GSTM1 and XRCC3 Polymorphisms:Effects on Levels of Aflatoxin B1-DNA Adducts

Objective： Aflatoxin B1 （AFB1）, which can cause the formation of AFB1-DNA adducts, is a known human carcinogen. AFB1-exposure individuals with inherited susceptible carcinogen-metabolizing or repairing genotypes may experience an increased risk of genotoxicity. This study was designed to investigate whether the polymorphisms of two genes, the metabolic gene Glutathione S-transferase M1 （GSTM1） and DNA repair gene x-ray repair cross-complementing group 3 （XRCC3）, can affect the levels of AFB1-DNA adducts in Guangxi Population （n= 966） from an AFB1-exposure area. Methods： AFB1-DNA adducts were measured by ELISA, and GSTM1 and XRCC3 codon 241 genotypes were identified by PCR-RFLP. Results： The GSTM1-null genotype [adjusted odds ratio （OR） = 2.09; 95% confidence interval （CI） = 1.61-2.71] and XRCC3 genotypes with 241 Met alleles [i.e., XRCC3-TM and -MM, adjusted ORs （95% CI） were 1.43 （1.08-1.89） and 2.42 （1.13-5.22）, respectively] were significantly associated with higher levels of AFB1-DNA adducts. Compared with those individuals who did not express any putative risk genotypes as reference （OR = 1）, individuals featuring all of the putative risk genotypes did experience a significantly higher DNA-adduct levels （adjusted ORs were 2.87 for GSTM1-null and XRCC3-TM; 5.83 for GSTM1-null and XRCC3-MM）. Additionally, there was a positive joint effect between XRCC3 genotypes and long-term AFB1 exposure in the formation of AFB1-DNA adducts. Conclusion： These results suggest that individuals with susceptible genotypes GSTM1-null, XRCC3-TM, or XRCC3-MM may experience an increased risk of DNA damage elicited by AFB1 exposure.

Active Oxygen Radical Scavenging Ability of Water-Soluble β-Alanine C_(60) Adducts

Water-soluble b-alanine C60 adducts were synthesized, and the scavenging ability to superoxygen anion radical O2- and hydroxyl radical.OH were studied by autoxidation of pyrogallol and chemiluminescence, respectively. It was found thatβ-alanine C60 adducts showed an excellent efficiency in eliminating superoxygen anion radical and hydroxyl radical. The 50% inhibition concentration (IC50) for superoxygen anion radical and hydroxyl radical were 0.15 mg/mL and 0.048 mg/mL, respectively. The difference should be mainly attributed to the different scavenging mechanisms.

Four New Phloroglucinol-Terpene Adducts from the Leaves of Myrciaria cauliflora

Myrcauones A-D(1-4),four new phloroglucinol-terpene adducts were isolated from the leaves of Myrciaria cauliflora.Their structures with absolute configurations were elucidated by combination of spectroscopic analysis,single crystal X-ray diffraction,and electronic circular dichroism(ECD)calculations.Compound 1 was a rearranged isobutylphloroglucinol-pinene adduct featuring an unusual 2,3,4,4a,10,11-hexahydro-1H-3,11a-methanodibenzo[b,f]oxepin backbone.Compound 4 showed moderate antibacterial activity against Gram-positive bacteria including multiresistant strains.

