Supramolecular Nature of Multicomponent Crystals Formed from 2,2'-Thiodiacetic Acid with 2,6-Diaminopurine or N9-(2-Hydroxyethyl)adenine.

The synthesis and characterization of the multicomponent crystals formed by 2,2'-thiodiacetic acid (H2tda) and 2,6-diaminopurine (Hdap) or N9-(2-hydroxyethyl)adenine (9heade) are detailed in this report. These crystals exist in a salt rather than a co-crystal form, as confirmed by single crystal X-ray diffractometry, which reflects their ionic nature. This analysis confirmed proton transfer from the 2,2'-thiodiacetic acid to the basic groups of the coformers. The new multicomponent crystals have molecular formulas [(H9heade+)(Htda-)] 1 and [(H2dap+)2(tda2-)]·2H2O 2. These were also characterized using FTIR, 1H and 13C NMR and mass spectroscopies, elemental analysis, and thermogravimetric/differential scanning calorimetry (TG/DSC) analyses. In the crystal packing the ions interact with each other via O-H⋯N, O-H⋯O, N-H⋯O, and N-H⋯N hydrogen bonds, generating cyclic hydrogen-bonded motifs with graph-set notation of R22(16), R22(10), R32(10), R33(10), R22(9), R32(8), and R42(8), to form different supramolecular homo- and hetero-synthons. In addition, in the crystal packing of 2, pairs of diaminopurinium ions display a strong anti-parallel π,π-stacking interaction, characterized by short inter-centroids and interplanar distances (3.39 and 3.24 Å, respectively) and a fairly tight angle (17.5°). These assemblies were further analyzed energetically using DFT calculations, MEP surface analysis, and QTAIM characterization.

H(N3)dap (Hdap = 2,6-Diaminopurine) Recognition by Cu2(EGTA): Structure, Physical Properties, and Density Functional Theory Calculations of [Cu4(µ-EGTA)2(µ-H(N3)dap)2(H2O)2]·7H2O.

Reactions in water between the Cu2(µ-EGTA) chelate (EGTA = ethylene-bis(oxyethyleneimino)tetraacetate(4-) ion) and Hdap in molar ratios 1:1 and 1:2 yield only blue crystals of the ternary compound [Cu4(µ-EGTA)2(µ-H(N3)dap)2(H2O)2]·7H2O (1), which has been studied via single-crystal X-ray diffraction and various physical methods (thermal stability, spectral and magnetic properties), as well as DFT theoretical calculations. In the crystal, uncoordinated water is disordered. The tetranuclear complex molecule also has some irrelevant disorder in an EGTA-ethylene moiety. In the complex molecule, both bridging organic molecules act as binucleating ligands. There are two distorted five- and two six-coordinated Cu(II) centers. Each half of EGTA acts as a tripodal tetradentate Cu(II) chelator, with a mer-NO2 + O(ether, distal) conformation. Hdap exhibits the tautomer H(N3)dap, with the dissociable H-atom on its less basic N-heterocyclic atom. These features favor the efficient cooperation between Cu-N7 or Cu-N9 bonds with appropriate O-EGTA atoms, as N6-H···O or N3-H···O interligand interactions, respectively. The bridging role of both organics determines the tetranuclear dimensionality of the complex. In this crystal, such molecules associate in zig-zag chains built by alternating π-π interactions between the five- or six-atom rings of Hdap ligands of adjacent molecules. DFT theoretical calculations (using two different theoretical models and characterized by the quantum theory of "atoms in molecules") reveal the importance of these π-π interactions between Hdap ligands, as well as those corresponding to the referred hydrogen bonds in the contributed tetranuclear molecule.

Dicopper(II)-EDTA Chelate as a Bicephalic Receptor Model for a Synthetic Adenine Nucleoside.

