DNA hydrolysis promoted by 1,7-dimethyl-1,4,7,10-tetraazacyclododecane

Several acyclic and macrocyclic polyamines were evaluated for their ability to cleave DNA. 1,7-Dimethyl-1,4,7,10-tetraazacyclododecane (DMC) could hydrolyze double-strand DNA at a concentration of 25microM. pH 7.2 was the optimal condition to cleave DNA in the presence of DMC. Supercoiled DNA hydrolytic cleavage by DMC was supported by the evidence from free radical quenching and T4 ligase ligation.     

HeLa cells apoptosis induced by 1,7-dimethyl-1,4,7,10-tetraazacyclododecane

Preliminary pharmacological tests showed that 1,7-dimethyl-1,4,7,10-tetraazacyclododecane (DMC) had antitumor activity against HeLa and A549 cell lines in vitro. The HeLa cells apoptosis induced by DMC was examined by flow cytometric meter, and further confirmed by observing the morphological changes and DNA fragmentation. No observation of A549 cells induced apoptosis was observed by DMC.     

Synthesis, characterization and coordination chemistry of dibenzofuran derivatives of 1,4,7,10-tetraazacyclododecane

A 1,4-disubstituted dibenzofuran derivative of 1,4,7,10-tetraazacyclododecane (cyclen), L1, has been prepared by the direct reaction of cyclen and chloroacetyldibenzofuran and the mono-substituted derivative, L2, by reaction of chloroacetyldibenzofuran and 1,4,7-tris(t-butoxycarbonyl)-1,4,7,10-tetraazacyclododecane followed by deprotection with trifluoroacetic acid. The ligands were characterized by ¹H and ¹³C NMR spectroscopy, IR spectroscopy and mass spectrometry. The reaction of the 1,4-disubstituted dibenzofuran cyclen, L1, with Cu(ClO₄)₂·6H₂O in methanol yielded crystals of [CuL1](ClO₄)₂·MeOH·1/2H₂O that were suitable for single crystal structural analysis. The X-ray structure confirmed that the 1,4-disubstituted dibenzofuran cyclen had been formed. The copper(II) coordination sphere in the complex cation, [CuL1]²⁺, is occupied by four nitrogen atoms from the macrocycle and an amide oxygen donor from one dibenzofuran pendant group. As is typical for copper(II)-cyclen complexes, the Cu(II) centre sits above the plane of the macrocycle nitrogen towards the oxygen donor, in this case by 0.5 Å. Fluorescence emission studies indicate that coordination of the macrocycle to either copper(II) or zinc(II) results in a decrease in emission with respect to the emission of the pure ligand.     

The Zn(2+) complex of 1,4,7,10-tetraazacyclododecane as an artificial nucleobase

{2-Deoxy-3-O-[2-cyanoethoxy(diisopropylamino)phosphino]-5-O-(4,4'-dimethoxytrityl)-α-D- erythro-pentofuranosyl}-N-{2-[4,7,10-tris(2,2,2-trifluoroacetyl)-1,4,7,10-tetraazacyclododecan-1- yl]ethyl}acetamide (1) was prepared and incorporated into a 2'-O-methyl oligoribonucleotide. The hybridization of this oligonucleotide with complementary 2'-O-methyl oligoribonucleotides incorporating one to five uracil bases opposite to the azacrown structure was studied in the absence and presence of Zn(2+). Introduction of Zn(2+) moderately stabilized the duplex with U-bulged targets.     

Synthesis and DNA-cleavage properties of metal complexes of 1,4,7,10-tetraazacyclododecane (cyclen) functionalized with a pendant benzocrown ether

The synthesis and DNA-cleavage properties of a series of novel mononuclear Zn(II), Cu(II), and Co(II) complexes 2 of a crown-ether-functionalized cyclen ligand is described. The Cu complex 2b displayed the highest catalytic activity towards pUC 19 DNA. The effects of reaction time, complex concentration, and pH were investigated, showing that 2b readily and efficiently converts supercoiled (type I ) plasmid DNA to nicked (type II) DNA under physiological conditions (37 degrees, pH 7.4).     

N,N-expeditious dialkylation of cyclen (1,4,7,10-tetraazacyclododecane). An astonishing reactivity of cyclen tricarbonyl molybdenum and chromium complexes

After reaction with alkyl iodides and subsequent oxidative removal of the M(CO)₃ triprotection, molybdenum and chromium fac-LM(CO)₃ complexes of cyclen (L) unexpectedly lead to N¹,N⁷-dialkylated cyclen derivatives.     

