Cytosine Molecules Research Articles

Quantum Mechanical Modeling of Self-Assembly and Photoinduced Electron Transfer in PNA-Based Artificial Living Organisms

In order to support the creation of both artificial living organisms in the USA LANL "Protocell Assembly" project and programmable nano-biorobots in the EU "Programmable Artificial Cell Evolution" project, we used quantum mechanical (QM), density functional theory (DFT), the semiempirical PM3 method, and molecular mechanics (MM) software to investigate various complex photosynthetic systems based on peptide nucleic acid (PNA) in a water environment. Quantum mechanical DFT PBEPBE simulations, including electron correlations, confirm that water molecules that surround all the photosynthetic complex of the LANL protoorganism are main constructing factors and stabilize this system consisting of: PNA fragment attached by covalent bond sensitizer 1,4-bis(N,N-dimethylamino)naphthalene molecule, lipid precursor molecule and fragment of lipid molecules mono layer. The absorption spectrum shift to the red wavelengths in the complex artificial protocell photosynthetic center might be used as the measure of the complexity of this system. The electron pi-pi* transitions in the first and third excited states are from HOMO and HOMO-1 located on the conjugated water molecules and sensitizer 1,4-bis(N,N-dimethylamino)naphthalene molecule to the LUMO of the lipid precursor molecule as calculated using the time dependent (TD) PBEPBE/6-31G model. Electron charge tunneling in the first and third excited states should induce metabolic photodissociation of the lipid precursor molecule because of localization of the transferred electron cloud on the head (waste) of the lipid precursor molecule. TD electron correlation PBEPBE/6-31G calculations show that in the different energies of excitation, the charge transfer tunneling is from sensitizer to lipid precursor and cytosine molecules. One should note that in a water solvent, the electron charge transfer pi-pi* transition in the fifth and sixth excited state is from the HOMO and HOMO-1 located on the sensitizer 1,4-bis(N,N-dimethylamino)naphthalene molecule to the LUMO+2 located on the cytosine-PNA fragment molecule. Investigation results indicate that strong back electron tunneling from the sensitizer 1,4-bis(N,N-dimethylamino)naphthalene molecule to the cytosine molecule in the LANL artificial photosynthetic system exists.

Observation of far-infrared emission from excited cytosine molecules

We report a time-resolved investigation of the resonant absorption of far-infrared radiation and the subsequent vibrational relaxation processes in a sample of polycrystalline cytosine at 4K, using terahertz time-domain spectroscopy. The subpicosecond time resolution achieved in our experiments corresponds to a near single-cycle of far-infrared radiation, and this enables us to observe the damped oscillations of the electric field produced by excited molecules as they decay. Furthermore, we show that the progressive absorption and subsequent emission of far-infrared radiation at the frequency of the corresponding vibrational mode can be followed directly as a function of time by means of time-partitioned Fourier transforms of the transmitted signal.

EPR study of a copper center in a single crystal of cytosine monohydrate

Copper is found incorporated into the crystal structure of cytosine monohydrate grown from aqueous solution of commercially available cytosine. Upon ionizing irradiation, the crystals exhibited the electron paramagnetic resonance (EPR) spectra characteristic of Cu(II) complex. Planar coordination bonding to the cupric ion, having three nitrogen atoms and an oxygen as ligands, is interpreted to bridge two cytosine molecules, replacing the two cytosine–cytosine hydrogen bonds present in pure crystals. The EPR signals are much stronger for crystals grown from the solutions to which small amount of copper powder were added.

Geometry optimization of the cytosine molecules in a cytosine stack using the B3LYP crystal orbital method

The B3LYP DFT crystal orbital method was applied (with helical periodicity) to calculate the total energy per unit cell of a cytosine (C) molecule in a C stack. Applying afterwards the multidimensional metric method in its BFGS form, the geometry of a C molecule was optimized in the stack of DNA B (3.36 Å stacking distance, 36° rotation). For comparison, we optimized also the geometry of a C trimer and pentamer (in DNA B form) using the Gaussian 03 program for the B3LYP molecular calculation and the default method for the geometry optimization. The results of the two completely different calculations agree quite well, which supports our confidence in the results of our C stack calculation. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005

