The Asian tiger mosquito, Aedes albopictus, is a highly successful invasive species that transmits a number of human viral diseases, including dengue and Chikungunya fevers. This species has a large genome with significant population-based size variation. The complete genome sequence was determined for the Foshan strain, an established laboratory colony derived from wild mosquitoes from southeastern China, a region within the historical range of the origin of the species. The genome comprises 1,967 Mb, the largest mosquito genome sequenced to date, and its size results principally from an abundance of repetitive DNA classes. In addition, expansions of the numbers of members in gene families involved in insecticide-resistance mechanisms, diapause, sex determination, immunity, and olfaction also contribute to the larger size. Portions of integrated flavivirus-like genomes support a shared evolutionary history of association of these viruses with their vector. The large genome repertory may contribute to the adaptability and success of Ae. albopictus as an invasive species.

To elucidate the mechanism of DNA strand breaks by low-energy electrons (LEE), theoretical investigations of the LEE attachmentinduced C 5OO5 bond breaking of pyrimidine nucleotides (5-dCMPH and 5-dTMPH) were performed by using the B3LYP͞ DZP؉؉ approach. The results indicate that the pyrimidine nucleotides are able to capture electrons characterized by near-0-eV energy to form electronically stable radical anions in both the gas phase and aqueous solution. The mechanism of the LEEinduced single-strand bond breaking in DNA might involve the attachment of an electron to the bases of DNA and the formation of base-centered radical anions in the first step. Subsequently, these radical anions undergo either COO or glycosidic bond breaking, yielding neutral ribose radical fragments and the corresponding phosphoric anions or base anions. The COO bond cleavage is expected to dominate because of its low activation energy. In aqueous solutions, the significant increases in the electron affinities of pyrimidine nucleotides ensure the formation of electronically more stable radical anions of the nucleotides. The low activation energy barriers for the C 5OO5 bond breaking predicted in this work are relevant when the counterions are close enough to the phosphate moiety of DNA. low-energy electrons attachment DNA strand breaks induced by low-energy electrons (LEE) are of crucial importance because such electrons are produced in significant amounts during ionizing radiation (1). Recently, both the experimental investigations of different DNA fragment samples and theoretical studies on different models have demonstrated that, at very low energies, electrons may induce strand breaks in DNA by means of dissociative electron attachment (2-14). A detailed understanding of this LEEinduced DNA damage is essential for the advancement of global models of cellular radiolysis and for the development of more efficient methods of radiotherapy.Based on experimental observations and theoretical rationales, different DNA strand-breaking mechanisms have been proposed (7,9,11,14). These mechanisms are extremely valuable for understanding the nature of DNA strand breaks by LEE.Experimental and theoretical investigations of the basereleasing process of pyrimidine nucleosides (9, 14) have suggested that at the nascent stage the excess electron resides on the * orbital of pyrimidine in the radical anion, forming an electronically stable radical anion. Subsequently, the glycosidic bond breaks to release the free pyrimidine anions and the 2-deoxyribose radical.Theoretical studies of the sugar-phosphate-sugar moiety were performed by Li, Sevilla, and Sanche (7) and by Simons and coworkers (11). Based on the density functional theory (DFT) calculations of the gas-phase model, Li, Sevilla, and Sanche (7) proposed that the near-0-eV (1 eV ϭ 1.602 ϫ 10 Ϫ19 J) electron may be captured first by the phosphate, forming a phosphatecentered radical anion. The subsequent C 3Ј OO 3Ј or C 5Ј OO 5Ј bond breaking was estimated to have an energy barrier of Ϸ10 kcal͞mol...

