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Jiande Gu

Publications and source records attributed to Jiande Gu.

18 recordsLinked to original sources
PubMed2006

Understanding electron attachment to the DNA double helix: the thymidine monophosphate-adenine pair in the gas phase and aqueous solution.

Electron attachment to the 2'-deoxythymidine-5'-monophosphate-adenine pairs (5'-dTMPH-A and 5'-dTMP(-)-A) has been investigated at a carefully calibrated level of theory (B3LYP/DZP++) to investigate the electron-accepting properties of thymine (T) in the DNA double helix under physiological conditions. All molecular structures have been fully optimized in vacuo and in solution. The adiabatic electron affinity of 5'-dTMPH-A in the gas phase has been predicted to be 0.67 eV. Solvent effects greatly increase the electron capture ability of 5'-dTMPH-A. In fact, the adiabatic electron affinity increases to 2.04 eV with solvation. The influence of the solvent environment on the electron-attracting properties of 5'-dTMPH-A arises not only from the stabilization of the corresponding radical anion through charge-dipole interactions, but also by changing the distribution of the unpaired electron in the molecular system. The unpaired electron is covalently bound even during vertical attachment, due to the solvent effects. Solvent effects also weaken the pairing interaction in the thymidine monophosphate-adenine complexes. The phosphate deprotonation is found to have a relatively minor influence on the capture of electrons by the 5'-dTMPH-A species in aqueous solution. The electron distributions, natural population analysis, and geometrical features of the models examined illustrate that the influence of the phosphate deprotonation is limited to the phosphate moiety in aqueous solution. Therefore, it is reasonable to expect that electron attachment to nucleotides will be independent of monovalent counterions in the vicinity of the phosphate group in aqueous solution.

Adenine↗
PubMed2006

Electron attachment-induced DNA single strand breaks: C3'-O3' sigma-bond breaking of pyrimidine nucleotides predominates.

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.

Carbon↗
PubMed2006

Molecular basis of the recognition process: hydrogen-bonding patterns in the guanine primary recognition site of ribonuclease T1.

Investigation of the intrinsic H-bonding pattern of the guanine complex with a sizable segment (from Asn43 to Glu46) of the primary recognition site (PRS) in RNase T1 at the B3LYP/6-311G(d,p) level of theory enables the electronic density characteristics of the H-bonding patterns of the guanine-PRS complexes to be identified. The perfect H-bonding pattern in the guanine recognition site is achieved through the guanine complex interactions with the large segment of the PRS. Two significant short H-bonds, O epsilon 1...HN1 and O epsilon 2...HN2, have been identified. The similar short H-bond distances found in the anionic GC- base pair and in this study suggest that the short hydrogen-bond distances may be characteristic of the multiple H-bonded anionic nucleobases. The H-bonding energy distribution, the geometric analysis of the H-bonding pattern, and the electron structure characteristics of the H-bonds in the guanine PRS of RNase T1 all suggest that the O epsilon 1...HN1 and O epsilon 2...HN2 side-chain H-bonds dominate the binding at the guanine recognition site of RNase T1. Also, the geometry evidence, the electron structure characteristics, and the properties of the bond critical points of the H-bonds reveal that the side-chain H-bonding and the main-chain H-bonding are mutually intensifying. Thus the positive cooperativity between Asn43 to Tyr45 and Glu46 is proposed.

Binding Sites↗
PubMed2006

Phosphonylation mechanisms of sarin and acetylcholinesterase: a model DFT study.

Potential energy surfaces for the phosphonylation of sarin and acetylcholinesterase (AChE) have been theoretically studied at the B3LYP/6-311G(d,p) level of theory. The obtained results show that the phosphonylation process involves a two-step addition-elimination mechanism, with the first step (addition process) being the rate-determining step, while by comparison, the ensuing steps are very rapid. Stable trigonal bipyramidal intermediates are formed in the studied pathways. It is also revealed that the catalytic triad of acetylcholinesterase plays the catalytic role in the reaction by speeding up the phosphonylation process, as it does in the acylation reaction of ACh and AChE. The effect of aqueous solvation was accounted for via the polarizable continuum model. It is concluded that the enzymatic reaction here is influenced strongly by the solvent environment.

