Theoretical study of N<Subscript>4</Subscript>X (X = O,S, Se) systems

A series of N₄X (X = O, S, Se) compounds have been examined with ab initio and density functional theory (DFT) methods. To our knowledge, these compounds, except for the C_2v ring and the C_3v towerlike isomers of N₄O, are first reported here. The ring structures are the most energetically favored for N₄X (X = O and S) systems. For N₄Se, the cagelike structure is the most energetically favored. Several decomposition and isomerization pathways for the N₄X species have been investigated. The dissociation of C_2v ring N₄O and N₄S structures via ring breaking and the barrier height are only 1.1 and −0.2 kcal mol⁻¹ at the CCSD(T)/6-311+G*//MP2/6-311+G* level of theory. The dissociation of the cagelike N₄X species is at a cost of 12.1–16.2 kcal mol⁻¹. As for the towerlike and triangle bipyramidal isomers, their decomposition or isomerization barrier heights are all lower than 10.0 kcal mol⁻¹. Although the C_S cagelike N₄S isomer has a moderate isomerization barrier (18.3–29.1 kcal mol⁻¹), the low dissociation barrier (−1.0 kcal mol⁻¹) indicates that it will disappear when going to the higher CCSD(T) level. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

CRYSTAL STRUCTURE OF 1,3,5-TRIMETHYL-N4-HYDROXYCYTOSINE,AND ITS RELEVANCE TO THE MECHANISM OF HYDROXYLAMINE MUTAGENESIS

Abstract

1,3,5-Trimethyl-N⁴-hydroxycytosine, an analogue of the promutagenic N⁴-hydroxycytosine and 5-methyl-N⁴-hydroxycytosine nucleosides, crystallizes in the monoclinic space group P 2₁/n with cell dimensions at ?147°C: a = 7.1481(7), b = 9.2565(5), c = 13.3086(12) Å, β = 97.90(2)°, V = 872.24(13) ų, ρ_c = 1.426 Mg m^?3, Z = 4, F(000) = 401.39, μ = 0.91 mm^?1, λ(Cu) = 1.54056 Å, 20(max) = 139.3°. The crystal structure has been solved by X-ray difraction and refined to R = 3.7 % for 1457 reflections. Notwithstandin the steric hindrance imposed by methyl groups at both N(3) and C(5), the exocyclic N⁴-OH group is located essentially in the plane of the ring, giving rise to an “overcrowded” molecule, like that of 1,5,N⁴,N⁴-tetramethylcytosine. The conformational parameters have also been compared with those of a number of related and previously reported N(1)-substituted cytosines. In the present compound the N⁴-OH rotamer is in the anti conformation relative to the ring N(3), hence similar to that of one of the rotamers in N(1)-substituted N⁴-hydroxycytosine, which permits normal Watson-Crick base pairing of the latter, relevant to the mechanism of hydroxylamine mutagenesis.     

μ-1,2,4,5-Tetrazine-N:N-bis(pentaammineruthenium) tetracation: Synthesis and X-ray structure

The 2:1 reaction of [Ru(H₂O)₂(NH₃)₅]²⁺ with 1,2,4,5-tetrazine (tz) gives rise to the formation of the dinuclear complex ion [{Ru(NH₃)₅}₂(μ-tz-N¹:N⁴)]⁴⁺. Its tetraphenylborate and hexafluoro-phosphate salts have been fully characterized; the X-ray structure of the former has also been determined.     

Antifungal and antitumor activity of heterocyclic thiosemicarbazones and their metal complexes: current status

More than 75 substituted thiosemicarbazones and a number of metal complexes of each have been assayed for their antifungal activity. Their activity is significantly affected by the substituted groups attached at both¹ N and⁴ N of the thiosemicarbazone moiety. Greatest activity occurs for 2-substituted pyridine thiosemicarbazones with differences observed for 2-formylpyridine, 2-acetylpyridine and 2-benzoylpyridine derivatives and their metal complexes. Further, there are activity differences for⁴ N-alkyl-,⁴ N-aryl-,⁴ N-dialkyl- and 3-azacyclothiosemicarbazones and their metal complexes as well as changes in the substituent size among each of these subgroups. Cu(II) complexes are often more active than the uncomplexed thiosemicarbazones, with the latter showing similar activity to Ni(II) complexes in many instances. The reduction potential of the thiosemicarbazone ligand in a Cu(II) complex, the strength of the ligand field and various spectral properties can be correlated to the inhibitory activity.     

