Oxygen Atom from Carbonyl Group as an Important Binding Agent to the G-Quadruplex - Study Case of Flavonoids.

In the field of anticancer therapy study it is of great interest to find effective G-quadruplex ligands which may be of potential use in medical treatment or cancer prevention. Since among the compounds of natural origin, flavonoids have attracted notable attention because of their unique properties and promising therapeutic applications, an interesting question was to identify the flavonoid structural features that could provide effective binding properties toward G-quadruplex. By using electrospray ionization mass spectrometry, followed by the survival yield method, it has been shown that the flavonoid molecules which contain an available C4=O carbonyl group form more stable adducts with G-tetrads than the other ones. Molecular docking has shown that C4=O carbonyl group can be a source of hydrogen bonds and/or π-stacking interactions. Therefore, the flavonoid molecules which contain an available C4=O carbonyl group can be regarded as good binders of G-quadruplexes.

Comment on the "Does saponin in quinoa really embody the source of its bitterness?"

Saponins are considered the main source of the bitter taste of quinoa, however, it has not been confirmed by Song et al. (2024). These authors suggested that saponin extracts contribute to the umami taste, however, the stronger source of the bitter taste may be the flavonoids contained in the extracts. It is an interesting finding in view of the flavonoids role in the field of food sciences. The UPLC-MS results showed that besides saponins, also polyphenols were present in the analyzed samples. However, the presented results of UPLC-MS analysis should be substantially improved, mainly with respect to the reported accurate masses and retention times, as described in details in this comment.

Study of protonated dimers of cytosine, cytidine, and deoxycytidine using survival yield method and quantum mechanics calculations.

RATIONALE: Cytosine and its conjugates are prone to form protonated, triply-bonded dimers. Therefore, the nucleic-acid cytosine-rich sequence forms the four-stranded noncanonical secondary structure known as the intercalated motif (i-motif). This process has resulted in studies on cytosine protonated dimers. This communication focuses on the protonated dimers of cytosine and its nucleoside using the survival yield (SY) method and quantum mechanics calculations. METHODS: To obtain the precursor ion fragmentation curve, the plot of SY against Ecomδ , the product ion spectra of the protonated dimers were obtained using a Waters/Micromass Q-TOF Premier mass spectrometer. Quantum mechanics calculations were performed using GAUSSIAN 16, and full geometry optimizations and energy calculations were performed within the density functional theory framework at B3LYP/6-31G(d,p). RESULTS: The precursor ion fragmentation curve allowed the rating of the gas-phase stabilities of the analyzed protonated dimers. Substitution of sugar moiety at N1 cytosine atom decreased the gas-phase stabilities of the protonated dimers. The deoxycytidine dimer was found to be more stable than the cytidine dimer and cytidine-deoxycytidine dimer. Quantum chemical calculations indicated that cytosine aminohydroxy tautomer may be involved in the formation of protonated cytosine-cytosine nucleoside dimers but not in the formation of cytosine dimers. CONCLUSIONS: The results obtained for nucleoside dimers indicated that the SY method may reflect the i-motif stabilities observed under physiological conditions. Therefore, the analysis of other protonated dimers of variously substituted cytosine-cytosine nucleoside using the SY method may be important to study the effect of cytosine substitution on the i-motif stabilities. Cytosine tautomer containing C2-OH… N(2H)-C4 moiety may be involved in the formation of protonated cytosine-cytosine nucleoside dimers.

Binding of Quercetin Derivatives toward G-Tetrads as Studied by the Survival Yield Method.

Recently, much interest has been devoted to finding effective G-quadruplex ligands, both of synthetic or natural origins, which may be of potential use in the field of cancer therapy. Among compounds of natural origin, a common flavonol quercetin has attracted notable attention. Yet, only a modest number of papers have been concerned with a comparison of quercetin conjugates binding to G-quadruplexes. In this study, we applied the survival yield (SY) method in order to compare the stability of G-tetrad complexes with quercetin and its conjugates, namely, 3-O-glycosides and O-methylated conjugates. According to the determined values of Ecomδ50, flavonol glycosides bind most effectively with G-tetrads, whereas, among flavonols, 3-O-methylquercetin makes the most effective bonds. Because the aglycone structure is of crucial importance for biological processes, 3-O-methylquercetin seems to be a suitable candidate for anticancer therapeutics, and the extracts from the plants, which contain high amounts of 3-O-methylquercetin or its glycosides, should be considered as interesting materials for preparation of pharmaceuticals or dietary supplements.