In the extensive field of metal ions, their interactions with nucleic acids, and their constituents, the main aim of this work is to develop a metal chelate suitable to recognize two molecules of an adenine nucleoside. For this purpose, the dinuclear chelate Cu2 (µ-EDTA) (ethylenediaminetetraacetate(4-) ion (EDTA)) is chosen as a bicephalic receptor model for N9-(2-hydroxyethyl)adenine (9heade). A one-pot synthesis is reported to obtain the compound [Cu2(µ2-EDTA)(9heade)2(H2O)4]·3H2O, which has been characterized by single-crystal X-ray diffraction and various spectral, thermal, and magnetic methods. The complex unit is a centro-symmetric molecule, where each Cu (II) center is chelated by a half-EDTA, and is further surrounded by an N7-dentate 9heade nucleoside and two non-equivalent trans-O-aqua molecules. The metal chelate-nucleoside molecular recognition is referred to as an efficient cooperation between the Cu-N7(9heade) coordination bond and a (9heade)N6-H···O(carboxyl, EDTA) interligand interaction. Theoretical calculations are also made to account for the relevance of this interaction. The extreme weakness with which each water molecule binds to the metal center disturbs the thermal stability and the infrared (FT-IR) and electron spin resonance (ESR) spectra of the compound.

Covalent Immobilization of Antibodies through Tetrazine-TCO Reaction to Improve Sensitivity of ELISA Technique.

Enzyme-linked immunosorbent assay (ELISA) is routinely used to detect biomolecules related to several diseases facilitating diagnosis and monitoring of these, as well as the possibility of decreasing their mortality rate. Several methods have been carried out to improve the ELISA sensitivity through antibodies immobilization on the microtiter plates. Here, we have developed a strategy of antibodies immobilization to improve the ELISA sensitivity increasing the antibody density surface through the tetrazine (Tz)-trans-cyclooctene (TCO) reaction. For this, we prepared surfaces with tetrazine groups while the captured antibody was conjugated with TCO. The tetrazine surfaces were prepared in two different ways: (1) from aminated plates and (2) from Tz-BSA-coated plates. The surfaces were evaluated using two sandwich ELISA models, one of them using the low-affinity antibody anti-c-myc as a capture antibody to detect the c-myc-GST-IL8h recombinant protein, and the other one to detect the carcinoembryonic human protein (CEA). The sensitivity increased in both surfaces treated with tetrazine in comparison with the standard unmodified surface. The c-myc-GST-IL8h detection was around 10-fold more sensible on both tetrazine surfaces, while CEA ELISA detection increased 12-fold on surfaces coated with Tz-BSA. In conclusion, we show that it is possible to improve the ELISA sensitivity using this immobilization system, where capture antibodies bond covalently to surfaces.

Probing the effect of N-alkylation on the molecular recognition abilities of the major groove N7-binding site of purine ligands.

The study of the metal binding pattern of N-methyladenines (1-, 3-, 7- or 9-Meade) towards CuII-iminodiacetate-like chelates is addressed on the basis of XRD crystal structures of sixteen novel ternary compounds. Except for three compounds, all others feature an square-based Cu(II) coordination, type 4 + 1, and the efficient cooperation of a CuN7 bond with an intra-molecular N6-H⋯O(coord. carboxylate) interligand interaction as the major metal-binding pattern. The three referred exceptions to this behavior are: (1) the compound [Cu(MIDA)(7Meade)(H2O)]·4H2O, which evidence the CuN3 binding pattern; the (2) [Cu(IDA)(1Meade)(H2O)2]·4H2O, which molecular recognition consist in the CuN9 bond and a (distal aqua)⋯⋯N3(1Meade) intra-molecular interaction, within an octahedral Cu(II) center; and (3) [Cu(IDA)(9Meade)(H2O)2]·3H2O, also with a 4 + 1 + 1 Cu(II) coordination, where the CuN7 bond exists along with an extremely weak N6-H⋯O(coord. carboxylate) interaction (3.33 Å, 140.2°). This former interaction is determined by packing forces that promote the participation of the N6H group in a 'trifurcated' H-bond. In conclusion, the cooperation between the CuN7 bond (not possible for 7Meade) and the intra-molecular N6-H⋯O interaction is clearly favored (a) by the H-accepting role of the O-coordinated carboxylate atoms from the iminodiacetate ligands in mer-NO2 conformation and (b) in compounds where the Cu(II) atom exhibits an elongated square-base pyramidal coordination, type 4 + 1.