Synthesis and characterization of gallium complexes bearing N-arylmethylenethiobenzahydrazone ligands; crystal structure of diethyl[N-(4-N,N-dimethylamino)benzylidene thiobenzahydrazonato]gallium

Five diethylgallium complexes of type Et₂GaL [(L = N-(4-methoxy) benzylidenethiobenzahydrazonato (1), N-(3,4-dimethoxy)benzylidenethio benzahydrazonato (2), N-(4-N,N-dimethylamino)benzylidenethiobenza hydrazonato (3), N-(2-naphthyl)methylenethiobenzahydrazonato (4), N-(9-anthryl)methylenethiobenzahydrazonato (5)] have been synthesized by the reaction of triethylgallium with appropriate N-arylmethylene thiobenzahydrazones. The compounds obtained have been characterized by elemental analysis, ¹H NMR, IR and mass spectroscopies, respectively. The solid structure of 3 has been determined by X-ray single crystal analysis, in which Ga atom is four coordinate. The photoluminescent property of complex 1 was studied. The maximum emission wavelength is 475 nm upon radiation by UV light.     

Preparation of S-(N6,N6-dimethyladenosyl)-L-methionine

4′,5′-Unsaturated nucleosides are obtained by the action of 1,5-diazabicyclo-[5.4.0]undec-5-ene on N¹- and N³-(methyl 2,3,4-tri-O-acetyl-β-d-glucopyranosyluronate)-5-fluorouracil. The ²H₁ conformation of N¹- and N³-(methyl 4-deoxy-α-l-threo-hex-4-enopyranosyluronate)-5-fluorouracil has been established by ¹H-n.m.r. and c.d. methods. Interaction of the heterocyclic base and the double bond of the sugar moiety is demonstrated.     

Nickel(II) complexes of terdentate or symmetrical tetradentate Schiff bases: Evidence of the influence of the counter anions in the hydrolysis of the imine bond in Schiff base complexes

Two sets of ligands, set-1 and set-2, have been prepared by mixing 1,3-diaminopentane and carbonyl compounds (2-acetylpyridine or pyridine-2-carboxaldehyde) in 1:1 and 1:2 ratios, respectively, and employed for the synthesis of complexes with Ni(II) perchlorate, Ni(II) thiocyanate and Ni(II) chloride. Ni(II) perchlorate yields the complexes having general formula [NiL₂](ClO₄)₂(L = L¹ [N³-(1-pyridin-2-yl-ethylidene)-pentane-1,3-diamine] for complex 1 or L²[N³-pyridin-2-ylmethylene-pentane-1,3-diamine] for complex 2) in which the Schiff bases are monocondensed terdentate, whereas Ni(II) thiocyanate results in the formation of tetradentate Schiff base complexes, [NiL(SCN)₂] (L = L³[N,N′-bis-(1-pyridin-2-yl-ethylidine)-pentane-1,3-diamine] for complex 3 or L⁴ [N,N′-bis(pyridin-2-ylmethyline)-pentane-1,3-diamine] for complex 4) irrespective of the sets of ligands used. Complexes 5 {[NiL³(N₃)₂]} and 6 {[NiL⁴(N₃)₂]} are prepared by adding sodium azide to the methanol solution of complexes 1 and 2. Addition of Ni(II) chloride to the set-1 or set-2 ligands produces [Ni(pn)₂]Cl₂, 7, as the major product, where pn = 1,3-diaminopentane. Formation of the complexes has been explained by the activation of the imine bond by the counter anion and thereby favouring the hydrolysis of the Schiff base. All the complexes have been characterized by elemental analyses and spectral data. Single crystal X-ray diffraction studies confirm the structures of three representative members, 1, 4 and 7; all of them have distorted octahedral geometry around Ni(II). The bis-complex of terdentate ligands, 1, is the mer isomer, and complexes 4 and 7 possess trans geometry.     