Exploring Glycosylated Soy Isoflavones Affinities toward G-tetrads as Studied by Survival Yield Method.

Taking soy-based food supplements for menopausal symptoms by women may reduce the risk of cancer. Therefore, the interaction between nucleic acids (or their constituents) and ingredients of the supplements, e. g., isoflavone glucosides, on the molecular level, has been of interest with respect to cancer therapy. In this work, the interaction between isoflavone glucosides and G-tetrads, namely [4G+Na]+ ions (G stands for guanosine or deoxyguanosine), were analyzed by using electrospray ionization-collision induced dissociation-mass spectrometry (ESI-CID-MS) and survival yields method. The strength of isoflavone glucosides-[4G+Na]+ interaction in the gas phase was determined from Ecom50 - the energy required to fragment 50 % of selected precursor ions. Glycitin-[4G+Na]+ interaction was found to be the strongest, and the interaction between isoflavone glucosides and guanosine tetrad was established to be stronger than that between isoflavone glucosides and deoxyguanosine tetrad.

Gas-Phase Internal Ribose Residue Loss from Mg-ATP and Mg-ADP Complexes: Experimental and Theoretical Evidence for Phosphate-Mg-Adenine Interaction.

Gas-phase decompositions of magnesium complexes with adenosine-5'-triphosphate (ATP) and adenosine-5'-diphosphate (ADP) were studied by using electrospray ionization-collision-induced dissociation-tandem mass spectrometry, in the negative ion mode. The loss of internal ribose residue was observed and was found to occur directly from the [ADP-3H+Mg]- ion. The occurrence of this process indicates the presence of a strong phosphate-Mg-adenine interaction. The performed quantum mechanics calculations confirmed the occurrence of this interaction in the [ADP-3H+Mg]- ion, namely the presence of Mg-N7 bond and hydrogen bond between the phosphate oxygen atom and amino group. Although the finding concerns the gas phase, it indicates that phosphate-Mg-adenine interaction may be also of importance for biological processes. The loss of an internal ribose residue was also observed for calcium and zinc complexes with ATP/ADP as well as for magnesium complexes with guanosine-5'-triphosphate (GTP) or guanosine-5'-diphosphate (GDP). Therefore, it is reasonable to conclude that the presence of the phosphate-metal-nucleobase interaction is a feature of gas phase [NDP-3H+metal]- ion (NDP, nucleoside-5'-diphosphate) and may also be important for biological processes.

Ethoxylated Butoxyethanol-BADGE Adducts-New Potential Migrants from Epoxy Resin Can Coating Material.

The acetonitrile extracts of can-coating materials have been analyzed by using high-pressure liquid chromatography/electrospray ionization-mass spectrometry (HPLC/ESI-MS). On the basis of detected ions [M + H]+, [M + NH4]+, [M + Na]+ and product ions, the ethoxylated butoxyethanol-bisphenol A diglycidyl ether adducts were identified in two of the analyzed extracts. Although the oxyethylene unit-containing compounds are widely used for the production of different kinds of materials, the ethoxylated species have not been earlier detected in epoxy resin can-coatings.

2,2-Bis(4-Hydroxyphenyl)-1-Propanol-A Persistent Product of Bisphenol A Bio-Oxidation in Fortified Environmental Water, as Identified by HPLC/UV/ESI-MS.

