Non-cyclic Analogues Research Articles

Catalytic specificity exhibited by p-sulfonatocalix[n]arenes in the methanolysis of N-acetyl-l-amino acids.

Specific acid catalysis of p-sulfonatocalix[n]arenes (n = 4, Calix-S4; n = 6, Calix-S6; n = 8, Calix-S8) was observed in the alcoholysis of N-acetyl-l-amino acids in methanol. The methanolysis rates of basic amino acid substrates (His, Lys, and Arg) were markedly enhanced in the presence of Calix-Sn, as compared with rates observed with p-hydroxybenzenesulfonic acid (pHBS), which is a noncyclic analogue of Calix-Sn. This catalytic effect of Calix-Sn was not observed for the methanolysis of Phe, Tyr, and Trp substrates. On the other hand, (1)H NMR experiments following the effect of Calix-Sn on N-acetyl-l-amino acid substrates in CD(3)OD showed that the spectrum of a mixture of the His substrate with Calix-Sn was significantly different from the combined spectra of the respective compounds. These changes in spectra support the formation of an inclusion complex of Calix-Sn with basic amino acids. Furthermore, it was obvious that methanolysis of the His substrate catalyzed by Calix-S4 and Calix-S6 obeyed Michaelis-Menten kinetics. These results indicate that the catalytic activity of Calix-Sn originates from its forming a complex with specific substrates (basic amino acids), similar to enzymatic reactions.

Relationships between basicity, structure, chemical shift and the charge distribution in resonance-stabilized iminoaminesElectronic supplementary information (ESI) available: energies and N⋯N distances in geometry-optimised iminoamine bases. See http://www.rsc.org/suppdata/p2/b2/b200899h/

Taking formamidine (gas phase proton affinity ≈950 kJ mol−1) and guanidine (gas phase proton affintiy ≈990 kJ mol−1) as the prototype iminoamines with resonance-stabilized cations, similar non-cyclic analogs based on a conjugated carbon atom backbone are studied computationally. A simple model of the charge delocalization is developed which predicts theoretical maximum gas-phase proton affinties (PAs) of ≈1114 kJ mol−1 (unbranched), 1154 kJ mol−1 (singly-branched) and 1209 kJ mol−1 (doubly-branched) for such systems. It is also shown that the 1H and 15N chemical shifts of the protons and nitrogens in the imine functions correlate both with basicity and with atoms-in-molecules multipole moments. The properties of these and related compounds are discussed in the context of proton sponges or superbases.

Synthesis and photochromism of spirobenzopyrans and spirobenzothiapyran derivatives bearing monoazathiacrown ethers and noncyclic analogues in the presence of metal ions.

Spirobenzopyrans bearing monoazathiacrown ethers and noncyclic analogues were synthesized, and their ion-responsive photochromism depending on the dual metal ion interaction with the crown ether and the phenolate anion moieties was examined using alkali and alkaline-earth metal ions, Ag(+), Tl(+), Pb(2+), Hg(2+), and Zn(2+). The prepared spirobenzopyrans showed a selective binding ability to Mg(2+) and Ag(+) with negative and positive photochromism, respectively. Among the metal ions, only Ag(+) facilitated photoisomerization to the corresponding merocyanine form. Depending on the ring size of the monoazathiacrown ether moieties, soft metal ions such as Hg(2+) and Ag(+) showed significant shifts in the UV-vis absorption spectra, while hard metal ions such as Mg(2+), Zn(2+), and Pb(2+) did not afford any meaningful shift. This result reflects that the monoazathiacrown ether and phenolate anion moieties prefer soft and hard metal ions, respectively. Therefore, the Mg(2+) and Ag(+) selectivities are mainly derived from the phenolate anion and monoazathiacrown ether moieties, respectively. On the other hand, a spirobenzothiapyran bearing 3,9-dithia-6-monoazaundecane showed a remarkable selectivity to Ag(+).

Direct Quantitative Estimation of the Macrocyclic Effect in the Dissociation of Protoporphyrin Complexes

(Chloro)platinum(III)protoporphyrin and its closest noncyclic analogue, platinum(III)biliverdin, are synthesized; the forms and stability of the complexes in proton-donating solutions as dependent on temperature and solvent composition are studied. The macrocyclic effect (the effect of coordinated macrocyclic ligand opening) is directly estimated quantitatively; a correlation between its contribution to the rate of dissociation (or stability) of the complexes and their structures is found.