Syntheses and antitumor activities of N′1,N′3-dialkyl-N′1,N′3-di-(alkylcarbonothioyl) malonohydrazide: The discovery of elesclomol

A series of N′¹,N′³-dialkyl-N′¹,N′³-di(alkylcarbonothioyl) malonohydrazides have been designed and synthesized as anticancer agents by targeting oxidative stress and Hsp70 induction. Structure–activity relationship (SAR) studies lead to the discovery of STA-4783 (elesclomol), a novel small molecule that has been evaluated in a number of clinical trials as an anticancer agent in combination with Taxol.     

Facile synthesis of carbon-11-labeled sEH/PDE4 dual inhibitors as new potential PET agents for imaging of sEH/PDE4 enzymes in neuroinflammation

To develop PET tracers for imaging of neuroinflammation, new carbon-11-labeled sEH/PDE4 dual inhibitors have been synthesized. The reference standard N-(4-methoxy-2-(trifluoromethyl)benzyl)benzamide (1) and its corresponding desmethylated precursor N-(4-hydroxy-2-(trifluoromethyl)benzyl)benzamide (2) were synthesized from (4-methoxy-2-(trifluoromethyl)phenyl)methanamine and benzoic acid in one and two steps with 84% and 49% overall chemical yield, respectively. The standard N-(4-methoxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide (MPPA, 4) and its precursor N-(4-hydroxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide (5) were synthesized from methyl 4-piperidinecarboxylate, propionyl chloride and (4-methoxy-2-(trifluoromethyl)phenyl)methanamine in two and three steps with 62% and 34% overall chemical yield, respectively. The target tracers N-(4-[¹¹C]methoxy-2-(trifluoromethyl)benzyl)benzamide ([¹¹C]1) and N-(4-[¹¹C]methoxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide ([¹¹C]MPPA, [¹¹C]4) were prepared from their corresponding precursors 2 and 5 with [¹¹C]CH₃OTf through O-[¹¹C]methylation and isolated by HPLC combined with SPE in 25–35% radiochemical yield, based on [¹¹C]CO₂ and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (A_M) at EOB was 370–740 GBq/μmol with a total synthesis time of 35–40-minutes from EOB.     

Fates of N′-Methylnicotinamide and Nicotinamide N-Oxide in Mice

This experiment was performed to investigate the possibility that N′ -methylnicotinamide (N′-methyl-3-pyridinecarboxamide) and nicotinamide N-oxide have niacin activity or not in animals. When 20 mg N′-methylnicotinamide per mouse was administered, urinary excretion of nicotinamide, N¹-methylnicotinamide (MNA), N¹-methyl-2-pyridone-5-carboxamide (2-Py), and N¹-methyl-4-pyridone-3-carboxamide (4-Py) increased 24-, 3-, 3-, and 3-fold, respectively, compared with the control values. The increased ratios of MNA, 2-Py, and 4-Py were almost the same as those when 20 mg nicotinamide was administered. Therefore, the relative activity of N′-methylnicotinamide to nicotinamide as niacin was considered to be about 1. When 20 mg nicotinamide N-oxide per mouse was administered, urinary excretion of nicotinamide, MNA, 2-Py, and 4-Py increased 6.4-, 1.8-, 1.6-, and 1.7-fold, respectively, compared with the control values. The increased ratios of MNA, 2-Py, and 4-Py were about 1/2 of those when 20 mg nicotinamide was administered, so the relative activity of nicotinamide N-oxide to nicotinamide as niacin is considered to be about 1/2. In conclusion, it was found the possibility that the reactions N′-methylnicotinamide → nicotinamide and nicotinamide N-oxide → nicotinamide occur, at least in mice, and that therefore N′-methylnicotinamide and nicotinamide N-oxide have niacin activity.     

Synthesis,Molecular Conformation and Activity Against Herpes Simplex Virus of (E)-5-(2-Bromovinyl)-2′-Deoxycytidine Analogs

Analogs of (E)-5-(2-bromovinyl)-2 ′-deoxycytidine (BrVdCyd) (1) by substitution at N⁴ were synthesized to impart resistance against deamination. The anti-HSV-1 activity and solution conformation of these analogs were determined. N⁴-Acetyl-BrVdCyd (2) was a potent inhibitor of HSV-1 replication whereas N⁴-propanoyl-BrVdCyd (3) had good activity and N⁴-Butanoyl-BrVdCyd (4) had only low activity against HSV-1 replication. N⁴-Methyl-BrVdCyd (5) was devoid of activity against HSV-1.     