Biodegradation of bisphenol A in the environmental waters (lake, river, and sea) has been studied on the base of fortification of the samples taken and the biodegradation products have been analyzed using HPLC/UV/ESI-MS. Analysis of the characteristic fragmentation patterns of [M-H]- ions permitted unambiguous identification of the biodegradation products as 2,2-bis(4-hydroxyphenyl)-1-propanol or as p-hydroxyacetophenone, depending on the type of surface water source. The formation of 2,2-bis(4-hydroxyphenyl)-1-propanol was much more common than that of p-hydroxyacetophenone. Moreover, 2,2-Bis(4-hydroxyphenyl)-1-propanol has not been further biodegraded, in contrast to the p-hydroxyacetophenone, which was further mineralized. It has been proved, for the first time, that 2,2-bis(4-hydroxyphenyl)-1-propanol can be regarded as persistent product of bisphenol A biodegradation in the fortified environmental waters.

HPLC/ESI-MS identification of diastereomers of Impurity E - Degradation products of cefaclor.

A seven years old sample of cefaclor stored in room conditions, as a solid, has been analyzed by using high performence liquid chromatography/electrospray ionization-mass spectrometry. As a result of the sample degradation process, two diastereomers of Impurity E have been found to have formed. It is reasonable to assume that the diastereomers are formed due to the isomerization of C6 carbon atom. They have almost identical fragmentation patterns in both positive and negative ion mode. On the other hand, the diastereomers have different efficiencies of formation of dimer ions, under ESI conditions, especially in negative ion mode.

Gas-phase hydration of Mg2+ complexes with deprotonated uracil, thymine, uridine, and thymidine.

The gas-phase hydration of Mg2+ complexes with deprotonated uracil (U), thymine (T), uridine (Ur , uracil riboside), and thymidine (Tdr , thymine deoxyriboside) was studied. The aim of the work was to analyze the hydration of product ions (eg, [2U-H+Mg]+ ) formed as a result of the collision induced dissociation of the respective parent ion (eg, [3Ur -H+Mg]+ ). The efficiency of gas-phase hydration of the ions [2U-H+Mg]+ and [2T-H+Mg]+ was similar. However, the efficiency of gas-phase hydration of the ion [U+Ur -H+Mg]+ was much higher than that of gas-phase hydration of the ion [T+Tdr -H+Mg]+ . On the basis of the mass spectra obtained and the performed molecular modelling, it was concluded that in the ion [T+Tdr -H+Mg]+ , we deal with a steric hindrance due to the presence of a sugar moiety, which affects water attachment. In the ion [U+Ur -H+Mg]+ , the position of the sugar moiety does not affect water attachment.

Unexpected cytosine-AuCl4- interaction under electrospray ionization mass spectrometry conditions-Formation of cytosine-Au(I) complexes.

The interaction of cytosine with AuCl4-, under electrospray ionization mass spectrometric conditions, is discussed. On the basis of respective full scan mass spectra and product ion spectra, obtained in positive and negative ion mode, it has been deduced that cytosine is very prone to form Au(I)-containing complexes. The complexes may be formed in the gas phase by decomposition of Au(III)-containing complexes and also in the electrospray ionization source as a result of the occurrence of redox process. It has also been found that the interaction of cytosine with Au+ is stronger than that with Cu+ or Ag+, although taking into account the electrostatic attraction, it is not expected.

Comparison of the electrospray ionization (ESI) responses of penicillins with ESI responses of their methanolysis products.

The electrospray ionization (ESI) responses, defined as the area of chromatographic peak of ion [M+H]+ obtained upon HPLC/ESI-MS analysis, of three ß-lactam antibiotics, namely penicillin G, ampicillin and carbenicillin have been compared with the ESI responses of their methanolysis products. It has been found that methanolyzed penicillin G has much higher ESI response than the penicillin G. Methanolyzed ampicillin also has higher ESI response than ampicillin; however, the effect is less pronounced than for penicillin. Methanolyzed carbenicillin does not have pronouncedly higher ESI response than carbenicillin.

Detection of the iron complexes with hydrolysis products of cephalexin and cefradine upon high-performance liquid chromatography/electrospray ionization mass spectrometry analysis.

