Acid Heterodimer Research Articles

Detailed LC-UV-MS quantification of native and oxidized phenolic compounds in experimental and commercial apple juices revealed highly contrasting compositions

During apple juice production, phenolic compounds undergo enzymatic oxidation leading to newly formed molecules. More quantitative information is needed concerning these oxidized phenolic compounds (OP) that contribute to the organoleptic and nutritional properties of apple juices. Firstly, a new HPLC-UV-MS method was developed to simultaneously quantify native phenolic compounds and two families of OP (i.e. 5-O-caffeoylquinic acid dehydrodimers and epicatechin-5-O-caffeoylquinic acid heterodimers). Secondly, the method was applied to 54 commercial and experimental apple juices. Then, statistical cluster analysis (Euclidian Ward’s method) was performed on all the phenolic compound data sets. To the best of our knowledge, it is the first time that two families of OP have been successfully quantified in a large series of apple juices revealing that they may represent up to 14% of the total phenolic compounds quantified (TPQ). Furthermore, the statistical classification of the juices based on their native and oxidized polyphenol compositions clearly underlined the great discrepancies in polyphenol composition observed in this panel of juices available on the French market. Interestingly, the polyphenol concentration in most of the juices made from cider apple varieties (experimental juices and local cider producers) was on average 8-fold higher than in most of the juices found in supermarkets.

Polymer Functionalized Nanoparticles in Blue Phase LC: Effect of Particle Shape

Ethylene oxide oligomers and polymers, free and tethered to gold nanoparticles, were dispersed in blue phase liquid crystals (BPLC). Gold nanospheres (AuNPs) and nanorods (AuNRs) were functionalized with thiolated ethylene oxide ligands with molecular weights ranging from 200 to 5000 g/mol. The BPLC mixture (ΔTBP ~6 °C) was based on the mesogenic acid heterodimers, n-hexylbenzoic acid (6BA) and n-trans-butylcyclohexylcarboxylic acid (4-BCHA) with the chiral dopant (R)-2-octyl 4-[4-(hexyloxy)benzoyloxy]benzoate. The lowest molecular weight oligomer lowered and widened the BP range but adding AuNPs functionalized with the same ligand had little effect. Higher concentrations or molecular weights of the ligands, free or tethered to the AuNPs, completely destabilized the BP. Mini-AuNRs functionalized with the same ligands lowered and widened the BP temperature range with longer mini-AuNRs having a larger effect. In contrast to the AuNPs, the mini-AuNRs with the higher molecular weight ligands widened rather than destabilized the BP, though the lowest MW ligand yielded the largest BP range, (ΔTBP > 13 °C). The different effects on the BP may be due to the AuNPs accumulating at singular defect sites whereas the mini-AuNRs, with diameters smaller than that of the disclination lines, can more efficiently fill in the BP defects.

Conformational Landscape of m-Anisic Acid and Its Complexes with Formic Acid.

Four conformers of m-anisic acid were observed in a supersonic expansion using Fourier transform microwave spectroscopy. These conformers correspond to different relative orientations of the acid and methoxy groups and have their planar skeletons stabilized by resonance. When formic acid was present in the jet, the spectra of four m-anisic acid-formic acid heterodimer conformers were detected. The complexes are formed from the interaction of formic acid with each of the four observed conformers of m-anisic acid through the typical acid-acid sequential cycle with a double O-H···O═C hydrogen bond interaction in a pseudo eight-membered ring arrangement. The four heterodimer forms retain the same four m-anisic acid conformational geometries and the same relative abundances of the m-anisic acid monomeric forms in the supersonic expansion. This proves that a kinetic mechanism dominates the formation of complexes in the jet.

Carbamazepine cocrystals with several aromatic carboxylic acids in different stoichiometries: Structures and solid state characterization

A series of carbamazepine cocrystals with aromatic carboxylic acids have been prepared, including (CBZ)1(DBA)1, (CBZ)2(DBA)1(CH3OH)1 (DBA = 2,3-dihydroxy benzoic acid), (CBZ)1(NA)1(H2O)1 (NA = 1-naphthoic acid) and (CBZ)1(AC)1 (AC = anthracene-9-carboxylic acid). The synthons formed in CBZ cocrystals, e.g. amide···acid heterodimer, amide···amide homodimer, and amide···acid···H2O heterosynthon have been discussed and compared with synthons in reported CBZ cocrystals in CSD. The solid state properties of these cocrystals, such as transformation, solubility and their stabilities have been discussed in the article.