Monometallic complexes of 1,4,7,10-tetraazacyclododecane containing an imidazolium side: synthesis, characterization, and their interaction with plasmid DNA

The synthesis of macrocyclic polyamine monometallic complexes containing imidazolium salt groups was reported. Their interaction with pUC19 plasmid DNA was studied. The result showed that these complexes can catalyze the DNA cleavage with unprecedented reactivity under physiological conditions.     

The thulium complex of 1,4,7,10-tetrakis{[N-(1H-imidazol-2-yl)carbamoyl]methyl}-1,4,7,10-tetraazacyclododecane (dotami) as a ParaCEST contrast agent

1,4,7,10-Tetrakis{[N-(1H-imidazol-2-yl)carbamoyl]methyl}-1,4,7,10-tetraazacyclododecane (dotami), a tetra(1H-imidazol-2-yl) derivative of the well-studied octadentate 1,4,7,10-tetrakis[(carbamoyl)methyl]-1,4,7,10-tetraazacyclododecane (dotam) ligand, was synthesized by reaction of 1,4,7,10-tetraazacyclododecane with N-(1H-imidazol-2-yl)chloroacetamide in high yield. Its tricationic thulium complex was isolated as a water-soluble chloride salt. The detection of the mildly acidic amide and amine protons by direct proton NMR in aqueous solution was unsuccessful, but such exchangeable protons could be detected via their chemical exchange-dependent saturation transfer (CEST) effect. The observed CEST effect was distinctly different from that found for respective dotam complexes and is, therefore, ascribed to exchangeable protons associated with the imidazole substituent.     

Efficient cycloreversion of cis,syn-thymine photodimer by a Zn2+–1,4,7,10-tetraazacyclododecane complex bearing a lumiflavin and tryptophan by chemical reduction and photoreduction of a lumiflavin unit

DNA photolyases (EC 4.1.99.3) are enzymes that catalyze photoreversion of cis,syn-thymine photodimer (T[c,s]T), which is one of major photolesion products in DNA, by utilizing UV light. In this work, we have designed and synthesized Zn²⁺–1,4,7,10-tetraazacyclododecane complexes bearing a lumiflavin and l-tryptophan (ZnL³) or l-phenylalanine (ZnL⁴) as artificial DNA photolyases. We have found that (ZnL³)_red, whose flavin unit was reduced in situ by Na₂S₂O₄, accelerates the photoreversion of T[c,s]T utilizing near-UV light in aqueous solution at pH 7.6 and 11. Interestingly, more efficient photoreversion of T[c,s]T was achieved by UV irradiation of an oxidized form of ZnL³ [(ZnL³)_ox] in the presence of an excess amount of Et₃N at pH 11. UV–vis and fluorescence measurements and action spectra showed that an oxidized form of flavin of (ZnL³)_ox was photoreduced by Et₃N into its reduced form (ZnL³)_red, which promoted the photoreduction of T[c,s]T. Comparison of the photochemical properties of ZnL³ with those of ZnL⁴ suggested that a tryptophan unit in ZnL³ contributed to the stabilities of the flavin through intramolecular photoinduced electron transfer.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

The structure of the 11-coordinate barium complex of the pendant-donor macrocycle 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane: an analysis of the coordination numbers of barium(II) in its complexes

The crystal structure of [Ba(DOTAM)Cl]₂(ClO₄)₂ · 2.7H₂O, is reported, where DOTAM is 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane [triclinic, space group, , a=937.6(2), b=1050.4(2), c=1476.6(3) pm, α=110.41(2), β=97.48(2), γ=97.75(2)°, Z=2, R=0.0423]. The structure consists of a dimer held together by four oxygen atoms bridging between the two Ba atoms. Each Ba is 11-coordinate, coordinated to four nitrogens from the macrocyclic ring, and four oxygens from the four pendant amide groups of DOTAM. In addition, each Ba has a coordinated chloride ion, as well as two bridging amide oxygens from the other member of the dimer. An analysis of the coordination numbers (CN) of Ba(II) complexes is presented. It is found that the CN of Ba(II) complexes ranges from 3 to 12, and is most commonly 9 with unidentate ligands. Higher coordination numbers of 10 and above are promoted by either polydentate ligands of denticity greater than six, or the presence of several ligands such as nitrate or acetate that form four-membered chelate rings. Lower coordination numbers of seven and below are promoted by increasingly large substitutents attached directly to the donor atoms of the ligand.     