Non-covalent Bonded 3D Supramolecular Architectures Based on Acid-base Adducts

Two novel acid-base adducts,[H2L1^2＋]（Hpbda）2（1,L1 = 1,4-di（lH-imidazol-4-yl）benzene,H2pbda = 1,4-benzenedicarboxylic acid） and[H2L2^2＋]（NO3）2（2,L2 = l,4-di（l-carboxymethyl-imidazol-4-yl）benzene）,have been prepared and characterized by single-crystal X-ray diffraction,IR spectroscopy and elemental analysis.Compound 1 crystallizes in monoclinic,space group P21/n with a = 5.3525（11）,b = 9.1471（19）,c = 19.314（4） ？,β = 92.342（3）°,V= 944.8（3） A°3,Z = 2,C16H16N6O（10）,Mr = 452.35,Dc = 1.590 g/cm^3,μ = 0.135 mm^-1,S = 1.058,F（000） = 468,the final R = 0.0661 and wR = 0.1887 for 2298 observed reflections（I〉 2σ（I））.Compound 2 crystallizes in monoclinic,space group P21/c with a = 9.6923（10）,b = 17.2950（17）,c = 7.1880（7） ？,β =94.801（2）°,V= 1200.7（2）A°3,Z = 2,C（28）H（22）N4O8,Mr = 542.50,Dc = 1.501 g/cm^3,μ = 0.112 mm^-1,S= 1.060,F（000） = 564,the final R = 0.0394 and wR = 0.1017 for 2768 observed reflections（I 〉2σ（I））.In the title compounds,both of L1 and L2 ligands act as weak base to accept protons to exhibit diprotonated H2L1^2＋ and H2L2^2＋ form,which can effectively employ as hydrogen bonding donors to combine anion moieties to form binary adducts respectively.In the crystal packing diagram of two polymers,there exist extensive noncovalent interactions including charge-transfer interactions,C（N）-H…π and N-H…O,C-H…O,O-H…O hydrogen bonding interactions between co-crystal moieties which consolidate the structures of supramolecular polymers,thus generating three-dimensional（3D） frameworks.

Biological transformation,kinetics and dose-response assessments of bound musk ketone hemoglobin adducts in rainbow trout as biomarkers of environmental exposure

Low levels (ng/g) of musk ketone (MK),used as a fragrance additive in the formulation of personal care products,are frequently detected in the water and other environment.Thus,aquatic organisms can be continuously exposed to MK.In this study,kinetics and dose-response assessments of 2-amino-MK (AMK) metabolite,bound to cysteine-hemoglobin (Hb) in rainbow trout,formed by enzymatic nitro-reduction of MK have been demonstrated.Trout were exposed to a single exposure of 0.010,0.030,0.10,and 0.30 mg MK/g fish.Tw...

Improved preparation and identification of aristolochic acid-DNA adducts by solid-phase extraction with liquid chromatography-tandem mass spectrometry

Aristolochic acid （AA） is a known nephrotoxin and potential carcinogen, which can form covalent DNA adducts after metabolic activation in vivo and in vitro. A simple method for preparation and characterization of aristolochic acid-DNA adducts was developed. Four AA-adducts were synthesized by a direct reaction of AAI/AAII with 2′-deoxynucleosides. The reaction mixture was first cleaned-up and pre-concentrated using solid phase extraction （SPE）, and further purified by a reversed-phase high performance liquid chromatography （HPLC）. By the application of developed SPE procedure, matrices and byproducts in reaction mixture could be greatly reduced and adducts of high purity （more than 94% as indicated by HPLC） were obtained. The purified AA-DNA adducts were identified and characterized with liquid-electrospray ionization-quadrupole-time of flight-mass spectrometry （LC-ESI-Q-TOF-MS/MS） and LC-Diode array detector-fluorescence （LC-DAD-FL） analysis. This work provides a robust tool for possible large-scale preparation of AA-DNA adduct standards, which can promote the further studies on carcinogenic and mutagenic mechanism of aristolochic acids.

A convenient and stereoselective synthesis of (Z)-allyl selenides via Sm/TMSCl system-promoted coupling of Baylis-Hillman adducts with diselenides

A simple and convenient procedure for stercoselective synthesis of （Z）-allyl selenides has been developed by a one-pot reaction of diselenides with Baylis-Hillman adducts in the presence of samarium metal-trimethylsilyl chloride under mild conditions. Presumably, the diselenides are cleaved by Sm/TMSCI system to form selemde anions, which then undergo SN2＇ substitution of Baylis-Hillman adducts to produce the （Z）-allyl selenides.

STUDIES ON CYCLOPENT-2-ENONE: (Ⅲ) THE STUDY ON DECONJUGATION OF CYCLOPENT -2-ENONE ALDOL ADDUCTS

Deconjugation of cyclopent-2-enone aldols were attempted under various conditions, and the desired deconjugated product was achieved via dianion approach. Various results obtained in this study are explained by structure and transition state analysis.