Acetylcholinesterase↗
PubMed2006

DNA strand breaks induced by near-zero-electronvolt electron attachment to pyrimidine nucleotides.

To elucidate the mechanism of DNA strand breaks by low-energy electrons (LEE), theoretical investigations of the LEE attachment-induced C(5')-O(5') sigma bond breaking of pyrimidine nucleotides (5'-dCMPH and 5'-dTMPH) were performed by using the B3LYP/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 LEE-induced 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 C-O or glycosidic bond breaking, yielding neutral ribose radical fragments and the corresponding phosphoric anions or base anions. The C-O 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(5')-O(5') bond breaking predicted in this work are relevant when the counterions are close enough to the phosphate moiety of DNA.

DNA↗
PubMed2006

Microsolvation effect, hydrogen-bonding pattern, and electron affinity of the uracil-water complexes U-(H2O)n (n = 1, 2, 3).

To achieve a systematic understanding of the influence of microsolvation on the electron accepting behaviors of nucleobases, the reliable theoretical method (B3LYP/DZP++) has been applied to a comprehensive conformational investigation on the uracil-water complexes U-(H(2)O)(n) (n = 1, 2, 3) in both neutral and anionic forms. For the neutral complexes, the conformers of hydration on the O2 of uracil are energetically favored. However, hydration on the O4 atom of uracil is more stable for the radical anions. The electron structure analysis for the H-bonding patterns reveal that the CH...OH(2) type H-bond exists only for di- and trihydrated uracil complexes in which a water dimer or trimer is involved. The electron density structure analysis and the atoms-in-molecules (AIM) analysis for U-(H(2)O)(n) suggest a threshold value of the bond critical point (BCP) density to justify the CH...OH(2) type H-bond; that is, CH...OH(2) could be considered to be a H-bond only when its BCP density value is equal to or larger than 0.010 au. The positive adiabatic electron affinity (AEA) and vertical detachment energy (VDE) values for the uracil-water complexes suggest that these hydrated uracil anions are stable. Moreover, the average AEA and VDE of U-(H(2)O)(n) increase as the number of the hydration waters increases.

Electrons↗
PubMed2006

Near 0 eV electrons attach to nucleotides.

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.

DNA↗
PubMed2006

A model study of interactions between TcAChE peripheral site segment Tyr70Val71 and loop 1 of Fasciculin 2.

The continuous chain of residues (Thr7 to Ala12) of Loop1 of Fas2 (F1) and its interaction with the peripheral binding sites (Tyr70-Val71) of AChE (P1) has been studied. Our results suggest that the flexibility of Loop1 might be caused by either the partially protonated guanidine group of Arg11 under experimental conditions or by the interaction with the negatively charged center of substrates. The binding energy of F1-P1 is predicted to be -16.6 kcal/mol at the B3LYP/6-311G(d,p) level, which is assumed to originate from one isolated O7...HN10 H-bond, one possible O10...HC71 unconventional O...HC type H-bonding, and the improved pi-bonding cooperativity around the peptide group of the AChE segment Tyr70-Val71. The classical Kitaura-Morokuma energy decomposition analysis, the NPA charge analysis, and the AIM analysis consistently reveal that the peptide group in segment P1 is more polarizable, which might play the key role in the interactions between F1 and P1. The PCM solvent effect corrected results reveal decrease of the interaction energy of the considered model. The importance of Thr8 of Fas2 in the P-site binding of AChE is also concluded. Site-directed mutations on either the Fas2 residue of Thr8 or the AChE residue of Tyr70 are expected to alter the binding behavior of the Loop1 of Fas2 with AChE.

Acetylcholinesterase↗
PubMed2005

The 2'-deoxyadenosine-5'-phosphate anion, the analogous radical, and the different hydrogen-abstracted radical anions: molecular structures and effects on DNA damage.