A new macrocyclic tetraamine, 2,4-dinitrophenylcyclen (= 1-(2,4-dinitrophenyl)-1,4,7,10-tetraazacyclododecane):synthesis, cation reporter properties, and recognition of 1-methylthymine by its zinc(II) complex

A new functional macrocyclic ligand, 2,4-dinitrophenylcyclen (= 1-(2,4-dinitrophenyl)-1,4,7,10-tetraazacyclododecane), has been synthesized and isolated as its trihydrochloric acid salt (L·3HCl). The protonation constants (log K_n) for three secondary nitrogens of L were determined by potentiometric pH titration to be 10.10, 7.33 and <2 with I = 0.10 (NaNO₃) at 25°C. The 2,4-dinitrophenylaniline chromophore was proven to be a good reporter signaling proton- and metal-binding events in the macrocyclic cavity. The UV absorption band (λ_max 370 nm, 8200) of the 2,4-dinitrophenylaniline moiety at pH ≥ 9 becomes quenched as pH is lowered (to pH 3.1, where the major species is L·2H⁺), due to the strong protonation effect extended to the aniline moiety within the macrocyclic cavity. This is in sharp contrast to the pH-independent UV absorption (λ_max 390 nm, 14 000) of a reference compound, N,N-diethyl-2,4-dinitroaniline. The UV absorption band of L is shifted to lower wavelengths with Zn²⁺ (λ_max 320 nm), Cd²⁺ (λ_max 316 nm) and Pb²⁺ (λ_max 317 nm), while it almost disappears with Cu²⁺ and Ni²⁺. The 1:1 Zn²⁺ and Cu²⁺ complexes with L were isolated and characterized. The Zn²⁺ complex recognizes 1-methylthymine anion (MT⁻) in aqueous solution at physiological pH to yield a stable ternary complex ZnL-MT⁻. The X-ray crystal structure of ZnL-MT⁻ showed that Zn²⁺ is four-coordinate with three secondary nitrogens of L and the deprotonated imide anion that is cofacial to the 2,4-dinitrophenyl ring.     

Methylcytosine-selective fluorescence quenching by osmium complexation

We report on the control of the emission from a fluorophore fixed on DNA using the methylcytosine-selective addition of an osmium-bipyridine complex. We have synthesized DNA modified by a microenvironment-sensitive fluorophore, 2-dimethylamino-6-acyl-naphthalene. The emission from the fluorophore tethered to a probe DNA was effectively quenched by a methylcytosine glycol-osmium-bipyridine triad, which was located in the immediate neighborhood of the fluorophore. The discrimination of the cytosine methylation status at a methylation hot spot in the p53 gene was also executed using a well-designed fluorescent DNA probe.     

Thermodynamics of gallium complexation by human lactoferrin

Equilibrium constants for the successive binding of 2 equiv of Ga3+ to human lactoferrin have been measured by difference ultraviolet spectroscopy in 0.1 M 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid containing 5 mM bicarbonate at pH 7.4 and 25 degrees C. Ethylenediamine-N,N'-diacetic acid was used as the competing chelating agent. Values of the effective binding constants for the stated experimental conditions are log K1 = 21.43 +/- 0.18 and log K2 = 20.57 +/- 0.16. Comparison of these results with literature values for the gallium-transferrin binding constants indicates that lactoferrin binds gallium more strongly by a factor of approximately 90. The ratios of successive binding constants for the two proteins are essentially identical. A linear free energy relationship (LFER) for the complexation of gallium(III) and iron(III) has been prepared and used to estimate an iron(III)-lactoferrin binding constant for pH 7.4. The LFER prediction is compared with thermodynamic data on iron binding at pH 6.4 and gallium binding at pH 7.4. The results indicate that the ratio of iron binding constants for lactoferrin and transferrin is likely in the range of 50-90.     

Thermodynamics of complexation of lanthanides by methoxybenzoates

The thermodynamic parameters of complexation of lanthanide cations by ortho-, meta- and para- methoxybenzoates have been measured using potentiometric and calorimetric techniques at 25 °C and an ionic strength of 0.10 M (NaClO₄). The values of logβ₁₀₁ correlate well with the ligand acid values of pK_a, reflecting the strongly ionic nature of the metal-ligand interaction. No evidence is found for extra charge polarization in these aromatic ligands due to the lanthanide complexation.     