Theoretical Study of Nonclassical Platinum Complexes Bonding to Purine Bases: How the Long-lived Monofunctional Adducts Can Be in Existence?

The B3LYP/6-31G^＊ level of theory was used for the optimization of nonclassical platinum drugs with planar aromatic heterocycle ligands in addition to their monoaqua species, diaqua species and monofunctional adducts. Single point calculations were performed on optimized geometries using the MP2/6-31G^＊＊ method, and the Lanl2dz pseudo potential for the Pt atom remained constant in all calculations. It can be easily seen that the trans effect can influence both geometrical structures and bond dissociating energies （BDEs）. On the basis of our calculation, we get that the long-lived monofunctional adducts with chloride ligand may be in existence, because they possessed higher stability energies, easily dissociated chloride compared with the monoaqua species dissociating chloride and that replacement of the first chloride by bases became exothermic in solution. Our calculated results also demonstrate that the strongest H-bonds appear in the complexes of q-wG and t-wG using different methods. In comparison with adenine complexes, the corresponding guanine complexes possess larger interaction energies as well as higher stability energies either corrected by basis set superposition error （bsse） of Boys-Bernardi counterpoise method or uncorrected both in gas phase and in solution with one exception that the stability energy of q-CIA complex in solution is larger than that of q,CIG complex. Finally, the nature of bond was analyzed in terms of partial charges distribution based on NBO population.

Chlorine-radical Induced Oxidation of Glyoxal and Glyoxal-S(IV) Adducts in the Aqueous Phase

A laser flash photolysis study of the reactivity of Cl˙with glyoxal, glyoxal mono- and dibisulfite adducts, 1-hydroxy-2, 2-diol-ethanesulfonate and 1, 2-dihydroxy-1, 2-ethanedi sulfonate in the aqueous phase was carried out. The obtained rate constants can be used for atmospheric modeling.

Mulberry Diels-Alder-type adducts:isolation,structure,bioactivity,and synthesis

Mulberry Diels-Alder-type adducts(MDAAs)are unique phenolic natural products biosynthetically derived from the intermolecular[4+2]-cycloaddition of dienophiles(mainly chalcones)and dehydroprenylphenol dienes,which are exclusively distributed in moraceous plants.A total of 166 MDAAs with diverse skeletons have been isolated and identified since 1980.Structurally,the classic MDAAs characterized by the chalcone-skeleton dienophiles can be divided into eight groups(Types A−H),while others with non-chalcone dienophiles or some variations of classic MDAAs are non-classic MDAAs(Type I).These compounds have attracted significant attention of natural products and synthetic chemists due to their complex architectures,remarkable biological activities,and synthetic challenges.The present review provides a comprehensive summary of the structural properties,bioactivities,and syntheses of MDAAs.Cited references were collected between 1980 and 2021 from the SciFinder,Web of Science,and China National Knowledge Internet(CNKI).

STUDY ON GMA-DNA ADDUCTS

Objective. DNA modification fixed as mutations in the cells may be an essential factor in the initiation step of chemical carcinogenesis. In order to explore the mechanism of gene mutation and cell transformation induced by glycidyl methacrylate (GMA), the current test studied the characteristics of GMA DNA adducts formation in vitro. Methods. In vitro test, dAMP, dCMP, dGMP, dTMP and calf thymus DNA were allowed to react with GMA (Glycidyl Methacrylate). After the reaction, the mixtures were detected by UV and subjected to reversed phase HPLC on ultrasphere ODS reversed phase column, the reaction products were eluted with a linear gradients of methanol (solvent A) and 10mmol/L ammonium formate, pH5 0 (solvent B). The synthesized adducts were then characterized by UV spectroscopy in acid (pH1 0), neutral (pH7 2), alkaline (pH11 0) and by mass spectroscopy. Results. The results showed that GMA could bind with dAMP, dCMP, dGMP and calf thymus DNA by covalent bond, and the binding sites were specific (N 6 of adenine, N 3 of cytosine). Meanwhile, a main GMA DNA adduct in the reaction of GMA with calf thymus DNA was confirmed as N 3 methacrylate 2 hydroxypropy1 dCMP. Conclusions. GMA can react with DNA and /or deoxynucleotide monophosphate and generate some adducts such as N 6 methacrylate 2 hydroxypropyl dAMP and N 3 methacrylate 2 hydroxypropyl dCMP, ets. Formation of GMA DNA adducts is an important molecular event in gene mutation and cell transformation induced by GMA.