The 2'-deoxyadenosine-5'-phosphate (5'-dAMP) anion and its related radicals have been studied by reliably calibrated theoretical approaches. This study reveals important physical characteristics of 5'-dAMP radical related processes. One-electron oxidation of the 5'-dAMP anion is found on both the phosphoryl group and the adenine base with electron detachment energies close to that of phosphate. Partial removal of electron density from the adenine fragment leads to an extended pi system which includes the amine group of the adenine. Although the radical-centered carbon increases the extent of bonding with its adjacent atoms, it usually weakens the chemical bonds between the atoms at the alpha- and beta-positions. This tendency should be important in predicting the reactivity of the sugar-based radicals. The overall stability sequence of the H-abstracted 5'-dAMP anionic radicals is consistent with the analogous results for the H-abstracted neutral radicals of the adenosine nucleoside: aliphatic radicals > aromatic radicals. The negatively charged phosphoryl group attached to atom C(5)' of the ribose does not change this energetic sequence. All the H-abstraction produced 5'-dAMP radical anions are distonic radical anions. Studies have shown that the charge-radical-separating feature of the distonic radical anions is biologically relevant. This result should be important in understanding the reactive properties of these H-abstraction-produced anion radicals.

Anions↗
PubMed2005

Hydrogen-bonding interactions in the binding of loop 1 of fasciculin 2 to Torpedo californica acetylcholinesterase: a density functional theory study.

In the present study, the interactions of model complexes at the interface between loop1 of fasciculin 2 (Fas2) and acetylcholinesterase (AChE) are theoretically explored. Three interaction models based upon the crystal structure of the complex of Fas2 with AChE from Torpedo californica (PDB code ) were fully optimized at the B3LYP/6-311G(d,p) level of theory. The atoms-in-molecules (AIM) approach was employed to characterize the corresponding noncovalent hydrogen bonds through the densities and the Laplacians of electron densities at the bond critical points. The total interaction energy of loop 1 (Fas2) with AChE is predicted to be -99.4 kcal/mol. It is concluded that the Fas2 residue Thr8, which contributes more than half of the total binding energy, plays the most important role among the three binding sites. The energy decomposition results through the Kitaura-Morokuma scheme suggest that the electrostatic term is the major component of the entire interaction energy. The positive cooperativity effect revealed in the Thr8(F)-related models was confirmed through the geometry characteristics, AIM results, and the energy decomposition analysis.

Acetylcholinesterase↗
PubMed2005

Structural and energetic characterization of a DNA nucleoside pair and its anion: deoxyriboadenosine (dA)-deoxyribothymidine (dT).

The geometries of the DNA nucleoside pairs between 2'-deoxyriboadenosine (dA) and 2'-deoxyribothymidine (dT) and its anion (dAdT-) were fully optimized using carefully calibrated density functional methods. The addition of an electron to dAdT results in remarkable changes to the two hydrogen bonding distances, the H...O distance decreasing by 0.303 angstroms and the N...H distance increasing by 0.229 angstroms. The electron affinity of the dAdT pair was studied to reveal the correct trends of adiabatic electron affinity (EA(ad)) under the influence of the additional components to the individual bases. The consequence of negative charge in terms of structural variations, energetic changes, and charge distribution were explored. The EA(ad) of dAdT is predicted to be positive (0.60 eV), and it exhibits a substantial increase compared with those of the corresponding bases A and T and the nucleic acid base pair AT. The effects of pairing and the addition of the sugar moiety on the EA(ad) are well described as the summation of the individual influences. The influence of the pairing on the EA is comparable to that of the addition of 2-deoxyribose. The excess charge is mainly located on the thyminyl moiety in the anionic dAdT pair. The positive vertical electron affinity (VEA = 0.20 eV) for dAdT suggests that it is able to form a stable anion through electron attachment. A large vertical detachment energy (VDE = 1.14 eV) has been determined for the anionic dAdT nucleoside pair. Therefore, one may expect that the stable anionic dAdT nucleoside pair should be able to undergo the subsequent glycosidic bond cleavage process.

Adenosine↗
PubMed2005

Glycosidic bond cleavage of pyrimidine nucleosides by low-energy electrons: a theoretical rationale.