1-Boraadamantane: reactivity towards mono-1-alkynyltin, -germanium and -silicon compounds — synthesis of 4-methylene-3-borahomoadamantanes

The reaction of 1-boraadamantane 1 with 1-alkynyltin ( 3), -germanium ( 4), and -silicon compounds ( 5) leads to enlargement of the tricyclic system by formation of 4-methylene-3-borahomoadamantanes ( 6– 9). These are 1,1-organoboration reactions which proceed by cleavage of the MC bond (M=Sn, Ge, Si). There is evidence for 1,1-deorganoboration which apparently take place much more readily than for non-cyclic analogues, most likely as the result of the strained tricyclic system. When 2-ethyl-1-boraadamantane ( 2) is used, again 3-borahomoadamantanes are formed, the isomers 15– 18. The product distribution is sensitive to steric effects. However, it appears that the BC(H)Et bond in 2 is slightly more reactive than the BCH 2 bonds. All products were characterised by 1H-, 11B-, 13C-, 29Si- and 119Sn-NMR.

Catalytic specificity of p-sulfonatocalix[n]arenes on the alcoholysis of N-Ac-l-amino acids in methanol solution

The specific acid catalysis of p-sulfonatocalix[n]arenes (n=4:Calix-S4, n=6:Calix-S6, n=8:Calix-S8) was observed in the alcoholysis of N-Ac-l-amino acids in methanol. With respect to the alcoholysis of Ala, His, Phe, Trp and Tyr substrates, the alcoholysis-rate of N-Ac-l-His-OH was markedly enhanced in the presence of Calix-SN as compared with that in the presence of p-hydroxybenzenesulfonic acid (pHBS), which is a noncyclic analogue of Calix-SN. Furthermore, in relation to 1H NMR results of N-Ac-l-amino acids and Calix-SN in CD3OD, it was found that the spectrum of the mixture of N-Ac-l-His-OH and Calix-S4 was significantly different from the combined spectra of the respective compounds. These changes in spectra support the formation of inclusion complex of Calix-S4 and N-Ac-l-His-OH. The above results seem to indicate that the catalytic specificity of Calix-SN is originated from the complexation with N-Ac-l-His-OH

Noncyclic geometric phase and its non-Abelian generalization

We use the theory of dynamical invariants to yield a simple derivation of noncyclic analogues of the Abelian and non-Abelian geometric phases. This derivation relies only on the principle of gauge invariance and elucidates the existing definitions of the Abelian noncyclic geometric phase. We also discuss the adiabatic limit of the noncyclic geometric phase and compute the adiabatic non-Abelian noncyclic geometric phase for a spin-1 magnetic (or electric) quadrupole interacting with a precessing magnetic (electric) field.

Crystal structure of 1,3-di-2-[(4-methoxyphenyl)-1-diazenyl]imidazolidine

The crystal and molecular structure of 1,3-di-2-[(4-methoxyphenyl)-1-diazenyl]imidazolidine (1) has been determined by single crystal X-ray diffraction analysis. This novel bis-triazene assumes a close-to planar structure with the aryltriazene moieties aligned in diametrically opposed directions, unlike many other previously reported bis-triazenes, which assume a folded structure. The structure of 1 is compared with the closely related, non-cyclic bis-triazene analogue (2), and also compared with the structure of the simple mono-triazene (3). Crystal data: 1 C17H20N6O2, monoclinic, space group C2/c, a = 34.948(3), b = 5.925(5), c = 8.1225(6) A, β = 100.8420(10)°, and V = 1652.0(2) A3, for Z = 4.

Thionylation of 5-alkyl-3H-furan-2-ones and their non-cyclic 4-oxoalkanoate ester analogs

We have studied thionylation of 5-R-3H-furan-2-ones and 4-oxoalkanoates using phosphorus pentasulfide and the Lawesson reagent. It was found that the structure of the reaction products dependent on the thionylating agent. Preparative methods have been developed for the synthesis of 5-R-5H- and 5-R-3H-thiophen-2-ones and 5-R-3H-furan-2-thiones.

Interaction of naproxen with alpha-cyclodextrin and its noncyclic analog maltohexaose.