RATIONALE: Cephalosporins (e.g. cephalexin, cefradine) are a major group of widely used ß-lactam antibiotics. Hydrolysis of the ß-lactam ring is an important reaction (often undesired) which leads to deactivation of ß-lactams. To the best of our knowledge there is no electrospray ionization mass spectrometry (ESI-MS) data reported concerning the products of hydrolysis of cephalosporins. METHODS: The hydrolysis of cephalexin and cefradine was performed in aqueous NaOH solutions. After the process the solutions were analyzed by high-performance liquid chromatography (HPLC)/ESI-MS. The elemental compositions of the ions discussed were confirmed by the accurate mass measurements on a quadrupole time-of-flight (QTOF) mass spectrometer. RESULTS: Unexpectedly, complexes between the hydrolysis products of cephalexin and cefradine (CFLh and CFRh ) and iron cation were detected upon HPLC/ESI-MS analysis, namely the ions [(CFLh -H)2 +Fe]+ and [(CFRh -H)2 +Fe]+ , although iron was not added to the analyzed solutions or to the mobile phase. These ions were found to be very stable in the gas phase. CONCLUSIONS: The detection of the complexes between the hydrolysis products of cephalosporins and iron may have a positive impact on the sensitivity and specificity of HPLC/ESI-MS analyses of the hydrolysis products of some cephalosporins.

Gas-phase relative stabilities of Tl+-crown ether complexes and Rb+-crown ether complexes.

The gas-phase stabilities of Tl+-crown ether complexes and Rb+-crown ether complexes were studied using the electrospray ionization-collision-induced dissociation-tandem mass spectrometry. Tl+ and Rb+ have identical ionic radii, thus a comparison of the properties of the crown ether complexes with these two cations seems to be justified. The selected crown ethers were 12C4 (it has a cavity smaller than the cation radius), 18C6 (it has a cavity of size similar to the cation radius), 24C8 (it has a cavity greater than the cation radius) and their conjugates. It has been found that the crown ether complexes of stoichiometry 1:1 with Tl+ are more or equally stable in the gas phase than the crown ether complexes with Rb+. However, 2:1 complexes with Tl+ are less stable than the complexes with Rb+.

Electrospray ionization mass spectrometric study of thallium complexes with nucleosides.

The complexes between Tl+, K+, and nucleosides were studied by using electrospray ionization mass spectrometry. It was found that for complexes of 1:1 stoichiometry, thallium complexes with cytidine were the most abundant and thallium complexes with guanosine were the second most abundant ones. The relative abundances of cytidine-Tl+ to cytidine-K+ complexes depended on stoichiometry (at higher stoichiometry the potassium complexes were more abundant). In other words, the relative affinity of Tl+ and K+ to form cytidine complexes depends on the stoichiometry of the formed complexes. Guanosine-Tl+ complexes were more abundant than guanosine-K+ complexes, irrespective of stoichiometry. Both guanosine tetramer and mixed cytidine/guanosine tetramer were more abundant when they were stabilized by thallium than potassium. Therefore, Tl+ may affect the K+ stabilization of these tetramers.

Electrospray ionization-collision-induced dissociation-tandem mass spectrometry study of lead complexes with deprotonated nucleobases.

The complexes between the lead cation and deprotonated nucleobases (and deprotonated nucleosides) are studied by using electrospray ionization-collision-induced dissociation-tandem mass spectrometry. It has been found that the deprotonated N9 atom is not the site of lead cation attachment. In ions [A - H + Pb]+ and [C - H + Pb]+, the lead cation is coordinated by the adenine N1 atom and cytosine  N3 atom and interaction between the lead cation and deprotonated amino groups seems very likely. Deprotonated thymine shows a higher affinity toward lead cation than deprotonated uracil. In the lead-nucleoside complexes lead cation interacts with a sugar moiety.

UNUSUALLY STABLE ADDUCT BETWEEN METHANOLYZED AMOXICILLIN OR AMPICILLIN AND THEIR DIKETOPIPERAZINE DERIVATIVES.

Amoxicillin and ampicillin were subjected to methanolysis. As expected, the methanolysis products were observed by HPLC-ESI-MS. Besides these products, diketopiperazine derivatives were also detected. Additionally, unusually stable adduct formed between the products of methanolysis and diketopiperazine derivatives was also identified. Analogical adducts were detected when ethanolysis was performed instead of methanolysis. HPLC-ESI-MS analysis of the separated adducts confirmed that the adducts were composed of methanolysis products and diketopiperazine derivatives.