Magnesium transport by mitochondria

The pathways for the uptake and extrusion of Mg²⁺ by mitochondria are not well defined. the present evidence suggests that uptake occurs by nonspecific diffusive pathways in response to elevated membrane potential. There is disagreement as to some of the properties of Mg²⁺ efflux from mitochondria, but the reaction resembles K⁺ efflux in many ways and may occur in exchange for H⁺. Matrix free magnesium ion concentration, [Mg²⁺], can be measured using fluorescent probes and is set very close to cytosol [Mg²⁺] by a balance between influx and efflux and by the availability of ligands, such as P_i. There are indications that matrix [Mg²⁺] may be under hormonal control and that it contributes to the regulation of mitochondrial metabolism and transport reactions.     

Magnesium uptake by soybeans

Magnesium contents of soybean (Glycine max) roots increase and the K and Ca contents decrease with increased MgCl₂ concentrations in ambient solutions. The Mg uptake is inhibited when both Ca and K are present in the solution, but not by K or Ca alone. Chloride uptake, which is very low from the MgCl₂ solution, is greatly enhanced by the presence of K. The selectivity against Mg imparted by K + Ca appears to be at an external barrier for cation uptake as shown by its dependence on the presence of Ca in the external solution. The Ca content of roots is influenced only slightly by changes in external Ca concentrations from 10⁻⁴ to 10⁻²m, but that of shoots is greatly enhanced as the Ca concentration is increased or the K concentration is decreased. These effects on Ca contents are explained as arising from transport to the shoot without involvement of vacuoles of root cells.     

The complexation of trivalent actinides by TMDTA

The stability constants in 0.10 M (NaCl) ionic strength solution for the formation of MTMDTA^?1 (M=Am, Cm, Bk and Cf; TMDTA = trimethylenedinitrilotetraacetate) were measured by solvent extraction. The values are 13.45 (Am), 13.79 (Cm), 14.36 (Bk) and 14.66 (Cf) and are much lower than expected from the σpK_a of the TMDTA acid. The data do not allow a definite interpretation of this decreased stability which may be due to a generalized weaker bonding or to failure to form the 6-membered

chelate ring.     

The evaluation of Cr-curcumin-DNA complexation by experimental and theoretical approaches

Chromium(III) chloride mediates DNA-DNA cross-linking. Some chromium complexes promote programmed cell death in specific ligand environment through binding to DNA. One strategy that can be supposed for reduction of Cr³⁺ binding affinity to DNA is using curcumin as a chelator. In the current study, the [Cr(Curcumin)(EtOH)₂](NO₃)₂ (CCC) was synthesized and characterized by UV/Vis, FT-IR, CHN and spectrophotometric titration techniques. The mole ratio plot revealed a 1:1 complex between Cr³⁺ and curcumin in solution. Binding interaction of this complex with calf thymus-DNA (CT-DNA) was investigated using UV/Vis, circular dichroism (CD), FT-IR and cyclic voltammetry. The intrinsic binding constants of CCC with DNA, measured by UV/Vis and cyclic voltammetry, were 1.60 × 10⁵ and 1.13 × 10⁵, respectively. The thermodynamic studies showed that the reaction is enthalpy and entropy favoured. CD analysis revealed that only Λ-CCC interacts with DNA and Δ-CCC form has no tendency towards DNA. Based on FT-IR studies, it was understood that CCC interacts with DNA via minor groove binding. The docking simulation was carried out for finding the binding mode of CCC to DNA, too. All of data demonstrated that the curcumin significantly reduced the affinity of Cr³⁺ to the DNA and the form of Δ-CCC has no interaction with DNA.     

Enantiomer separation by complexation SFC on immobilized Chirasil-nickel and Chirasil-zinc

The use of complexation SFC for enantiomer separation of Lewis base selectands on chiral nickel(II)- and zinc(II)-bis[(3-heptafluorobutanoyl)-10-methylene-(1R)-camphora te] chemically bonded to poly(dimethylsiloxane) (Chirasil-nickel and Chirasil-zinc) and employed as Lewis acid selectors is described. The method is especially suited for less volatile and configurationally labile racemates. The variation of the experimental parameters temperature T, pressure p and density rho of the mobile phase carbon dioxide on the retention factor k, relative retention r and chiral separation factor alpha is studied, providing insights into the mechanisms of chiral recognition under supercritical conditions. For mecoprop methyl ester (methyl 2-(4-chloro-2-methylphenoxy)propanoate) an unusual increase of alpha at increased temperature is observed on Chirasil-nickel. Supercritical carbon dioxide does not inadvertently affect the complexation equilibria between Lewis donor selectands and the Lewis acid metal selectors during complexation SFC.