Reactivity profiles of ligands of mammalian retinoic acid receptors: a preliminary COREPA analysis

Retinoic acid and associated derivatives comprise a class of endogenous hormones that bind to and activate different families of retinoic acid receptors (RARs, RXRs), and control many aspects of vertebrate development. Identification of potential RAR and RXR ligands is of interest both from a pharmaceutical and toxicological perspective. The recently developed COREPA (COmmon REactivity PAttern) algorithm was used to establish reactivity profiles for a limited data set of retinoid receptor ligands in terms of activation of three RARs (alpha, beta, gamma) and an RXR (alpha). Conformational analysis of a training set of retinoids and related analogues in terms of thermodynamic stability of conformers and rotational barriers showed that these chemicals tend to be quite flexible. This flexibility, and the observation that relatively small energy differences between conformers can result in significant variations in electronic structure, highlighted the necessity of considering all energetically reasonable conformers in defining common reactivity profiles. The derived reactivity patterns for three different subclasses of the RAR (alpha, beta, gamma) were similar in terms of their global electrophilicity (nucleophilicity) and steric parameters. However, the profile of active chemicals with respect to interaction with the RXR-alpha differed qualitatively from that of the RARs. Variations in reactivity profiles for the RAR versus RXR families would be consistent with established differences in their affinity for endogenous retinoids, likely reflecting functional differences in the receptors.     

A dinitrophenylation method for the micro-determination of amide nitrogen

A new micro-method is reported for the determination of amide nitrogen, based on the estimation of 2,4-dinitroaniline produced by the reaction between ammonia, quantitatively liberated from the protein, and 1-fluoro-2,4-dinitrobenzene. Application of the method to 0.5-mg samples of wool gives results in agreement with those obtained by other authors for the same type of wool. Analyses of cuticle-rich material obtained from these wool samples show that in one sample out of three the cuticle is significantly poorer in amide groups than the whole fibre The mean standard error taken over all the analyses is 4 5 %.     

Determination of Aqueous Nickel-Carbonate and Nickel-Oxalate Complexation Constants

An ion-exchange method was used to determine complexation constants for the Ni-oxalate and Ni-carbonate systems in a NaClO₄ background electrolyte. The Ni-oxalate data were interpreted in terms of a single Niox(aq) complex having log K ₁ values for Ni²⁺ + ox^2– Niox(aq) of 3.9 ± 0.1 (I.S. = 0.5 mol-L^–1 p[H] = 7.1) and 4.4 ± 0.1 (I.S. = 0.1 mol-L^–1 p[H] = 8.6) at 22 ± 1C. Specific ion-interaction theory (SIT) was used to obtain log K ₁ = 5.17 ± 0.05 (95% confidence level and = –0.23 ± 0.15) at I.S. = 0. The Ni-carbonate studies were carried out at p[H] values of 7.5, 8.5, and 9.6 in 0.5 mol-L^–1 NaClO₄/NaHCO₃ solutions. The NiCO₃(aq) species was the dominant complex in the [CO₃ ^2–] concentration ranges studied at all three p[H] values. A log K ₁ value for Ni²⁺ + CO₃ ^2– NiCO₃(aq) of 2.9 ± 0.3 was deduced at I.S. = 0.5 mol-L^–1. Extrapolating this value to zero ionic strength using the SIT approach yielded log K ₁ = 4.2 ± 0.3 (95% confidence level and = –0.26 ± 0.04). The data allowed upper bound values for the complexation constants for NiHCO₃ ⁺ and Ni(CO₃)₂ ^2– to be estimated, i.e., log K < 1.4 for Ni²⁺ + HCO₃ ^– NiHCO₃ ⁺, and log K ₂ < 2 for NiCO₃(aq) + CO₃ ^2– Ni(CO₃)₂ ^2–, respectively.     

Reactions of metal ions with dithizone in molten naphthalene

A comparative study has been made of the reactions of metal ions with dithizone in the two media, chloroform and molten naphthalene. The absorption spectra of several metal dithizonates, prepared in molten naphthalene, were recorded and were found to be the same as those of the dithizonates obtained by extraction of metal ions from aqueous solution with chloroform dithizone.     

Reactivity profiles of ligands of mammalian retinoic acid receptors: A preliminary COREPA analysis

Retinoic acid and associated derivatives comprise a class of endogenous hormones that bind to and activate different families of retinoic acid receptors (RARs, RXRs), and control many aspects of vertebrate development. Identification of potential RAR and RXR ligands is of interest both from a pharmaceutical and toxicological perspective. The recently developed COREPA (COmmon REactivity PAttern) algorithm was used to establish reactivity profiles for a limited data set of retinoid receptor ligands in terms of activation of three RARs ( f , g , n ) and an RXR ( f ). Conformational analysis of a training set of retinoids and related analogues in terms of thermodynamic stability of conformers and rotational barriers showed that these chemicals tend to be quite flexible. This flexibility, and the observation that relatively small energy differences between conformers can result in significant variations in electronic structure, highlighted the necessity of considering all energetically reasonable conformers in defining common reactivity profiles. The derived reactivity patterns for three different subclasses of the RAR ( f , g , n ) were similar in terms of their global electrophilicity (nucleophilicity) and steric parameters. However, the profile of active chemicals with respect to interaction with the RXR- f differed qualitatively from that of the RARs. Variations in reactivity profiles for the RAR versus RXR families would be consistent with established differences in their affinity for endogenous retinoids, likely reflecting functional differences in the receptors.     

Bestimmung des Schwefels in Steinkohle und Cokes

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