Carcinogen-Macromolecular Adducts As Biomarkers in Human Cancer Risk Assessment

Substantial data have been generated during the past 5 years in both experimental systems and human populations which shed light on the potential role of carcinogen-macromolecular adducts in human cancer risk assessment. The use of DNA and protein adducts is based on the fundamental concept in chemical carcinogenesis that most genotoxins are metabolized to electrophilic 'ultimate' carcinogens that are capable of forming covalent adducts with cellular macromolecules. This report examines the relative usefulness and limitations of using DNA and protein adducts and related techniques for assessing human exposure to genotoxic carcinogens. Data discussed in this report clearly demonstrate that these biomarkers not only allow early detection of potential cancer hazard in humans, but they can also significantly increase the power of conventional cancer epidemiological studies in determining true causal relationships. In addition, such biomarkers can improve extrapolation of cancer risks from laboratory animals to humans or from one human population to another.

α-OXOKETENE CYCLIC DITHIOACETAL CHEMISTRY(XⅢ)-THE ETHERIFYING REACTION ON THE ADDUCTS OF ALIPHATIC α-OXO KETENE CYCLIC DITHIOACETALS WITH ALLYL MAGNESIUM BROMIDE

Aliphatic α-oxo ketene cyclic dithioacetals 1 were reacted with allyl magne- sium bromide to afford the 1,2-addition products 2.Catalyzed by boron trifluoride etherate,the adducts 2 were etherified by methanol to afford the corresponding methyl ethers 3.This process provides a new method for the protection of the acid sensitive hydroxyl group in 2 under mild condition.

Pre-Chelates, Post-Adducts and Implexes: A perspective proposal for the future of medicinal chemistry

The title of this little assay coins three new words: Pre-Chelates, Post-Adducts and Implexes. These, very daring new excursions into the scientific English language, come from the developments of Quelamycin and Sodium L-Thioproline, through our different group studies arriving to cancer reversal by a dual strategy. It is enough to read all our published materials, cites and related papers, dealing more or less with the chemistry and possible mechanism of action of these compounds, to gather somewhat what signified our monomeric-triferric-doxorubicine, as possibly one of the first Pre-Chelates and our Sodium L-Thioproline, probably as one of the first Post-Adducts. Both molecules come to the human patients with cancer blood from the exterior. After this indication, it will be proposed a seed concept of a new type of molecules, the “Implexes” in which the metals will be embraced instead of being linked.

Thermochemical Parameters of Tetramethylthiourea Adducts of Certain Metal(II) Bromides

Complexes of the general formula [MBr2(TMTU)n] (where M is Mn, Fe, Co, Ni, Cu, Zn or Cd;TMTU is Tetramethylthiourea;n is 0.75, 2 or 3) were obtained by the reaction of salts and ligand in solution. The bromides were selected among several other salts because they had thermochemical data in the literature. Properties as capillary melting points;C, H, N, Br and metal contents;TG/DTG and DSC curves;and IR and electronic spectra were determined. The values of several thermodynamic parameters for the complexes were found by solution calorimetry. From them, the standard enthalpies of the metal-sulphur coordinated bonds were calculated. The standard enthalpies of the formation of the gaseous phase adducts also were estimated.

