Supramolecular switches based on the guanine-cytosine (GC) Watson-Crick pair: effect of neutral and ionic substituents

We have theoretically analyzed Watson-Crick guanine-cytosine (GC) base pairs in which purine-C8 and/or pyrimidine-C6 positions carry a substituent X = NH(-), NH(2), NH(3) (+) (N series), O(-), OH, or OH(2) (+) (O series), using the generalized gradient approximation (GGA) of density functional theory at the BP86/TZ2P level. The purpose is to study the effects on structure and hydrogen-bond strength if X= H is substituted by an anionic, neutral, or cationic substituent. We found that replacing X = H by a neutral substituent has relatively small effects. Introducing a charged substituent, on the other hand, led to substantial and characteristic changes in hydrogen-bond lengths, strengths, and hydrogen-bonding mechanism. In general, introducing an anionic substituent reduces the hydrogen-bond-donating and increases the hydrogen-bond-accepting capabilities of a DNA base, and vice versa for a cationic substituent. Thus, along both the N and O series of substituents, the geometric shape and bond strength of our DNA base pair can be chemically switched between three states, thus yielding a chemically controlled supramolecular switch. Interestingly, the orbital-interaction component in some of these hydrogen bonds was found to contribute to more than 49 % of the attractive interactions and is thus virtually equal in magnitude to the electrostatic component, which provides the other (somewhat less than) 51 % of the attraction.     

Effects of OH radical addition on proton transfer in the guanine-cytosine base pair

Double proton transfer (PT) reactions in guanine-cytosine OH radical adducts are studied by the hybrid density functional B3LYP approach. Concerted and stepwise proton-transfer processes are explored between N1(H) on guanine (G) and N3 on cytosine (C), and between N4(H) on C and O6 on G. All systems except GC6OH display a concerted mechanism. 8OHGC has the highest dissociation energy and is 1.2 kcal/mol more stable than the nonradical GC base pair. The origin of the interactions are investigated through the estimation of intrinsic acid-basic properties of the *OH-X monomer (X = G or C). Solvent effects play a significant role in reducing the dissociation energy. The reactions including *OH-C adducts have significantly lower PT barriers than both the nonradical GC pair and the *OH-G adducts. All reactions are endothermic, with the GC6OH --> GC6OHPT reaction has the lowest reaction energy (4.6 kcal/mol). In accordance with earlier results, the estimated NBO charges show that the G moiety carries a slight negative charge (and C a corresponding positive one) in each adduct. The formation of a partial ion pair may be a potential factor leading to the PT reactions being thermodynamically unfavored.     

H-bonding patterns in the platinated guanine-cytosine base pair and guanine-cytosine-guanine-cytosine base tetrad: an electron density deformation analysis and AIM study

The atoms in molecule theory (AIM) and electronic structure analysis are applied together to investigate H-bonding patterns in metalated nucleobase complexes. The influence of Pt on the intra GC base pair H-bonding has been found to reduce intra base pair H-bonding of N4(C)...O6(G) in the platinated GC pair and GCGC tetrad. The relaxation of geometry constrains in metalated nucleobases is found to be decisively important in the formation of novel molecular architectures from nucleobases and metal entities. The incorporation of the platinum in the GCGC tetrad benefits the formation of the unique CH...N (H5(C)...N1(G)) hydrogen bond pattern in the tetrad by offering improved geometric constraints rather than through changing the electronic properties around the H5(C) and N1(G) sites. Platination at the N7 of guanine reduces the deprotonation energy considerably.     

Adiabatic electron affinities of the polyhydrated adenine-thymine base pair: a density functional study

Adiabatic electron affinities (AEAs) of the adenine-thymine (AT) base pair surrounded by 5 and 13 water molecules have been studied by density functional theory (DFT). Geometries of neutral AT x nH2O and anionic (AT x nH2O)- complexes (n = 5 and 13) were fully optimized, and vibrational frequency analysis was performed at the B3LYP/6-31+G** level of theory. The optimized structures of the neutral (AT x nH2O) and (AT x nH2O)- complexes were found to be somewhat nonplanar. Some of the water molecules are displaced away from the AT ring plane and linked with one another by hydrogen bonds. The optimized structures of the complexes are found to be in a satisfactory agreement with the observed experimental and molecular dynamics simulation results. In the optimized anionic complexes, the thymine (T) moiety was found to be puckered, whereas the adenine (A) moiety remained almost planar. Natural population analysis (NPA) performed using the B3LYP/6-31+G** method shows that the thymine moiety in the anionic (AT x nH2O)- complexes (n = 5 and 13) has most of the excess electronic charge, i.e., approximately -0.87 and approximately -0.81 (in the unit of magnitude of the electronic charge), respectively. The zero-point energy corrected adiabatic electron affinities of the hydrated AT base pair were found to be positive both for n = 5 and 13 and have the values of 0.97 and 0.92 eV, respectively, which are almost three times the AEA of the AT base pair. The results show that the presence of water molecules appreciably enhances the EA of the base pair.     