Couplings Across the Vibrational Spectrum Caused by Strong Hydrogen Bonds: A Continuum 2D IR Study of the 7-Azaindole-Acetic Acid Heterodimer.

Strongly hydrogen-bonded motifs provide structural stability and can act as proton transfer relays to drive chemical processes in biological and chemical systems. However, structures with medium and strong hydrogen bonds are difficult to study due to their characteristically broad vibrational bands and large anharmonicity. This is further complicated by strong interactions between the high-frequency hydrogen-bonded vibrational modes, fingerprint modes, and low-frequency intradimer modes that modulate the hydrogen-bonding. Understanding these structures and their associated dynamics requires studying much of the vibrational spectrum. Here, mid-IR continuum spectroscopy of the cyclic 7-azaindole-acetic acid (7AI-AcOH) heterodimer reveals the vibrational relaxation dynamics and couplings of this complex hydrogen-bonded system. Within this dimer, the NH bond of 7AI exhibits a band at 3250 cm-1 caused by a medium strength hydrogen bond, while the strongly hydrogen-bonded OH modes of acetic acid exhibit a broad double-peaked vibrational feature spanning 1750 to 2750 cm-1. Transient IR and 2D IR experiments were performed using three excitation frequencies, centered on the high-frequency OH and NH modes, and probed with a mid-IR continuum to measure the spectral response from 1000 to 3500 cm-1. While the NH stretch is observed to relax in 300 fs, the strongly hydrogen-bonded OH modes relax within the time resolution of the experiment (sub-100 fs). The difference in the strength of the hydrogen bonds is also reflected in the coupling pattern in the fingerprint region observed with 2D IR spectroscopy. Here the NH is strongly coupled to fingerprint modes involving the 7AI monomer, while the OH vibrations are strongly coupled to vibrational modes across the entire dimer. Together, the results show strong coupling and rapid energy transfer across the hydrogen-bonded interface and through the structure of the 7-azaindole-acetic acid heterodimer, highlighting the need to study the full vibrational spectrum for strongly hydrogen-bonded systems.

Proton transfer in histidine-tryptophan heterodimers embedded in helium droplets.

We used cold helium droplets as nano-scale reactors to form and ionize, by electron bombardment and charge transfer, aromatic amino acid heterodimers of histidine with tryptophan, methyl-tryptophan, and indole. The molecular interaction occurring through an N-H···N hydrogen bond leads to a proton transfer from the indole group of tryptophan to the imidazole group of histidine in a radical cationic environment.

Ultrafast continuum mid-infrared spectroscopy: probing the entire vibrational spectrum in a single laser shot with femtosecond time resolution

Until now, ultrafast IR spectroscopy has been limited by the bandwidth of optical parametric amplifiers, typically 100-400 cm(-1). Here we present the first example of transient IR spectroscopy using a continuum laser source to probe the entire mid-IR region with ultrafast time resolution. The continuum source is based on focusing the fundamental, second harmonic, and third harmonic of 1 mJ, 25 fs, 800 nm pulses in air, generating ∼150 fs continuum mid-IR pulses that span the frequency range of <400 to >5000 cm(-1) or, conversely, <2 to >25 μm. We characterize the spectral and temporal properties of dicarbonylacetonato rhodium(I) in hexane. We further demonstrate the versatility of the method by measuring the very fast and broad (>1500 cm(-1)) spectral changes following IR excitation associated with the 7-azaindole-acetic acid heterodimer in carbon tetrachloride.

Calpain 10 Homology Modeling with CYGAK and Increased Lipophilicity Leads to Greater Potency and Efficacy in Cells

Calpain 10 is a ubiquitously expressed mitochondrial and cytosolic Ca(2+)-regulated cysteine protease in which overexpression or knockdown leads to mitochondrial dysfunction and cell death. We previously identified a potent and specific calpain 10 peptide inhibitor (CYGAK), but it was not efficacious in cells. Therefore, we created a homology model using the calpain 10 amino acid sequence and calpain 1 3-D structure and docked CYGAK in the active site. Using this model we modified the inhibitor to improve potency 2-fold (CYGAbuK). To increase cellular efficacy, we created CYGAK-S-phenyl-oleic acid heterodimers. Using renal mitochondrial matrix CYGAK, CYGAK-OC, and CYGAK-ON had IC(50)'s of 70, 90, and 875 nM, respectively. Using isolated whole renal mitochondria CYGAK, CYGAK-OC, and CYGAK-ON had IC(50)'s of 95, 196, and >10,000 nM, respectively. Using renal proximal tubular cells (RPTC) in primary culture, 30 min exposures to CYGAK-OC and CYGAbuK-OC decreased cellular calpain activity approximately 20% at 1 μM, and concentrations up to 100 μM had no additional effect. RPTC treated with 10 μM CYGAK-OC for 24 h induced accumulation of ATP synthase β and NDUFB8, two calpain 10 substrates. In summary, we used molecular modeling to improve the potency of CYGAK, while creating CYGAK-oleic acid heterodimers to improve efficacy in cells. Since calpain 10 has been implicated in type 2 diabetes and renal aging, the use of this inhibitor may contribute to elucidating the role of calpain 10 in these and other diseases.