Electron affinities of the radicals derived from cytosine

Theoretical studies have been carried out to investigate the electron affinities (EAs) of five radicals derived from cytosine by removing a hydrogen atom (C(-H)*), using carefully calibrated computational methods. Significant structural differences are predicted between cytosine, its five radicals and the five corresponding anions. The largest bond distance differences between the radical and its analogous anion are 0.05 angstroms. The theoretical EAs (predicted using carefully calibrated methods) for the five cytosine radicals range from 2.22 eV to 3.00 eV. Among these the N-centred radical 2 has the largest adiabatic electron affinity (EA(ad) = 3.00 eV), and the carbon-centred radical 8 has the smallest (2.22 eV). These values are much larger than EA(ad) for the neutral closed-shell cytosine molecule. The largest EA(ad) value predicted for the cytosine radical isomers (C(-H)*) is comparable to those for radicals related to other nucleoside bases. The ordering for the four DNA bases is EA(T(-H)*) = 3.46 > EA(A)-(-H)*) = 3.26 > EA(C(-H)*)= 3.00 > EA(G(-H)*) = 2.99 eV.

Metal deposition onto biomolecular layers on silicon surfaces: a study of interface formation using Raman spectroscopy

In this work the interface formed between the DNA base cytosine and hydrogen passivated Si(1 1 1) substrates is investigated by spectroscopic methods and density functional calculations of optimized adsorbate geometries. The cytosine was thermally evaporated by organic molecular beam deposition onto flat and vicinal H-passivated Si(1 1 1) substrates under ultra-high vacuum (UHV) conditions. In order to take advantage of surface-enhanced Raman scattering at rough metal surfaces, silver was evaporated onto the biomolecular adsorbate. Polarisation-dependent Raman measurements reveal that the cytosine molecules align along the steps on vicinal H–Si(1 1 1) surfaces. The orientation of the molecular plane of the cytosine molecule deduced from the SER spectra can be well reproduced with density functional calculations of the optimized geometries of an adsorbed cytosine molecule at a step edge of H-passivated Si(1 1 1) slab. As the binding energy of cytosine at the substrate step is as large as −0.41 eV, one can conclude that the coverage with silver does not affect the preferential adsorption geometry of the cytosine molecule.

Ab Initio Study of the Prototropic Tautomerism of Cytosine and Guanine and Their Contribution to Spontaneous Point Mutations

High-level quantum-chemical and quantum-dynamics calculations are reported on the tautomerization equilibria and rate constants of isolated and monohydrated cytosine and guanine molecules. The results are used to estimate the fraction of the bases present in the cell during DNA synthesis as the unwanted tautomers that forms irregular base pairs, thus giving rise to a spontaneous GC → AT point mutation. A comparison of the estimated mutation frequencies with the observed frequency in E. coli is used to analyze two proposed mechanisms, differing in the degree of equilibration reached in the tautomerization reaction. It was found that the fraction of the rare tautomer in monohydrated complex of cytosine as well as guanine significantly exceed the amount responsible for the observed values of the GC → AT mutations. In the absence of water the equilibrium concentration of tautomeric forms is relatively large, but the barrier to their formation is high. It is possible that the mechanism in which a high tautomerization barrier keeps the tautomeric transformation far from a state of equilibrium is more likely than a mechanism in which water and/or polymerases produce a low equilibrium concentration of the tautomeric forms.

Density functional theory investigation of the proton hyperfine couplings in thiocytosine oxidation product in the cytosine monohydrate crystal lattice

The spin density distribution and the proton coupling tensors of the neutral thiocytosine electron-loss radical in the crystal matrix of cytosine monohydrate were studied with the use of the density functional theory (DFT) at the B3LYP level. It is shown that the isolated radical approximation makes a poor model for the explanation of all the features observed with the ENDOR spectroscopy. More complex structures, that include one or more neighboring cytosine molecules of the lattice, make more representative systems. The calculations of the geometry optimization with the use of the 6-31G(d) basis set and the single-point calculations with the 6-311+G(2d,p) basis set give the spin distribution and the proton coupling tensors in good accord with the observed values. The calculations confirm the H1 proton transfer from thiocytosine to N3 of the neighboring cytosine molecule along the hydrogen bond. This work represents the first complete DFT analysis of the distant, intermolecular proton coupling tensors for a radical in solids.