To study the effect of mechanical grinding on crystallinity changes of naproxen (NAP) in mixtures with alpha-cyclodextrin (alphaCd), amorphous alphaCd, and maltohexaose (M6); and the possible formation of a pseudo-inclusion complex between NAP and M6 in aqueous solution. NAP-additive physical mixtures at 0.30, 0.18, and 0.10 mass fraction of drug were tested, after increasing grinding times, by differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). Interaction in aqueous solution was examined by phase-solubility and fluorescence analyses supported by molecular modelling. In the mixtures with each additive the fusion enthalpy per unit mass of NAP decreased and the half width at half maximum of selected X-ray diffraction peaks of NAP increased with the progress of grinding time following the loss of crystallinity of the samples. The mechanical treatment apparently did not affect the chemical integrity of the drug. Particularly active in the equimolar mixture was the best amorphizing agent, M6. Solution studies and molecular modelling confirmed M6 may have the feature of a supermolecule for NAP, which forms a 1:1 pseudo-inclusion complex that was as stable as the true inclusion complex with alphaCd. The intrinsically amorphous linear analog of aCd might be a potential amorphism-inducing agent and solubilizer for scarcely water soluble drugs.

Synthesis and Characterization of the First Cyclic Monothioether Derivative of 1,2-o-Carborane and Its Reactivity toward Phosphine Transition Metal Complexes.

The first cyclic monothioether derivative of [C(2)B(9)H(12)](-) has been synthesized from 1-(SH)-1,2-C(2)B(10)H(11). Reaction of the latter with (n)BuLi and 1,3-dibromopropane leads to 1,2-&mgr;-(S(CH(2))(3))-1,2-C(2)B(10)H(10). Partial degradation leads to [7,8-&mgr;-(S(CH(2))(3))-7,8-C(2)B(9)H(10)](-). Reaction of [7,8-&mgr;-(S(CH(2))(3))-7,8-C(2)B(9)H(10)](-) with [PdCl(2)(PRR'(2))(2)] leads to different sets of compounds depending on the nature of R and R'. If R = R' = (t)Bu, a closo compound with one vertex occupied by "[Pd(P(t)Bu(3))(2)]" is obtained. When aryl groups are present in the starting phosphine complex, the zwitterionic non-metal-containing compounds are obtained. The crystal structure of one of them has been determined, and the compound has been proven to be 7,8-&mgr;-(S(CH(2))(3))-11-PPh(3)-7,8-C(2)B(9)H(9). The reaction of [7,8-&mgr;-(S(CH(2))(3))-7,8-C(2)B(9)H(10)](-) with [RhCl(PPh(3))(3)] leads to [Rh(7,8-&mgr;-(S(CH(2))(3))-7,8-C(2)B(9)H(10))(PPh(3))(2)]. An agostic B-Hright harpoon-up Rh interaction has been produced, identified by a (1)H{(11)B} NMR resonance at -4.78 ppm. In this instance the cluster is connected to "Rh" via the thioether and B(11)-H. The reaction of [7,8-&mgr;-(S(CH(2))(3))-7,8-C(2)B(9)H(10)](-) with [RuCl(2)(PPh(3))(3)] leads to a compound with two B-Hright harpoon-up Ru interactions. Contrarily to its noncyclic analogues, it seems that only one isomer has been obtained.

Interactions between naproxen and maltoheptaose, the non-cyclic analog of?-cyclodextrin

The crystallinity of naproxen in solid combinations with amorphous maltoheptaose, the non-cyclic analog of β-cyclodextrin, was assessed using differential scanning calorimetry supported by X-ray powder diffractometry. Cogrinding induced a decrease in drug crystalinity to an extent which depended on the grinding time, and was most pronounced for the combination of equimolecular composition. Thermal analysis showed that the mechanism behind the conversion of crystalline naproxen into the amorphous state by cogrinding with maltoheptaose differed from that with randomly substituted, amorphous β-cyclodextrins. Interactions of naproxen with maltoheptaose in aqueous solution were studied by means of fluorescence spectroscopy, phase-solubility analysis, and computeraided molecular modelling. Maltoheptaose can wrap up naproxen, taking on a cyclic conformation and forming a ‘pseudo’ inclusion complex (apparent binding constant K1: 1 = 1.0 × 103 (−20%) L mol−1 at 25 °C) which is about as stable as the true inclusion complex with β-cyclodextrin in the lowest temperature range (0-100 K). A better complexing ability for naproxen in terms of binding constant values, however, was displayed by both native and derivatized β-cyclodextrins, the ‘hosts’ with covalently-bound cyclic structures.