Binding of gold clusters with DNA base pairs: a density functional study of neutral and anionic GC-Aun and AT-Aun (n = 4, 8) complexes

Binding of clusters of gold atoms (Au) with the guanine-cytosine (GC) and adenine-thymine (AT) Watson-Crick DNA base pairs was studied using the density functional theory (DFT). Geometries of the neutral GC-Au(n) and AT-Au(n) and the corresponding anionic (GC-Au(n))(-1) and (AT-Au(n))(-1) (n = 4, 8) complexes were fully optimized in different electronic states, that is, singlet and triplet states for the neutral complexes and doublet and quartet states for the anionic complexes, using the B3LYP density functional method. The 6-31+G basis set was used for all atoms except gold. For gold atoms, the Los Alamos effective core potential (ECP) basis set LanL2DZ was employed. Vibrational frequency calculations were performed to ensure that the optimized structures corresponded to potential energy surface minima. The gold clusters around the neutral GC and AT base pairs have a T-shaped structure, which satisfactorily resemble those observed experimentally and in other theoretical studies. However, in anionic GC and AT base pairs, the gold clusters have extended zigzag and T-shaped structures. We found that guanine and adenine have high affinity for Au clusters, with their N3 and N7 sites being preferentially involved in binding with the same. The calculated adiabatic electron affinities (AEAs) of the GC-Au(n)complexes (n = 4, 8) were found to be much larger than those of the isolated base pairs.     

Double proton transfer in the isolated and DNA-embedded guanine-cytosine base pair

The energetics and dynamics of double proton transfer (DPT) is investigated theoretically for the Watson-Crick conformation of the guanine-cytosine (GC) base pair. Using semiempirical density functional theory the isolated and DNA-embedded GC pair is considered. Differences in the energetics and dynamics of DPT thus addresses the question of how relevant studies of isolated base pairs are for the understanding of processes occurring in DNA. Two-dimensional potential energy surfaces involving the transferring hydrogen atoms and the proton donors and acceptors are presented for both systems. The DPT reaction is accompanied by a contraction of the distance between the two bases with virtually identical energetic barriers being 18.8 and 18.7 kcal/mol for the isolated and DNA-embedded system, respectively. However, the transition state for DPT in the DNA-embedded GC pair is offset by 0.1 A to larger N-H separation compared to the isolated GC pair. Using activated ab initio molecular dynamics, DPT is readily observed for the isolated base pair with a minimal amount of 21.4 kcal/mol of initial average kinetic energy along the DPT normal mode vector. On a time scale of approximately 100 fs DPT has occurred and the excess energy is redistributed. For the DNA-embedded GC pair considerably more kinetic energy is required (30.0 kcal/mol) for DPT and the process is completed within one hydrogen vibration. The relevance of studies of isolated base pairs and base pair analogs in regard of reactions or properties involving DNA is discussed.     

Effect of nucleobase sequence on the proton-transfer reaction and stability of the guanine-cytosine base pair radical anion

The formation of base pair radical anions is closely related to many fascinating research fields in biology and chemistry such as radiation damage to DNA and electron transport in DNA. However, the relevant knowledge so far mainly comes from studies on isolated base pair radical anions, and their behavior in the DNA environment is less understood. In this study, we focus on how the nucleobase sequence affects the properties of the guanine-cytosine (GC) base pair radical anion. The energetic barrier and reaction energy for the proton transfer along the N(1)(G)-H···N(3)(C) hydrogen bond and the stability of GC˙(-) (i.e., electron affinity of GC) embedded in different sequences of base-pair trimer were evaluated using density functional theory. The computational results demonstrated that the presence of neighboring base pairs has an important influence on the behavior of GC˙(-) in the gas phase. The excess electron was found to be localized on the embedded GC and the charge leakage to neighboring base pairs was very minor in all of the investigated sequences. Accordingly, the sequence behavior of the proton-transfer reaction and the stability of GC˙(-) is chiefly governed by electrostatic interactions with adjacent base pairs. However, the effect of base stacking, due to its electrostatic nature, is severely screened upon hydration, and thus, the sequence dependence of the properties of GC˙(-) in aqueous environment becomes relatively weak and less than that observed in the gas phase. The effect of geometry relaxation associated with neighboring base pairs as well as the possibility of proton transfer along the N(2)(G)-H···O(2)(C) channel have also been investigated. The implications of the present findings to the electron transport and radiation damage of DNA are discussed.     