Copper(II) complexes of new pentadentate bis(benzimidazolyl)-dithioether ligands: synthesis, structure, spectra and redox properties

Copper(II) complexes of a series of linear pentadentate ligands containing two benzimidazoles, two thioether sulfurs and a amine nitrogen, viz. N,N^′-bis{4^′-(2″-benzimidazolyl)(methyl)-3^′-thiabutyl}amine(L¹), N,N^′-bis{4^′-(2″-benzimidazolyl)(methyl)-3^′-thiabutyl}N-methylamine (L²), 2,6-bis{4^′-(2″-benzimidazolyl)(methyl)-3^′-thiabutyl}pyridine(L³), N,N^′-bis{4^′-(2″-benzimidazolyl)-2^′-thiabutyl}amine (L⁴), N,N^′-bis{4^′-(2″-benzimidazolyl)-2^′-thiabutyl}N-methylamine (L⁵) and 2,6-bis{4^′-(2″-benzimidazolyl)-2^′-thiabutyl}-3pyridine (L⁶) have been isolated and characterized by electronic absorption and EPR spectroscopy and cyclic and differential pulse voltammetry. Of these complexes, [Cu(L¹)](BF₄)₂ (1) and [Cu(L²)](BF₄)₂ (4) have been structurally characterized by X-ray crystallography. The coordination geometries around copper(II) in 1 and 4 are described as trigonal bipyramidal distorted square based pyramidal geometry (TBDSBP). The distorted CuN₃S basal plane in them is comprised of amine nitrogen, one thioether sulphur and two benzimidazole nitrogens and the other thioether sulfur is axially coordinated. The ligand field spectra of all the complexes are consistent with a mostly square-based geometry in solution. The EPR spectra of complexes [Cu(L¹)](BF₄)₂ (1), [Cu(L¹)](NO₃)₂ (2), [Cu(L²)](BF₄)₂ (4) and [Cu(L³)](ClO₄)₂ (6) are consistent with two species indicating the dissociation/disproportionation of the complex species in solution. All the complexes exhibit an intense CT band in the range 305-395 nm and show a quasireversible to irreversible Cu^II/Cu^I redox process with relatively positive E_1/2 values, which are consistent with the presence of two-coordinated thioether groups. The addition of N-methylimidazole (mim) replaces the coordinated thioether ligands in solution, as revealed from the negative shift (222-403 mV) in the Cu^II/Cu^I redox potential. The present study reveals that the effect of incorporating an amine nitrogen donor into CuN₂S₂ complexes is to generate an axial copper(II)-thioether coordination and also to enforce lesser trigonality on the copper(II) coordination geometry.     

Synthesis, characterization and X-ray crystal structure of [Re(L4)(CO)3]Br · 2CH3OH (L4 = N,N-bis[(2-diphenylphosphino)ethyl]methoxyethylamine): A model compound for novel cationic Tc(I)-tricarbonyl radiotracers useful for heart imaging

This report describes synthesis and evaluation of cationic complexes, [^99mTc(CO)₃(L)]⁺ (L = N-methoxyethyl-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (L1), N-[(15-crown-5)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (L2) and N-[(18-crown-6)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (L3)) as potential radiotracers for heart imaging. Preliminary results from biodistribution studies in female adult BALB-c mice indicated that the cationic ^99mTc(I)-tricarbonyl complex, [^99mTc(CO)₃(L2)]⁺, has a significant localization in the heart at 60 min post-injection. To understand the coordination chemistry of these bisphosphine ligands with the ^99mTc(I)-tricarbonyl core, we prepared [Re(CO)₃(L4)]Br (L4: N,N-bis[(2-diphenylphosphino)ethyl]methoxyethylamine) as a model compound. [Re(CO)₃(L4)]Br has been characterized by elemental analysis, IR, ESI-MS, NMR (¹H, ¹³C, ¹H-¹H COSY, and ¹H-¹³C HMQC) methods, and X-ray crystallography. In solid state, [Re(CO)₃(L4)]⁺ has a distorted octahedron coordination geometry with PNP occupying one facial plane. The chelator backbone adopts a “chair” conformation with phosphine-P atoms at equatorial positions and the amine-N at the apical site. In solution, [Re(CO)₃(L4)]⁺ is able to maintain its cationic nature with no dissociation of carbonyl ligands or any of the three PNP donors.     