The tautomeric equilibria of cytosine studied by NQR spectroscopy and HF, MP2 and DFT calculations

A study was undertaken to check if such parameters as NQR frequencies, quadrupole coupling constants and the asymmetry parameters determined from the 14N NQR spectra can provide sufficient information to infer about the tautomeric form of a compound studied. The influence of the choice of functional on the 14N NQR parameters calculated by ab initio and DFT methods was analysed. Moreover, the influence of the neighbouring molecules on the NQR parameters was checked for the assumed symmetric planar environment of the cytosine molecule in which it is hydrogen-bonded to four other cytosine molecules. Since the use of a finite basis set is always a source of uncertainties in the electric field gradient tensor components, the final calculations for a layer were performed in two different basis sets: middle and extended.

A nucleobase–inorganic hybrid polymer consisting of copper bis(phosphopentamolybdate) and cytosine

A nucleobase–inorganic hybrid polymer built from P2Mo5O23 and Cu(II)–cytosine subunits has been prepared; X-ray crystal structure analysis reveals the cytosine molecules weakly coordinate to copper(II) and connect the P2Mo5O23 subunit through hydrogen bonds to form extended 2D networks with complicated hydrogen bonding modes; a bathochromic shift, compared to free cytosine, can be observed in the fluorescence spectra of the hybrid polymer.

The role of dimer formation in the self-assemblies of DNA base molecules on Cu(111) surfaces: A scanning tunneling microscope study

For the purpose of understanding the self-assembly formation mechanism of DNA base molecules, guanine, adenine, cytosine, and thymine molecules were deposited on Cu(111) surfaces, and were observed using a low-temperature (≈80 K) scanning tunneling microscope (STM). Single-molecular-scale STM images revealed that guanine, adenine, and cytosine molecules can form ordered one- and/or two-dimensional unique structures, but thymine molecules, however, randomly aggregate into small clusters. Semiempirical molecular orbital (MO) calculation indicates that there exists predominantly stable dimer structures for the former three molecules, while such phenomena cannot be observed among the possible thymine dimer and even trimer structures. Based on experimental and theoretical results, we have concluded that specific hydrogen-bonded nucleus formation is a decisive process in the two-dimensional self-assembly formation of DNA base molecules on Cu(111) surfaces.

Interligand interactions affecting specific metal bonding to nucleic acid bases: the tetrakis(μ-trifluoroacetamidato)dirhodium(II)–cytosine system. Crystal structures of [Rh 2(CF 3CONH) 4(cytosine)] and [Rh 2(CF 3CONH) 4(1-methylcytosine) 2]·2H 2O

The reaction of tetrakis(μ-trifluoroacetamidato)dirhodium(II) with cytosine and with 1-methylcytosine in methanolic aqueous solution gave [Rh 2(CF 3CONH) 4(cytosine)] ( 1) and [Rh 2(CF 3CONH) 4(1-methylcytosine) 2]·2H 2O ( 2), respectively, structures of which have been determined by X-ray diffraction. In the cytosine complex 1, a cytosine molecule bridges between the axial positions of the different [Rh 2(CF 3CONH) 4] nuclei, each of which has a crystallographic centre of symmetry at the midpoint of the Rh–Rh bond, through the ring nitrogen N(3) and the exocyclic keto substituent O(2), thereby producing a one-dimensional polymeric adduct. In the 1-methylcytosine complex 2, two 1-methylcytosine molecules occupy the axial positions of the [Rh 2(CF 3CONH) 4] nucleus through N(3), forming a discrete structure. In 1 and 2, the Rh–N(3) axial bonding is accompanied by the formation of two intramolecular hydrogen bonds, one between N(4) of the base and the amidato oxygen and the other between O(2) of the base and the amidato NH. The importance of interligand interactions, associated with the steric metal environment, as factor determining metal binding site on cytosine is emphasised.

Non-expression of HLA-B*5111N is caused by an insertion into the cytosine island at exon 4 creating a frameshift stop codon.

The identification of the "blank" allele HLA-B*5111N, which was detected in German and Czech individuals, is described. In the pedigree analysis this new allele segregates with the serological haplotype HLA-A2; B-; DR4 which is frequent in Czech population. The non-expression of B*5111N is caused by the insertion of an additional cytosine molecule at the cytosine island between the nucleotides 621-626 (codons 183-185, first three codons of exon 4) leading to a frame shift that creates a stop codon at codon 196. This insertion may be explained either by conversion with the pseudogene HLA-J or by slipped-strand mispairing. In order not to overlook the presence of alleles with altered expression in case of hematopoietic stem cell transplantation, both serological and DNA-based typing should be performed (Note).