Analysis of 50 Crystal Structures Containing Carbamazepine Using the Materials Module of Mercury CSD

A set of 50 crystal structures containing the molecule carbamazepine (CBZ) have been analyzed using the Materials module within Mercury CSD 2.0. The similarity relationships between all 50 structures were determined based on the analysis of packing motifs. Packing motifs that define the similarity relationships within three separate groups of structures were found to be exclusive to a particular group. The carboxamide homodimer found in all four of the carbamazepine polymorphs is seen to be disfavored compared to the carboxamide−carboxylic acid heterodimer when a coformer molecule with a carboxylic acid group is present. Etter’s rules are found to be broken in a large percentage of the CBZ structures (24%) compared to the overall CSD statistics (2.5%), apparently due to steric hindrance caused by the dibenzazepine group. A group of 14 similar structures has been identified containing ordered or disordered coformer-filled channels. Thirteen new crystal structures containing CBZ and pharmaceutically relevan...

Transcriptional repression by the thyroid hormone receptor: function of corepressor complexes

Purpose of review Thyroid hormone receptors form heterodimers with the receptor for 9-cis-retinoic acid and bind to thyroid response elements in the promoters of target genes. In the absence of thyroid hormone, the thyroid hormone receptor/receptor for 9-cis-retinoic acid heterodimer represses transcription through the recruitment of large multiple subunit corepressor complexes containing histone deacetylase activity. On ligand binding, thyroid hormone receptor/receptor for 9-cis-retinoic acid releases the corepressor complexes and recruits coactivator complexes. This review focuses on the nature of the corepressor complexes that associate with thyroid hormone receptor and how they function to repress transcription. Recent findings Several corepressor complexes have been implicated in repression by the “unliganded” thyroid hormone receptor (apo-thyroid hormone receptor), including the histone deacetylase-1/2-containing Sin3 and Mi2/NuRD and the histone deacetylase-3-containing nuclear receptor corepressor (N-CoR) and silencing mediator for retinoid and thyroid hormone receptors (SMRT). Previously it was thought that N-CoR and SMRT recruit histone deacetylase activity by associating with Sin3; however, it is now clear that N-CoR and SMRT are a distinct class of corepressor complexes containing histone deacetylase-3. SMRT and N-CoR potentiate the enzymatic activity of histone deacetylase-3 through direct binding. Recent studies also reveal an essential role for histone binding subunits in targeting SMRT and N-CoR complexes to chromatin. Several reports indicate that thyroid hormone receptor-β preferentially interacts with N-CoR, whereas thyroid hormone receptor-α recruits both N-CoR and SMRT. Finally, it has recently been shown that repression by thyroid hormone receptor involves methylation of histone H3 lysine 9. Summary Repression by apo-thyroid hormone receptor is a complicated process that may involve many cofactor complexes. The many corepressors involved may allow the apo-thyroid hormone receptor a good degree of flexibility in transcriptional repression. All the corepressors for thyroid hormone receptor appear to associate with histone deacetylase activity; therefore, histone deacetylation is the major mechanism through which apo-thyroid hormone receptor represses transcription.

Isolation and characterization of 1 : 1 crystalline substituted benzoic acid heterodimers resulting from intermolecular hydrogen bonding

Elighteen crystalline benzoic acid heterodimers have been prepared for the first time and characterized by elemental analyses, 1H n.m.r. and i.r. spectra, m.p./composition phase studies, and X-ray powder diffraction.

Influence of carboxylic acid association upon the lactim–lactam tautomeric equilibrium of 2-hydroxypyridines

I.r. and u.v. absorption spectroscopy in CCl4 at room temperature provides evidence for lactim–acid and lactam–acid heterodimer formation in 6-chloro-2-hydroxypyridine–acetic acid mixtures. Measurements of association constants for two types of 1:1 hydrogen-bonded complexes reveal preferential association with the lactam tautomer, leading to a shift in the apparent tautomeric equilibrium constant. These results suggest that specific interactions are of great importance in understanding solvent effects on protomeric equilibria.