Synthesis and crystal structure of a copper(II) complex of deprotonated N,N′-bis(2-pyridinecarboxamide)-2,2′-biphenyl: Comparative redox study of CuN4 pyridine amide complexes

A new distorted square planar (two CuN₂ planes making an angle of ∼43°) copper(II) complex [Cu(L⁴)] · 0.5EtOH · 0.5MeOH (1) of a deprotonated tetradentate pyridine amide ligand [H₂L⁴ = N,N′-bis(2-pyridinecarboxamide)-2,2′-biphenyl] has been synthesized and structurally characterized. Absorption and EPR spectroscopic properties have also been studied. The E_1/2 values (Cu^II/Cu^I redox process) of the title complex along with a selected group of structurally characterized CuN₄ pyridine amide complexes with systematically varied structural, electronic/steric, and chelate-ring size effects, imposed by the coordinating ligands, have been determined and the observed trend has been rationalized.     

Effect of Adding Methionine and Threonine to a Protein-free Diet on the Metabolism of Nicotinamide

We have been attempting to confirm the hypothesis that the excretion ratio of nicotinamide metabolites, [N¹-methyl-2-pyridone-5-carboxamide (2-Py) + N¹-methyl-4-pyridone-3-carboxamide (4-Py)]/N¹-methylnicotinamide (MNA), reflects the adequacy of amino acid nutrition, but not of niacin nutrition. It is known that methionine and threonine supplementation to a protein-free diet reduced body weight loss. In this paper, we investigated whether rats fed with a protein free-diet supplemented with methionine and threonine would result in this excretion ratio being increased or not. The body weight loss was markedly reduced by the supplementation with both amino acids, as has been reported, and under the conditions, the excretion ratio significantly increased. The activity of 4-Py-forming MNA oxidase, which controls the change in excretion ratio, also increased significantly. From the present results and our previous results, it was proved that the excretion ratio of nicotinamide metabolites, (2-Py +4-Py)/MNA, reflects the adequacy of amino acid nutrition, but not of niacin nutrition.     

An Assessment of Electronic Properties of Pyrimidine and Purine Nucleosides by 15N-NMR Spectroscopy

Abstract

An ¹⁵N-NMR study at natural abundance of 0⁴/N³-substituted pyrimidine and C⁶-substituted purine ribonucleosides has shown that the exact location of the protecting group (substituent) on either 0⁴ or N³ in pyrimidines has a strong influence on the electronic properties of the resultant pyrimidine system, mainly because of the change of state of hybridization of the N³-nitrogen. The basicity of N³ in some C⁴-substituted pyrimidines has been studied by following the ¹⁵N chemical shifts of protonated species in the presence of CF₃COOH both in DMSO and in CH₂Cl₂ solution. A comparison of the basic character of N³ in C⁴-substituted pyrimidine and of N¹ in C⁶-substituted purine nucleosides has shown that the magnitude of the ¹⁵N shift of N³ (or N¹) upon protonation is governed mainly by the electronic properties of the heteroatom linked to C⁴ (or C⁶). It also clearly emerged in this study that there is very litle difference in basicities of N³ of pyrimidine and N¹ of purine nucleosides despite the presence of the fused imidazole moiety in the latter.     

Synthesis and biological evaluation of bis-N2,N2′-(4-hydroxycoumarin-3-yl)ethylidene]-2,3-dihydroxysuccinodihydrazides

A series of N²,N²′-bis[4-hydroxycoumarin-3-yl)ethylidene]-2,3-dihydroxysuccino-hydrazides, containing 4-hydroxycoumarin, hydrazine and tartaric acid moieties, have been prepared and examined for possible biological activity. Several of these compounds exhibit promising HIV-1 integrase inhibition (IC₅₀ = 3.5 μM), and anti-T. brucei (32% viability) and anti-mycobacterial (Visual MIC90 = 15.63 μM) activity.     

