with excellent purity and yield has been developed. In combination with phosphoramidites for 5‐methyl‐dC, 5‐hydroxymethyl‐dC, and carboxy‐dC, it was possible to prepare a segment of the OCT‐4 promoter that contains all four epigenetic bases. Because of the enormous interest in these new epigenetic bases, the ability to insert all four of them into DNA should be of great value for the scientific community.     

反相离子对色谱法分析3′, 5′反向寡核苷酸

3′,5′反向寡核苷酸是碱基组成和长度完全相同、碱基顺序相反的两个寡核苷酸序列。以三乙胺为离子对试剂,研究了缓冲液浓度(0.025～0.15 mol/L)、pH (5.0～6.8)、柱温(25～45 ℃)、流速(0.3～0.7 mL/min)以及不同初始洗脱强度和洗脱梯度条件下,6个3′,5′反向寡核苷酸模拟样品保留和分离的变化特点。三组反向序列在缓冲液浓度为0.05 mol/L,pH 6.8和流速0.4 mL/min条件下获得最大分离,温度对分离的影响不大,而初始洗脱强度对反向序列的影响远大于洗脱梯度。实验结果表明3′,5′反向寡核苷酸的分离和保留趋势不完全一致,色谱条件的优化应有利于实现样品在柱上的弱保留。研究结果还显示寡核苷酸序列中5′末端的保留强于3′末端。     

Triplet‐State Aromaticity of 4nπ‐Electron Monocycles: Analysis of Bifurcation in the π Contribution to the Electron Localization Function

The π contribution to the electron localization function (ELF) is used to compare 4nπ‐ and (4n+2)π‐electron annulenes, with particular focus on the aromaticity of 4nπ‐electron annulenes in their lowest triplet state. The analysis is performed on the electron density obtained at the level of OLYP density functional theory, as well as at the CCSD and CASSCF ab initio levels. Two criteria for aromaticity of all‐carbon annulenes are set up: the span in the bifurcation values ΔBV(ELF_π) should be small, ideally zero, and the bifurcation value for ring closure of the π basin RCBV(ELF_π) should be high (≥ 0.7). On the basis of these criteria, nearly all 4nπ‐electron annulenes are aromatic in their lowest triplet states, similar to (4n+2)π‐electron annulenes in their singlet ground states. For singlet biradical cyclobutadiene and cyclooctatetraene constrained to D_4h and D_8h symmetry, respectively, the RCBV(ELF_π) at the CASSCF level is lower (0.531 and 0.745) than for benzene (0.853), even though they have equal proportions of α‐ and β‐electrons.     

Dendrimeric Oligo(phenylenevinylene)‐Extended Dithieno[3,2‐b:2′,3′‐d]phospholes—Synthesis,Self‐Organization,and Optical Properties

A boost from the branches : Incorporation of the dithieno[3,2‐b:2′,3′‐d]phosphole system as a core in oligo(phenylenevinylene) dendrimers (an example is shown here) provides materials that exhibit energy‐transfer features relaying incoming photons from the dendrons towards the core, which in turn shows enhanced emission intensity. The optical properties and self‐assembly features of the dendrimers can be impacted by the terminal groups (‐H, ‐CF₃, or ‐NPh₂) employed.

     

Nonsymmetrical Dithienylethenes Bearing Dithieno[3,2‐b:2′,3′‐d]thiophene Units with Photochromic Performance in the Crystalline Phase

Four novel nonsymmetrical photochromic diarylethene compounds containing dithieno[3,2‐b:2′,3′‐d]thiophene units were designed and synthesized to investigate their photochromic properties. All these molecules adopt a photoactive antiparallel conformation in single crystals, as revealed by X‐ray crystallographic analysis, and exhibit excellent photochromism in solution as well as in the crystalline phase.     

Synthesis and Base Pairing Properties of 1′,5′‐Anhydro‐L‐Hexitol Nucleic Acids (L‐HNA)

Oligonucleotides composed of 1′,5′‐anhydro‐arabino‐hexitol nucleosides belonging to the L series (L ‐HNA) were prepared and preliminarily studied as a novel potential base‐pairing system. Synthesis of enantiopure L ‐hexitol nucleotide monomers equipped with a 2′‐(N⁶‐benzoyladenin‐9‐yl) or a 2′‐(thymin‐1‐yl) moiety was carried out by a de novo approach based on a domino reaction as key step. The L oligonucleotide analogues were evaluated in duplex formation with natural complements as well as with unnatural sugar‐modified oligonucleotides. In many cases stable homo‐ and heterochiral associations were found. Besides T_m measurements, detection of heterochiral complexes was unambiguously confirmed by LC‐MS studies. Interestingly, circular dichroism measurements of the most stable duplexes suggested that L ‐HNA form left‐handed helices with both D and L oligonucleotides.     

Global Minimum‐Energy Structure and Spectroscopic Properties of I2.−⋅n H2O Clusters: A Monte Carlo Simulated Annealing Study

The vibrational (IR and Raman) and photoelectron spectral properties of hydrated iodine‐dimer radical‐anion clusters, I₂^.? ? n H₂O (n=1–10), are presented. Several initial guess structures are considered for each size of cluster to locate the global minimum‐energy structure by applying a Monte Carlo simulated annealing procedure including spin–orbit interaction. In the Raman spectrum, hydration reduces the intensity of the I? I stretching band but enhances the intensity of the O? H stretching band of water. Raman spectra of more highly hydrated clusters appear to be simpler than the corresponding IR spectra. Vibrational bands due to simultaneous stretching vibrations of O? H bonds in a cyclic water network are observed for I₂^.? ? n H₂O clusters with n≥3. The vertical detachment energy (VDE) profile shows stepwise saturation that indicates closing of the geometrical shell in the hydrated clusters on addition of every four water molecules. The calculated VDE of finite‐size small hydrated clusters is extrapolated to evaluate the bulk VDE value of I₂^.? in aqueous solution as 7.6 eV at the CCSD(T) level of theory. Structure and spectroscopic properties of these hydrated clusters are compared with those of hydrated clusters of Cl₂^.? and Br₂^.?.     

Steric Control in the π‐Dimerization of Oligothiophene Radical Cations Annelated with Bicyclo[2.2.2]octene Units

A Two series of oligothiophenes 2 (nT) (n=4,5), annelated with bicyclo[2.2.2]octene (BCO) units at both ends, and quaterthiophenes 3 a – c , annelated with various numbers of BCO units at different positions, were newly synthesized to investigate the driving forces of π‐dimerization and the structure–property relationships of the π‐dimers of oligothiophene radical cations. Their radical‐cation salts were prepared through chemical one‐electron oxidation by using nitrosonium hexafluoroantimonate. From variable‐temperature electron spin resonance and electronic absorption measurements, the π‐dimerization capability was found to vary among the members of the 2 (nT)^{+ .} SbF₆^? series and 3 ^{+ .} SbF₆^? series of compounds. To examine these results, density functional theory (DFT) calculations at the M06‐2X/6‐31G(d) level were conducted for the π‐dimers. This level of theory was found to successfully reproduce the previously reported X‐ray structure of ( 2 (3T))₂²⁺ having a bent π‐dimer structure with cis–cis conformations. The absorption bands obtained by time‐dependent DFT calculations for the π‐dimers were in reasonable agreement with the experimental spectra. The attractive and repulsive forces for the π‐dimerization were divided into four factors: 1) SOMO–SOMO interactions, 2) van der Waals forces, 3) solvation, and 4) Coulomb repulsion, and the effects of each factor on the structural differences and chain‐length dependence are discussed in detail.