La dieta mediterránea y el ejercicio físico mejoran el bienestar durante la menopausia en mujeres de Almería (España) / Adherence to Mediterranean diet and physical activity improve well-being during menopause in women from Almeria (Spain)

Objetivo principal: Evaluar la sintomatología menopáusica, hábitos de vida y condiciones sociodemográficas de una muestra poblacional de mujeres entre 45 y 60 años de Almería (España), y analizar qué variables influyen en la aparición de síntomas climatéricos. Metodología: Se obtuvieron datos de 130 mujeres participantes a través de cuestionarios. La severidad de los síntomas menopáusicos se evaluó con el cuestionario Menopause Rating Scale (MRS). Resultados principales: En promedio, las mujeres postmenopáusicas presentaron mayor edad, Índice de Masa Corporal (IMC) y frecuencia de no tener pareja estable. Se observó una sintomatología total mayor (moderada), así como somático-vegetativa y urogenital en mujeres postmenopáusicas. La adherencia a la dieta mediterránea y el ejercicio físico redujeron la sintomatología somático-vegetativa y psicológica, respectivamente. Conclusión principal: Mantener hábitos de vida saludables como el ejercicio y la dieta mediterránea pueden disminuir la sintomatología menopáusica y mejorar la calidad de vida de mujeres en esta fase.(AU)

Objective: To evaluate menopause symptomatology, lifestyle habits and sociodemographic conditions of women between 45 and 60 years old in the province of Almeria (Spain), and to analyse which variables are related with the manifestation of climacteric symptoms. Methods: Data was obtained by carrying out surveys with 130 participating women. The severity of menopausal symptoms was evaluated with the Menopause Rating Scale (MRS) questionnaire. Results: On average, postmenopausal women were older, had higher Body Mass Index values, and higher frequency of not having a partner, compared with premenopausal women. Postmenopausal women had higher total symptoms, associated with higher somatic-vegetative and urogenital symptoms. Adherence to Mediterranean diet and physical exercise reduced somatic-vegetative and psychological symptoms, respectively. Conclusions: Maintaining specific healthy lifestyle habits such as Mediterranean diet and physical exercise can reduce menopause symptoms and increase the quality of life of menopausal women.(AU)

Molecular recognition between adenine or 2,6-diaminopurine and copper(II) chelates with N,O2,S-tripodal tetradentate chelators having thioether or disulfide donor groups.

Five novel ternary copper(II) complexes with the N,O2,S-tripodal tetradentate chelators N,N-bis(carboxymethyl)-S-benzylcysteaminate(2-) ion (BCBC) or N,N,N',N'-tetrakis(carboxymethyl)cystaminate(4-) ion (TCC) and adenine (Hade), 2,6-diaminopurine (Hdap), 2,2'-bipyridine (bpy) or 1,10-phenanthroline (phen) as co-ligand were synthesized and characterized by X-ray diffraction and other physical methods: [Cu2(BCBC)2(µ2-N3,N7-H(N9)ade)(H2O)2]·H2O (1), [Cu2(BCBC)2(µ2-N7,N9-H(N3)dap)(H2O)2]·4H2O (2), [Cu2(µ2-TCC)(H(N9)ade)2(H2O)2]·10H2O (3), [Cu2(µ2-TCC)(bpy)2]·15H2O (4) and [Cu2(µ2-TCC)(phen)2]·14H2O (5). The crystal structure of H4TCC·3H2O was also determined. All ternary Cu(II) complexes have molecular structures. The N-(2-mercaptoethyl)-iminodiacetate moieties of BCBC or TCC ligands play a NO2+S-tripodal tetradentate role, with the S-(thioether or disulfide) atom as the apical/distal donor of the copper(II) center. In 1-3, the iminodiacetate moiety exhibits a mer-NO2 conformation (two nearly coplanar chelate rings) while in 4 and 5 (with bpy or phen as coligand) it displays a fac-NO+O (apical/distal) conformation. We conclude that the formation of the Cu-S(thioether or disulfide) bonds is strongly favored by the N-branched topology of the S-ligands in the reported compounds.