Synthesis of copper(II) complexes with 3,5-bis(4,6-dimethylpyrimidin-2-yl)-4H-1,2,4-triazol-4-amine (L). Molecular and crystal structures of L and [Cu2L2Cl4]·2MeCN

A series of copper(II) complexes, i.e. Cu₂LCl₄, CuLCl₂·H₂O and [Cu₂L₂Cl₄]·2MeCN (8), based on a new potentially polytopic ligand, 3,5-bis(4,6-dimethylpyrimidin-2-yl)-4H-1,2,4-triazol-4-amine (3b, L), have been synthesized. The crystal structures of L and [Cu₂L₂Cl₄]·2MeCN were studied by X-ray single crystal analysis. The dinuclear compound [Cu₂L₂Cl₄]·2MeCN represents the first example of structurally characterized metal complexes with 3,5-di(pyrimidin-2-yl)-4H-1,2,4-triazol-4-amines. Both copper atoms have distorted tetragonal-pyramidal 3N + 2Cl environment. Surprisingly, in contrast to the complexes based on 3,5-di(pyridin-2-yl)-4H-1,2,4-triazol-4-amine (pyridinyl analog of L), the compound [Cu₂L₂Cl₄]·2MeCN adopts a dinuclear trans-(N′,N¹,N²)₂ double bridging binding mode which is due to tridentate coordination of two L molecules linking two copper atoms through N¹,N²-triazole and N′-pyrimidine atoms. It seems to be reasonable that it is methyl groups in pyrimidinyl moiety that obstruct the expected dinuclear (N′,N¹,N²,N″)₂ double bridging coordination being one of the most common for 4-substituted 3,5-di(pyridin-2-yl)-4H-1,2,4-triazoles and 3,5-di(pyridin-2-yl)-1,2,4-triazolates. Due to π-π stacking interactions, molecules of Cu₂L₂Cl₄ in the structure of [Cu₂L₂Cl₄]·2MeCN form 1D chains.     

Functional model for intradiol-cleaving catechol 1,2-dioxygenase: Synthesis, structure, spectra, and catalytic activity of iron(III) complexes with substituted salicylaldimine ligands

A series of mononuclear iron(III) complexes with containing phenolate donor of substituted-salicylaldimine based ligands [Fe(L¹)(TCC)] · CH₃OH (1), [Fe(L²)(TCC)] · CH₃OH (2), [Fe(L³)(TCC)] (3), and [Fe(L⁴)(TCC)] (4) have been prepared and studied as functional models for catechol dioxygenases (H₂TCC = tetrachlorocatechol, or HL¹ = N′-(salicylaldimine)-N,N-diethyldiethylenetriamine, HL² = N′-(5-Br-salicylaldimine)-N,N-diethyldiethylenetriamine, HL³ = N′-(4,6-dimethoxy-salycyl-aldimine)-N,N-diethyl-diethylenetriamine, HL⁴ = N′-(4-methoxy-salicylaldimine)-N,N-diethyl-diethylenetriamine). They are structural models for inhibitors of enzyme-substrate adducts from the reactions of catechol 1,2-dioxygenases. Complexes 1-4 were characterized by spectroscopic methods and X-ray crystal structural analysis. The coordination sphere of Fe(III) atom of 1-4 is distorted octahedral with N₃O₃ donor set from the ligand and the substrate TCC occupying cis position, and Fe(III) is in high-spin (S = 5/2) electronic ground state. The in situ prepared iron(III) complexes without TCC, [Fe(L¹)Cl₂], [Fe(L²)Cl₂], [Fe(L³)Cl₂], and [Fe(L⁴)Cl₂] are reactive towards intradiol cleavage of the 3,5-di-tert-butylcatechol (H₂DBC) in the presence of O₂ or air. The reaction rate of catechol 1,2-dioxygenase depends on the redox potential and acidity of iron(III) ions in complexes as well as the substituent effect of the ligands. We have identified the reaction products and proposed the mechanism of the reactions of these iron(III) complexes with H₂DBC with O₂.     

N4-hydroxycytidine-a new mutagen of a base analogue type

N⁴-hydroxycytidine (N⁴-OHcyd)¹ is incorporated into nucleic acids of a cytidine-requiring strain of S.typhimurium 1045 and can act mutagenically. The reversion frequency of pyrG^? → pyrG⁺ is 10–20 fold higher than the spontaneous background. N⁴OHcyd-induced revertants show a strong inhibitory effect in the presence of N⁴OHcyd. The influence of N⁴OHcyd on cytidine metabolism is discussed.