A density functional theory study for the hydrogen-bonded nucleic acid base pair: cytosine dimer

Theoretical investigation for the geometric and energetic properties, rotational constants, harmonic vibrational frequencies, and binding energies of nucleic acid base pair, cytosine dimer, are carried out by using the density functional theory method. The dimer structures resulting from both the keto and the enol (cis/trans) tautomers are investigated in the present study. Various isomers are considered to find the stable structures of the cytosine dimer. The planar cytosine dimer, K-K3 with C2h symmetry, resulting from nonplanar keto tautomers, is found to be thermodynamically most stable out of the four different stable isomers and having the highest binding energy value, 19.51 kcal/mol (including basis set superposition error correction). The vibrational frequency analysis also suggests a red shift of 367.97 cm(-1) for the hydrogen-bonding K-K3 symmetric dimer with two hydrogen bond lengths, each of length 1.913 angstroms. Moreover, charge distribution (ChelpG charges), Laplacian electronic density distribution, and the dimerization equilibrium for the most stable dimer, K-K3, have also been investigated using the same method and the basis set.     

Electron affinity of the guanine-cytosine base pair and structural perturbations upon anion formation

The adiabatic electron affinity (AEA) for the Watson-Crick guanine-cytosine (GC) DNA base pair is predicted using a range of density functional methods with double- and triple-zeta plus polarization plus diffuse (DZP++ and TZ2P++) basis sets in an effort to bracket the true electron affinity. The methods used have been calibrated against a comprehensive tabulation of experimental electron affinities (Chem.Rev. 2002, 102, 231). Optimized structures for GC and the GC anion are compared to the neutral and anionic forms of the individual bases as well as Rich's 1976 X-ray structure for sodium guanylyl-3',5'-cytidine nonahydrate, GpC.9H(2)O. Structural distortions and natural population (NPA) charge distributions of the GC anion indicate that the unpaired electron is localized primarily on the cytosine moiety. Unlike treatments using second-order perturbation theory (MP2), density functional theory consistently predicts a substantial positive adiabatic electron affinity for the GC pair (e.g., TZ2P++/B3LYP: +0.48 eV). The stabilization of C(-) via three hydrogen bonds to guanine is sufficient to facilitate adiabatic binding of an electron to GC and is also consistent with the positive experimental electron affinities obtained by photoelectron spectroscopy of cytosine anions incrementally microsolvated with water molecules. The pairing (dissociation) energy for GC(-) (35.6 kcal/mol) is determined with inclusion of electron correlation and shows the anion to have greater thermodynamic stability; the pairing energy for neutral GC (TZ2P++/B3LYP 23.9 kcal/mol) compares favorably to previous MP2/6-31G (23.4 kcal/mol) results and a debated experiment (21.0 kcal/mol).     

Density functional study of neutral and anionic AlO(n) and ScO(n) with high oxygen content

The electronic and geometrical structures of neutral and negatively charged AlO₅, AlO₆, AlO₇, AlO₈, AlO₉, AlO₁₀, AlO₁₁, AlO₁₂, AlO₁₅, AlO₁₆, and AlO₁₈ along with the corresponding series of ScO_n and ScO oxides were investigated using density functional theory with generalized gradient approximation. We found that these species possess geometrically stable isomers for all values of n = 5–12, 15, 16, 18 and are thermodynamically stable for n = 5–7. The species with n = 16 are found to be octa‐dioxides M(η¹‐O₂)₈ while the species with n = 15 and 18 are penta‐ozonides (η²‐O₃)M(η¹‐O₃)₄ and hexa‐ozonides M(η¹‐O₃)₆, respectively. Geometrical configurations of a number of the lowest total energy states of Al and Sc oxides are different. Especially, drastic differences are found for the anion AlO and ScO pairs at n = 9, 10, and 11. The Sc? O bonds are longer than the Al? O bonds by ≈0.2 Å, which, in turn, slightly affects the corresponding interoxygen bond lengths. The charges on metal atoms are close to +2e in both Al series and to +1.5e in both Sc series. As an extra electron is delocalized over ligands in the presence of a large positive charge on the metal atom of the anions, the electron affinity (EA) of the neutrals along with the ionization energies of the anions are large and exceed the EAs of the halogen atoms in a number of cases. © 2011 Wiley Periodicals, Inc. J Comput Chem 2011     