DNA damage by attachment of low-energy secondary electrons is a very interesting and important mechanism. Electron capture and subsequent base release are thought to be the elementary steps of this mechanism. The process of the N1-glycosidic bond breaking of anion radicals of pyrimidine nucleosides, specifically the 2'-deoxyribothymidine (dT) and 2'-deoxyribocytidine (dC) anions, has been investigated theoretically at the B3LYP/DZP++ level of theory. The release of nucleobases by the attachment of low-energy electrons depends on the formation of a stable anion radical of the nucleoside. The lower bond-breaking activation energy and the higher vertical electron detachment energy for dT enables the heterolytic cleavage of the N1-glycosidic bond. However, with the higher bond-breaking activation energy and the lower vertical electron detachment energy for dC, the release of cytosine might be impractical when the incident electrons have high kinetic energy. Furthermore, the release of cytosine would have a quantum yield much lower than that of dT when the incident electrons have lower kinetic energy. This study also demonstrates the importance of the proton at O5' of 2'-deoxyribose in the base release process. Extending this investigation from dT to dC advances the insight into the mechanism of the N1-glycosidic bond-breaking process. The information from this extensive investigation should be valuable for further experimental studies of cytosine release in irradiated DNA.

DNA Damage↗
PubMed2005

Comprehensive global energy minimum modeling of the sarin-serine adduct.

DFT-based molecular dynamics and quantum chemistry theory approaches are combined to investigate the various conformers of sarin-serine adduct. Twenty different conformers have been located as the local minima on the potential energy surface. They are categorized into five classes based on the relative orientation of sarin moiety. The energy properties of the twenty sarin-serine conformers revealed in the present study suggest that at least four of the conformers (1-1, 4-1, 4-2, and 5-1) are expected to have crucial contributions to the phosphonylation and dealkylation reactions of the sarin-serine adduct at low temperature. Among them, the 1-1 conformer which has both the lowest energy and the highest Boltzman distribution relative probability is expected to be the most important. However, as the temperature rises, the 4-1 conformer plays a more important role than 1-1 in the sarin-serine adductation reactions. Under the relatively high temperatures, the contribution of conformer 5-1 decreases in the phosphonylation and dealkylation reactions while at least eight other conformers (1-2, 1-3, 3-1, 3-4, 3-7, 4-2, 4-3, and 4-4) are expected to have larger contributions in these reactions.

Computer Simulation↗
PubMed2004

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.

Base Pairing↗
PubMed2004

DNA nucleosides and their radical anions: molecular structures and electron affinities.

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.

Anions↗
PubMed2002

Closed-shell molecules that ionize more readily than cesium.

We report a class of molecules with extremely low ionization enthalpies, one member of which has been determined to have a gas-phase ionization energy (onset, 3.51 electron volts) lower than that of the cesium atom (which has the lowest gas-phase ionization energy of the elements) or of any other known closed-shell molecule or neutral transient species reported. The molecules are dimetal complexes with the general formula M2(hpp)4 (where M is Cr, Mo, or W, and hpp is the anion of 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine), structurally characterized in the solid state, spectroscopically characterized in the gas phase, and modeled with theoretical computations. The low-energy ionization of each molecule corresponds to the removal of an electron from the delta bonding orbital of the quadruple metal-metal bond, and a strong interaction of this orbital with a filled orbital on the hpp ligands largely accounts for the low ionization energies.

Journal Article↗
PubMed2002

Molecular docking and 3-D-QSAR studies on the possible antimalarial mechanism of artemisinin analogues.

Artemisinin (Qinghaosu) is a natural constituent found in Artemisia annua L, which is an effective drug against chloroquine-resistant Plasmodium falciparum strains and cerebral malaria. The antimalarial activities of artemisinin and its analogues appear to be mediated by the interactions of the drugs with hemin. In order to understand the antimalarial mechanism and the relationship between the physicochemical properties and the antimalarial activities of artemisinin analogues, we performed molecular docking simulations to probe the interactions of these analogues with hemin, and then performed three-dimensional quantitative structure-activity relationship (3-D-QSAR) studies on the basis of the docking models employing comparative molecular force fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Molecular docking simulations generated probable 'bioactive' conformations of artemisinin analogues and provided a new insight into the antimalarial mechanism. The subsequent partial least squares (PLS) analysis indicates that the calculate binding energies correlate well with the experimental activity values. The CoMFA and CoMSIA models based on the bioactive conformations proved to have good predictive ability and in turn match well with the docking result, which further testified the reliability of the docking model. Combining these results, that is molecular docking and 3-D-QSAR, together, the binding model and activity of new synthesized artemisinin derivatives were well explained.

Antimalarials↗