5607 2.4. Polarizable Continuum Model 5608 3. Electron Attachment to Nucleic Acid Bases and the DNA Backbone 5608 3.1. Guanine 5608 3.2. Adenine 5609 3.3. Cytosine 5609 3.4. Thymine and Uracil 5610 3.5. 5-Halouracils 5610 3.6. DNA Backbone 5611 3.7. Hydrogen Abstracted Nucleobases 5611 4. Electron Attachment to Microsolvated Bases 5612 4.1. Adenine-(H 2 O) n 5612 4.2. Cytosine-(H 2 O) n 5612 4.3. Thymine-(H 2 O) n 5612 4.4. Uracil-(H 2 O) n 5612 4.5. H-Bonded Nucleic Acid Bases 5612 5. Electron Attachment to Nucleobase Pairs 5615 5.1. Adenine−Thymine/Uracil Pair 5615 5.2. Microhydrated Adenine−Thymine/Uracil Pair 5.3. Guanine−Cytosine Base Pair 5.4. Microhydrated Guanine−Cytosine Pairs 5.5. Other Base Pairs 5.6. Base Pair Binding with Metal Clusters 5.7. Hydrogen-Abstracted Radical Base Pairs 6. Electron Attachment to Nucleosides and Nucleotides 6.1. Nucleosides 6.2. Nucleoside Pairs 6.3. Nucleoside Monophosphates 6.4. Nucleoside Diphosphates 7. Electron Attachment to Single-Strand and Double-Strand Nucleotide Oligomers 7.1. dTpdA and dApdT 7.2. dGpdC and dCpdG 7.3. dGpdG 7.4. dGpdCpdG 7.5. [dGpdC] 2 7.6. dGpdGpdG:dCpdCpdC 8. Electron Attachment Induced Bond Breaking in DNA 8.1. Mechanism of Electron Attachment Induced Bond Breaking in DNA 8.

The deoxyribonucleosides have been studied to determine the properties of combinations of 2-deoxyribose with each of the isolated DNA bases for both neutral and anionic species. We have used a carefully calibrated theoretical method [Chem. Rev. 2002, 102, 231], employing the B3LYP hybrid Hartree-Fock/DFT functional with the DZP++ basis set. Predictions are made of the geometric parameters, adiabatic electron affinities, charge distributions based on natural population analysis, and decomposition enthalpy for the neutral and anionic forms of the four 2'-deoxyribonucleosides in DNA: 2'-deoxyriboadenosine (dA), 2'-deoxyribocytidine (dC), 2'-deoxyriboguanosine (dG), and 2'-deoxyribothymidine (dT). Geometric changes in the anions show that the glycosidic bond exhibits little change with excess charge for the guanosine but significant shortening for the adenosine and for the pyrimidines. The zero-point corrected adiabatic electron affinities in eV for each of the 2'-deoxyribonucleosides are as follows: 0.06, dA; 0.09, dG; 0.33, dC; and 0.44, dT. These values are uniformly greater than those of the corresponding isolated bases (-0.28, A; -0.07, G; 0.03, C; 0.20, T) and the isolated 2-deoxyribose (-0.38) at the same level of theory. The vertical detachment energies of dT and dC are substantial, 0.72 and 0.94 eV, and these anions should be observable. A high VDE, 0.91 eV, is also found for dA but its anion is unlikely to be stable due to the small AEA of 0.06 eV. The high VDE reflects the fact that the molecular structures of the anions and the corresponding neutral species are quite different. Valence character is displayed for the SOMOs of dA, dC, and dT, while some component of diffuse character is visible in the SOMO of dG. Further analysis of electronic changes upon electron attachment include an examination of the NPA charges, which show that in the neutral 2'-deoxyribonucleosides the sum of NPA charges for every base is the same, -0.28 with the sum of 2-deoxyribose charges being positive, +0.28. In the anions, the trend in charge division varies based on the nature of the excess electron in the anions. Thermodynamically, the overall enthalpy change for the reaction of water with the neutral nucleosides to give bases and ribose is approximately zero. The analogous decomposition is exothermic by 8 to 11 kcal mol-1 for the anions, indicating possible challenges for anionic gas-phase nucleoside exploration in the presence of water.