CpNi(diselenolene)] neutral radical complexes: electron paramagnetic resonance and density functional theory investigations

77Se-enriched CpNi(bds) (bds = 1,2-benzenediselenolate), has been synthesized and its g tensor and 77Se hyperfine tensors have been obtained from its frozen solution electron paramagnetic resonance (EPR) spectrum. These parameters are consistent with those calculated by density functional theory (DFT); it is shown that 10% of the spin is localized on each selenium and that the direction associated to the maximum 77Se couplings is aligned along the gmin direction, perpendicular to the Ni(bds) plane. EPR measurements and DFT calculations are also carried out on the 77Se enriched complex CpNi(dsit) as well on the two dithiolene analogues CpNi(bdt) and CpNi(dmit). The optimized structures of the isolated CpNi(bds) and CpNi(bdt) complexes have been used to generate the idealized dimers (bds)NiCp...CpNi(bds) and (bdt)NiCp...CpNi(bdt) characterized by Cp...Cp overlap. The exchange parameters J calculated at the DFT level for these systems are in reasonable accord with the experimental values. The influence of the geometry of the dimer on its magnetic properties is assessed by calculating the variation of J as a function of the relative orientation of the two Ni(diselenolene) or Ni(dithiolene) planes.     

Photoexcitation of dinucleoside radical cations: a time-dependent density functional study

The excited states of dinucleoside phosphates (dGpdG, dApdA, dApdT, TpdA, and dGpdT) in their cationic radical states were studied with time-dependent density functional theory (TD-DFT). The ground-state geometries of all the dinucleoside phosphate cation radicals considered, in their base stacked conformation, were optimized with the B3LYP/6-31G(d) method. Further, to take into account the effect of the aqueous environment surrounding the dinucleoside phosphates, the polarized continuum model (PCM) was considered and the excitation energies were computed by using the TD-B3LYP/6-31G(d) method. From this study, we find that the first transition in all the dinucleoside molecules involves hole transfer from base to base. dG*+pdG and dApdA*+ were found to have substantially lower first transition energies than others with two different DNA bases. Higher energy transitions involve base to sugar as well as base to base hole transfer. The calculated TD-B3LYP/6-31G(d) transition energies are in good agreement with previous calculations with CASSCF/CAS-PT2 level of theory. This TD-DFT work supports the experimental findings that sugar radicals formed upon photoexcitation of G*+ in gamma-irradiated DNA and suggests an explanation for the wavelength dependence found.     

Triplet (pi,pi) reactivity of the guanine-cytosine DNA base pair: benign deactivation versus double tautomerization via intermolecular hydrogen transfer

Ab initio computations (CASSCF/6-31G* supported by CAS-PT2 single-point calculations) are used to study the reactivity of the triplet excited state of the guanine-cytosine DNA base pair. When the triplet excitation is centered on cytosine there is a competition between benign deactivation to the ground state and a hydrogen transfer route that can trigger double tautomerization. The calculated barriers favor the benign deactivation, but this route goes through a singlet/triplet intersystem crossing with small spin-orbit coupling. Therefore, the potentially mutagenic, double tautomerization route cannot be ruled out completely, and the two paths are probably an alternative to the well-known cytidine photodimerization reaction.     