Peptide mimics of glycylproline as inhibitors of prolidase

Aminoketone 1, a ψ[COCH] dipeptide mimic of glycylproline, is a potent, competitive inhibitor (K i = 270 ± 24 nM) of porcine kidney prolidase, a Mn(II)-dependent dipeptidase, whereas the homologous aminoketone 2 and its non-cyclic analogue δ-amino-levulinic acid, 3, are significantly less inhibitory (K i ≈ 1 mM).

Chalcogeno-substituierte Triphenylmethylium-Ionen vom inversen Malachitgrün-Typ / Chalcogeno-Substituted Bis-triphenylmethylium Ions of the Inverse Malachite Green Type

The longest wavelength VIS absorptions of the deeply colored CF3CO,H solutions of the 4,4′-chalcogenobis-(triphenylmethylium) ions 4++, Y[C6H4C(C6H5)2]2 (Y = O,S,Se,Te) resemble closely those of the corresponding monocationic 4-arylchalcogenotriphenylmethylium systems 5+, ArYC6H4C(C6H5)2, and not those of the structurally directly related 4,4′-bis(arylchalcogeno)triphenylmethylium ions 3+, C6H5C(C6H4YAr)2. This is in striking contrast to the results obtained previously for analogous nitrogen systems, where “inverse”, 2++, RN[C6H4C(C6H5)2], and “conventional” malachite green systems 1+, (Ar2NC6H4)2CR, yield almost indentical Amax values. A rationalization of these observations can be achieved based on the assumption of largely delocalized dications 2++ versus more or less orthogonal “double monocationic” systems 4B++ separated due to torsional twist. Whereas the formal push-pull systems 6+, ArSC6H4YC6H4C(C6H5)2 (Y = O,S,Se) behaved practically like the corresponding standard systems 5+, the mono- and bis-triphenylmethylio-substituted dibenzofurane, dibenzothiophene and thioxanthene derivatives 8+, 9++, 10+ and 11++ displayed hypsocromic shifts of their color bands relative to their noncyclic analogues which are only partly in accordance with predictions based on a simple frontier orbital Hückel model. The 1H and 13C NMR spectra of all these cationic species comply with their respective charges.

Synthesis and biological activity of new conformationally restricted analogues of pepstatin.

A new statine derivative, 3-hydroxy-4-amino-5-mercaptopentanoic acid; cysteinylstatine (CySta), was synthesized and used to prepare a series of conformationally restricted analogues of pepstatin (Iva-Val-Val-Sta-Ala-Sta) in which the conformational constraint was introduced via a bis-sulfide connecting the appropriately substituted residues in the P1 and the P3 inhibitor side chains. The precursor peptide, Iva-Cys-Val-CySta-Ala-Iaa, was synthesized and alkylated with a series of dibromoalkanes and alkenes to produce the cyclic structures. This strategy permitted the carbon atom spacing between the P1 and the P3 inhibitor side chains to be systematically varied so as to produce inhibitors with 15-, 16-, and 17-membered ring systems. Additional non-cyclic analogues were synthesized as controls by alkylating the bisthiol intermediates with methyl iodide. The inhibitory potency of the analogues were determined against porcine pepsin and penicillopepsin by using standard enzyme kinetic assays. The cyclic inhibitor were found to be potent inhibitors of both aspartic proteases; inhibitor that contained a trans-2-butene link between the two sulfur atoms was found to be the most potent inhibitor with a Ki less than 1 nM against pepsin and 3.94 nM against penicillopepsin. This series of compounds illustrates a new type of conformational restriction that can be used to probe for the bioactive conformation of peptides.

Methylxanthines reversibly inhibit tracheary-element differentiation in suspension cultures of Zinnia elegans L.