ENDOR study of the chlorinated thiocytosine radical in a crystal matrix

Interaction of protons with the unpaired electron in the σ2σ*1 three-electron S∴Cl bond has been investigated by electron nuclear double resonance (ENDOR) spectroscopy. The S∴Cl bond in the chlorinated thiocytosine radical, imbedded in the crystal lattice of cytosine hydrochloride, interacts significantly with at least seven protons. Five of these interactions have been analyzed. From the nature of the coupling tensors, it is concluded that three couplings are due to protons being constituents of the chlorine–thiocytosine radical, and the remaining two are due to protons belonging to neighboring cytosine molecules. The nature of the dipolar component of the coupling tensors is not consistent with the location of the entire electron spin density in the S∴Cl bond. From isotropic as well as anisotropic hyperfine coupling tensor components, it is concluded that the unpaired electron is somewhat delocalized over the radical, with a major portion being concentrated in the C(2)–S–Cl region but with a significant fraction occupying a π* molecular orbital extending over the cytosine ring atoms. Density functional theory molecular orbital calculations support such a kind of spin distribution. The data also suggest that the radical remains protonated at both the N(1) and N(3) positions.

Interligand interactions affecting specific metal bonding to nucleic acid bases: the tripodal nitrilotriacetato (nta) ligand-system. Crystal structures of [(nta)(adeninium)(aqua)nickel(II)] hydrate, [(nta)(diaqua)nickel(II)]·(cytosinium) hydrate, and [(nta)(diaqua)nickel(II)]·(cytosinium)·(cytosine) hydrate

Treatment of Ni(OAc) 2 and nitrilotriacetic acid (H 3nta) with nucleobases, adenine, 9-ethylguanine, cytosine, or uracil, provides a complex, [Ni(nta)(adeninium)(H 2O)] 2·5H 2O ( 1), and two salts, [Ni(nta)(H 2O) 2]·(cytosinium)·2H 2O ( 2) and [Ni(nta)(H 2O) 2]·(cytosinium)·(cytosine)·2H 2O ( 3), crystal structures of which were determined by X-ray diffraction, but no adduct for 9-ethylguanine and uracil. In 1, the adeninium moiety binds to the octahedral Ni 2+ atom, which is capped with a tripodal nta ligand to form the [Ni(nta)(H 2O)] − fragment, at the axial position through the N(7) atom with the formation of an interligand hydrogen bond or hydrogen bonds between the amino substituent N(6) of the base and a carboxylato oxygen or carboxylato oxygens of nta. In 2, the cytosinium molecule does not bind directly to the Ni 2+ atom but attaches to the [Ni(nta)(H 2O) 2] − fragment through triple hydrogen bonds. Complex 3 includes neutral and cationic cytosine molecules, neither of which bind to the Ni 2+ atom and to the [Ni(nta)(H 2O) 2] − fragment either, and, instead, there forms a cytosinium–cytosine complementary base-pair through triple hydrogen bonds. The observed base-specific binding property of the nta-capped octahedral Ni 2+ species, that is, adenine≫9-ethylguanine, cytosine, and uracil, is discussed in terms of interligand interactions.

Does the Hydrated Cytosine Molecule Retain the Canonical Structure? A DFT Study

The molecular geometry of complex of cytosine with 14 water molecules was calculated within the density functional theory using the B3LYP functional. The standard 6-31G(d) basis set has been employed. It was found that the interaction with water molecules forming a locked chain around cytosine results in a significant change of its gas-phase geometry. The structure of the hydrated nucleobase cannot be described by canonical chemical formula, and it is best approximated as a superposition of the oxoamino and zwitterionic hydroxoimino resonance structures. The unique features of the interaction of water with cytosine are also revealed: the formation of three hydrogen bonds with the participation of the oxygen atom of the carbonyl group and the presence of weak CH···O hydrogen bonds between the water molecules and the hydrophobic part of cytosine.