Microhydration of Cs+ ion: a density functional theory study on Cs+-(H2O)n clusters (n=1-10)

Structure, energy enthalpy, and IR frequency of hydrated cesium ion clusters, Cs+-(H2O)n (n=1-10), are reported based on all electron calculations. Calculations have been carried out with a hybrid density functional, namely, Becke's three-parameter nonlocal hybrid exchange-correlation functional B3LYP applying cc-PVDZ correlated basis function for H and O atoms and a split valence 3-21G basis function for Cs atom. Geometry optimizations for all the cesium ion-water clusters have been carried out with several possible initial guess structures following Newton-Raphson procedure leading to many conformers close in energy. The calculated values of binding enthalpy obtained from present density functional based all electron calculations are in good agreement with the available measured data. Binding enthalpy profile of the hydrated clusters shows a saturation behavior indicating geometrical shell closing in hydrated structure. Significant shifts of O-H stretching bands with respect to free water molecule in IR spectra of hydrated clusters are observed in all the hydrated clusters.     

The neutral analogue of Roussin's red salt anion: a density functional study

Density functional calculations on the experimentally unknown neutral analogue of Roussin's red salt anion, namely Fe(2)(NO)(4)S(2), predict ground state structures with diradical character. The presence of a reactive diradical ground state with unpaired electrons for the neutral Fe(2)(NO)(4)S(2) system could explain why it has not yet been synthesized.     

Selective conformer detection of short-lived base pair tautomers: A computational study of the unusual guanine-cytosine pairs using ultrafast resonance Raman spectroscopy

Base pair mismatch has been regarded as the main source of DNA point mutations, where minor short-lived tautomers were usually involved. However, the detection and characterization of these unnatural species pose challenges to existing techniques. Here, by using systematic structural and ultrafast resonance Raman (RR) spectral analysis for the four possible conformers of guanine-cytosine base pairs, the prominent marker Raman bands were identified. We found that the hydrogen bonding vibrational region from 2300 cm⁻¹ to 3700 cm⁻¹ is ideal for the identification of these short live species. The marker bands provide direct evidence for the existence of the tautomer species, thus offering an effective strategy to detect the short-lived minor species. Ultrafast resonance Raman spectroscopy would be a powerful tool to provide direct evidence of critical dynamical details of complex systems involving protonation or tautomerization.     

Electron attachment to the hydrogenated Watson-Crick guanine cytosine base pair (GC+H): conventional and proton-transferred structures

The anionic species resulting from hydride addition to the Watson-Crick guanine-cytosine (GC) DNA base pair are investigated theoretically. Proton-transferred structures of GC hydride, in which proton H1 of guanine or proton H4 of cytosine migrates to the complementary base-pair side, have been studied also. All optimized geometrical structures are confirmed to be minima via vibrational frequency analyses. The lowest energy structure places the additional hydride on the C6 position of cytosine coupled with proton transfer, resulting in the closed-shell anion designated 1T (G(-)C(C6)). Energetically, the major groove side of the GC pair has a greater propensity toward hydride/hydrogen addition than does the minor grove side. The pairing (dissociation) energy and electron-attracting ability of each anionic structure are predicted and compared with those of the neutral GC and the hydrogenated GC base pairs. Anion 8T (G(O6)C(-)) is a water-extracting complex and has the largest dissociation energy. Anion 2 (GC(C4)(-)) and the corresponding open-shell radical GC(C4) have the largest vertical electron detachment energy and adiabatic electron affinity, respectively. From the difference between the dissociation energy and electron-removal ability of the normal GC anion and the most favorable structure of GC hydride, it is clear that one may dissociate the GC anion and maintain the integrity of the GC hydride.     

Hybrid density functional study of the oxidized states of NiFe-hydrogenase

The oxidized states of NiFe-hydrogenase and their activations have been studied using hybrid DFT. For Ni-B, which is activated in seconds, there is good agreement with experiments. The structure has a bridging hydroxide, which can be removed in two ways. In one pathway an outside electron and a proton is added and water removed, while the other pathway does not involve any outside electrons but uses a hydrogen molecule instead. For Ni-A, which can take hours to activate, there appears to be a rather severe discrepancy with experiments. Even though a structure was obtained in good agreement with experiment, with a protonated peroxide side-on bonded to nickel, this is not the lowest-energy structure. Instead, a structure with a bridging, end-on, protonated peroxide is found to be much lower in energy even for the largest model used with nearly 120 atoms. A remaining deficiency in the chemical model is the most likely explanation for the error. An error of the hybrid DFT method is also possible but appears much less likely, since the agreement between hybrid DFT and non-hybrid DFT is very good. The side-on structure of Ni-A is activated by first adding an outside electron and a proton and then cleaving the O–O bond. Altogether, three outside electrons are required to remove the peroxide, which could be a reason for the slow activation of Ni-A.