Review: Adducts and Clusters in Chromatography, Mass Spectrometry and Nature

The word “clusters” in scientific terminology as aggregated molecules or atoms appeared in chemistry relatively recently. The terms clusters have been used intensively since the discovery of fullerenes. The term cluster is not a new one for other branches of science such as astrophysics-star cluster, globular cluster, galaxy cluster, in biology and medicine-cancer cluster, genetic cluster, or in computing-data cluster. Adducts in chemistry were known significantly earlier. Both clusters and adducts are assemblies of atoms or molecules that are held together by weak van der Waals or London dispersion forces. Clusters are homogeneous and usually consist of one sort of atom or molecule. Clusters can also be a host for other types of atoms or molecules. Adducts usually consist of two different types of molecules, one of which is the host molecule. Both clusters and adducts are well defined by IUPAC. The present short review describes some important phenomena of these intriguing associations, which have interest for chemical extraction, separation, analysis, and for nature in general.

Hemoglobin Adducts as Biomarkers of Exposure to and metabolic Activation of Carcinogenic Tobacco-Specific Nitrosamines

The carcinogenic tobacco-specific nitrosamines N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) form hemoglobin adducts in laboratory animals and humans. These adducts release 4-hydroxy-l-(3-pyridyl)-l-butanone (HPB) upon mild base hydrolysis. HPB released from human hemoglobin can be quantified by gas chromatography-mass spectrometry. It is the only available biochemical marker for determination of exposure to, and metabolic activation of, carcinogens present only in tobacco. Levels of HPB were highest in snuff-dippers, followed by smokers and nonsmokers. Large interindividual variations in adduct levels were observed. The relationship between HPB levels in globin and DNA of rats treated with NNK has been investigated in order to aid in interpretation of the data from humans. These studies have provided the initial database for understanding the metabolic activation of tobacco-specific nitrosamines in humans.

Spectral Differences of the Molecule-ion Adducts of β-Cyclodextrin and Lithium Carbonate

A small shielding effect on the hydrogen atoms of chiral carbons of β-cyclodextrin （β-CD） was detected by 1H nuclear magnetic resonance, but a large environmental change of the chiral carbon atoms at high concentration ratios of lithium carbonate （Li2CO3） to β-CD was observed by polarimetry in aqueous solution. These findings urged us to investigate whether different formation conditions of the molecule-ion system between Li2CO3 and β-CD in solid state were involved in different spectral performances. To answer the question, we prepared three adducts of Li2CO3 to β-CD, i.e., samples 1, 2, and 3, by magnetic stirring, solvothermal and grinding conditions, respectively. Powder X-ray diffraction and Fourier transformation infrared spectroscopy provided the information of formation of the three molecule-ion adducts. Besides, scanning electron microscope images provided different surface information of the three adducts. Further, significant spectral differences in thermal behavior of these adducts were found by thermogravimetry and derivative thermogravimetry.

Significant Positive Correlation of Plasma BPDE-Albumin Adducts to Urinary 1-Hydroxypyrene in Coke Oven Workers

Objective To investigate the application of BPDE-albumin adducts as monitoring biomarkers for coke oven workers exposed to polycyclic aromatic hydrocarbons （PAHs） and to explore possible relationship between BPDE-albumin adducts and urinary 1-hydroxypyrene （1-OHP） levels in them. Methods Thirty-seven coke oven workers from a coke plant and 47 controls without the occupational exposure to PAHs were recruited in this study. The levels of plasma BPDE-albumin adducts and urinary 1-OHP were analyzed using high performance liquid chromatography. Results The median levels of BPDE-albumin adducts （42.10 fmol/mg albumin） and urinary 1-OHP （5.46 μmol/mol creatinine） were significantly higher in coke oven workers than in controls （14.16 fmol/mg albumin, 2.96μmol/mol creatinine, respectively; P〈0.01）. Multiple logistic regression analysis showed that coke oven workers were at higher risk of having BPDE-albumin adduct levels above 25.30 μmol/mg albumin （OR=1.79, P〈0.01） and urinary 1-OHP levels above 4.13 μmol/mol creatinine （OR=2.45, P〈0.05）. There was a positive correlation between the levels of BPDE-albumin adducts and urinary 1-OHP in all subjects （rs=0.349, P〈0.01）. Conclusion BPDE-albumin adduct is a useful biomarker for monitoring long-term exposure to PAHs, and plasma BPDE-albumin adducts level is significantly correlated to urinary 1-OHP levels in coke oven workers.