A detailed understanding of DNA strand breaks induced by low energy electrons (LEE) is of crucial importance for the advancement of many areas of molecular biology and medicine. To elucidate the mechanism of DNA strand breaks by LEEs, theoretical investigations of the electron attachment-induced C3'-O3' sigma-bond breaking of the pyrimidine nucleotides have been performed. Calculations of 2'-deoxycytidine-3'-monophosphate and 2'-deoxythymidine-3'-monophosphate in their protonated form (denoted as 3'-dCMPH and 3'-dTMPH) have been carried out with the reliably calibrated B3LYP/DZP++ theoretical approach. Our results demonstrate that the transfer of the negative charge from the pi*-orbital of the radical anion of pyrimidines to the DNA backbone does not pass through the N1-glycosidic bond. Instead, the migration of the excessive negative charge through the atomic orbital overlap between the C6 of pyrimidine and the C3' of ribose most likely represents a pathway that subsequently leads to the strand breaks. The proposed mechanism of the LEE-induced single strand breaks in DNA assumes that the formation of the base-centered radical anions is the first step in this process. Subsequently, these electronically stable radical anions may undergo either C-O bond breaking or N-glycosidic bond rupture. The present investigation of 3'-dCMPH and 3'-dTMPH yields an energy barrier of 6.2-7.1 kcal/mol for the C3'-O3' sigma-bond cleavage. This is much lower than the energy barriers required for the C5'-O5' sigma-bond and the N1-glycosidic bond break. Therefore, we conclude that the C3'-O3' sigma-bond rupture dominates the LEE-induced single strand breaks of DNA.

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To elucidate the mechanism of the nascent stage of DNA strand breakage by low-energy electrons, theoretical investigations of electron attachment to nucleotides have been performed by the reliably calibrated B3LYP/DZP++ approach (Chem. Rev. 2002, 102, 231). The 2'-deoxycytidine-3'-monophosphate (3'-dCMPH) and its phosphate-deprotonated anion (3'-dCMP(-)) have been selected herein as models. This investigation reveals that 3'-dCMPH is able to capture near 0 eV electrons to form a radical anion which has a lower energy than the corresponding neutral species in both the gas phase and aqueous solution. The excess electron density is primarily located on the base of the nucleotide radical anion. The electron detachment energy of this pyrimidine-based radical anion is high enough that subsequent phosphate-sugar C-O sigma bond breaking or glycosidic bond cleavage is feasible. Although the phosphate-centered radical anion of 3'-dCMPH is not stable in the gas phase, it may be stable in aqueous solution. However, an incident electron with kinetic energy less than 4 eV might not be able to effectively produce the phosphate-centered radical anion either in solution or in the gas phase. This research also suggests that the electron affinity of the nucleotides is independent of the counterion in aqueous solution.

High level quantum chemistry calculations have been applied in order to explore the intramolecular proton transfer process in the tautomers of adenine. The presence of hydration water stabilizes the imino form of the tautomers of adenine by approximately 2−3 kcal/mol. Inclusion of the bulk electrostatic interaction lowers the relative energy of AamN(7)H and AamN(7)H·H2O to only approximately 4 kcal/mol above AamN(9)H and AamN(9)H·H2O. Consequentely, AamN(7)H might be present in a relatively large concentration in aqueous solutions and biological systems. The activation free energy for the transition of AamN(9)H·H2O to TS1·H2O and for AimN(9)H·H2O to TS1·H2O are 18.0 and 8.6 kcal/mol, while without water assistance, the free energy differences between AamN(9)H and TS1 as well as AimN(9)H and TS1 are 45.2 and 32.6 kcal/mol, respectively. The activation free energy for the N(7)H form is reduced to 16.1 kcal/mol for the transition of AamN(7)H·H2O to TS2·H2O and is reduced to 9.7 kcal/mol for the transition of AimN(7)H·H2O to TS2·H2O. A lower activation energy barrier suggests that thermodynamics might control the tautomeric equilibrium. The inclusion of quantum mechanical tunneling effects in the calculations dramatically increases the proton transfer rate in adenine. The tunneling rates were evaluated to be 1010 times larger than the classical one for the gas phase and 103−104 times larger than for the classical proton transfer rate for the water-assisted process, suggesting the importance of the tunneling effect in the intramolecular proton transfer in the tautomers of adenine.