New supramolecular complexes of manganese(II) and cobalt(II) with nucleic bases. Crystal structures of [M(H2O)6(1-Mecyt)6][ClO4]2·H2O, [Co(1-Mecyt)4][ClO4]2 and [M(H2O)4(cyt)2][ClO4]2·2cyt·2H2O [M = CoII or MnII; cyt = cytosine; 1-Mecyt = 1-methylcytosine

The reactivity of cytosine [cyt] and 1-methylcytosine [1-Mecyt] towards transition metal ions Mn2+ and Co2+ has been tested through the analysis of their complexes. Two new compounds have been obtained from 1-Mecyt in aqueous medium, [M(H2O)6(1-Mecyt)6][ClO4]2·H2O [M = MnII1 or CoII2], and consist of hexaaqua ions linked to six 1-Mecyt molecules in such a way as to constitute a supramolecular cationic entity. Crystallization water molecules join the supramolecular assemblies by means of hydrogen bonds. Perchlorate anions, which are held in the crystal by electrostatic interactions with the cationic assemblies, insure the electroneutrality of the compounds. Compound 2 (pale pink crystals), when not filtered, over time disappears and gives rise to dark pink crystals of formula [Co(1-Mecyt)4][ClO4]23. Compound 3 contains four 1-Mecyt molecules directly linked through N(3) atoms to Co2+ ions in a tetrahedral arrangement. No water molecule is present. The [Co(1-Mecyt)4]2+ cationic units are joined together through hydrogen bonds and form a chain. Perchlorate anions hold these cationic chains together by means of electrostatic forces. The reaction of cyt with Mn2+ and Co2+ ions leads to compounds of formulae [M(H2O)4(cyt)2][ClO4]2·2cyt·2H2O [M = Mn2+4 or Co2+5] in which base pairs are formed between the two unco-ordinated cytosine molecules and those co-ordinated to the metal ion through the O(2) atom. Each metal ion is six-co-ordinated, being linked also to four water molecules. Perchlorate anions and crystallization water molecules interact with the base pairs and the metal ion through hydrogen bonds to form five-membered rings. The cobalt(II) compound constitutes the first example of cytosine–cobalt(II) co-ordination via O(2).

Implementation of Quantum Logic Gates by Nuclear Magnetic Resonance Spectroscopy

Using nuclear magnetic resonance techniques with a solution of cytosine molecules, we show an implementation of certain quantum logic gates (including NOT gate, square-root of NOT gate and controlled-NOT gate), which have central importance in quantum computing. In addition, experimental results show that nuclear magnetic resonance spectroscopy can efficiently measure the result of quantum computing without attendant wave-function collapse.

A theoretical investigation of tautomeric equilibria and proton transfer in isolated and monohydrated cytosine and isocytosine molecules

The results of an ab initio post Hartree–Fock (HF) comparable study of the relative stabilities and mechanisms of intramolecular proton transfer in isolated and monohydrated cytosine and isocytosine molecules are reported. The geometries of local minima and transition states were optimized without symmetry restrictions by the gradient procedure at the HF and MP2 levels of theory and were verified by energy second derivative calculations. The standard 6-31G(d) basis set was used. The single point calculations have been performed at the MP4(SDQ)/6-31G(d,p)//MP2/6-31G(d) and MP2/6-311++G(d,p)//MP2/6-31G(d) approximations. The post HF ab initio theory predicts different distributions of the tautomers for cytosine and isocytosine both in the gas phase and in polar media (Onsager's self-consistent reaction field model). The interactions with one water molecule change the order of relative stability of cytosine and isocytosine tautomers to those corresponding to the experimentally measured relative stabilities in polar solutions. Ab initio calculations predict the heights of the proton transfer barriers for monohydrated nucleic bases to be approximately three times lower compared with non-water-assisted processes.

Effects of Ionizing Radiation on Crystalline Cytosine Monohydrate

Possible radical reaction products observed when subjecting monohydrate crystals of the DNA base cytosine to ionizing radiation are characterized and analyzed by means of density functional theory. Comparison is made with data from a recently published detailed ESR and ENDOR study by Sagstuen et al. (Sagstuen, E.; Hole, E. O.; Nelson, W. H.; Close, D. M. J. Phys. Chem. 1992, 96, 8269), as well as earlier studies on methylcytosine and cytidine monophosphates. For cytosine monohydrate it is found, when comparing computed and measured radical hyperfine coupling constants, that products other than those initially assumed are possibly being formed. Instead of the original model that irradiation leads to the net reaction of dehydrogenation at the N1 position of one cytosine molecule and hydrogenation at the N3 position of a second cytosine, we present an alternative mechanism where water is involved in the process. This alternative mechanism leads to the formation of N3 hydrogenation and C5 hydroxylation net products, as the main reactions. Not only do the hyperfine couplings provide a better match for the latter but they are also energetically favored over the first mechanism.