Tracheary-element (TE) differentiation in suspension-cultured mesophyll cells of Zinnia elegans L. was completely inhibited by caffeine and theophylline only when these methylxanthines were applied at least 8 h prior to the appearance of secondary cell-wall thickenings. In contrast, the calcium-channel blocker nifedipine completely inhibited TE differentiation when applied only 2-3 h prior to the onset of secondary cell-wall deposition. This indicates the involvement of a methylxanthine-inhibitable event in TE differentiation that is distinguishable from an event dependent on influx of extracellular calcium. The correlation between the time of appearance of chlorotetracycline fluorescence (an indicator of sequestered Ca(2+)) and loss of methylxanthine effectiveness indicates that inhibition by methylxanthines may result from release of Ca(2+) from intracellular stores. Methylxanthines with high potencies against adenosine 3' ∶ 5'-cyclic monophosphate (cAMP) phosphodiesterase and adenosine receptors were less effective inhibitors of TE differentiation, indicating that inhibition of differentiation by methylxanthines is independent of cAMP metabolism. The role of cAMP in transduction of the cytokinin signal, which was proposed previously on the basis of stimulation of TE differentiation by theophylline, was investigated using the non-hydrolyzable analog 8-bromo-cAMP. Although 8-bromo-cAMP stimulated differentiation in the absence of inductive concentrations of cytokinin, the non-cyclic analog 8-bromo-AMP was even more effective, indicating that 8-bromo-cAMP behaves as a cytokinin analog, rather than a second messenger, in stimulating TE differentiation.

Kinetic studies of calixarene-based cyclic and non-cyclic ‘super-uranophiles’

The kinetic parameters for the binding of UO22+ to calixarene-based ‘super-uranophiles’, para-sulphonatocalix[n]arenes (n= 5, 6 and 8: 1n) and their non-cyclic analogue, 3,5-bis{[2-hydroxy-3-(2-hydroxy-3-methyl-5-sulphonatophenyl)methyl-5-sulphonatophenyl]methyl}-4-hydroxybenzene-sulphonate (2) have been evaluated at 25 °C and pH 10.40. The reaction of UO22+ and 2 is speeded up by a factor of 85 compared to that of UO22+ and 16.

Studies on Cation Selectivities of Some Pyridine-Based Ionophores for Use in Polymer Membrane Chemical Sensors

The synthesis of some macrocyclic compounds based on 4-octyloxypyridine-2,6-dicarboxylic acid, containing sulfur and/or oxygen atoms in the 2 to 6-bridging unit, along with some non-cyclic analogues is reported. These were tested for cation selectivity in poly(vinyl chloride)-based membrane electrodes. Little selectivity was found for any ion with the oxygen-containing compounds, and none approached the selectivity for potassium reported previously for a related compound. High bonding affinities for class b acceptors, particularly Ag+ and Hg2+, were found for sulfur-containing compounds. The complexation with Hg2+ was so strong that the electrodes showed behaviour characteristic of an anion response.

“pKa” of Calixarenes and Analogs in Nonaqueous Solvents

Abstract The acid dissociation constants (Kapp) of p-t-butylcalix[n]arenes (1n: n=4, 6, and 8), O-methylated p-t-butylcalix[4]arene (2Men), and their noncyclic analogs (3n) were estimated in THF at 25°C. As pH indicators, Et4N+ salts of p-nitrophenolate, 2,4-dinitrophenolate, and picrate were employed. The pKapp values for 1n were lowered by at least four pK units from that of p-t-butylphenol because of strong intramolecular hydrogen-bonding interactions. Compounds 2n involved both the strong and weak hydrogen bonds: the proton in the strong hydrogen bond showed the acidity comparable with that of 1n whereas that in the weak hydrogen bond showed the relatively high pKapp. These properties were discussed in relation to δOH (chemical shift in 1HNMR) and νOH(OH vibration band in IR). This is the first systematic discussion on “pKa” of p-t-butylcalix[n]arenes.

Electrochemical reduction and structural properties of borylphosphinoethene derivatives

The intramolecular coordination bonds between phosphoryl-, thio-, and selenophosphoryl groups and boron facilitate the electrochemical reduction of borylphosphinoethene derivatives as compared with their noncyclic analogs. In 1-dibutylboryl-2-diphenylphosphino-1-butyl-2-phenylethene reception of the first electron takes place in the C=C bond. In the oxide, sulfide, and selenide, the electron-accepting centers are most likely the P-C1 and P=R (R=S, Se) bonds.