1-adamantanecarboxylic Acid Research Articles

Novel Bradykinin Analogues Modified in the N-Terminal Part of the Molecule with a Variety of Acyl Substituents

In the current work we present some pharmacological characteristics of ten new analogues of bradykinin (Arg–Pro–Pro–Gly–Phe–Ser–Pro–Phe–Arg) modified in the N-terminal part of the molecule with a variety of acyl substituents. Of the many acylating agents used previously with B2 receptor antagonists, the following residues were chosen: 1-adamantaneacetic acid (Aaa), 1-adamantanecarboxylic acid (Aca), 4-tert-butylbenzoic acid (t-Bba), 4-aminobenzoic acid (Aba), 12-aminododecanoic acid (Adc), succinic acid (Sua), 4-hydroxybenzoic acid, 4-hydroxy-3-methoxybenzoic acid, 3-(4-hydroxyphenyl)propionic acid and 6-hydroxy-2-naphthoic acid. Biological activity of the compounds was assessed in the in vivo rat blood pressure test and the in vitro rat uterus test. Surprisingly, N-terminal substitution of the bradykinin peptide chain itself with aforementioned groups resulted in antagonists of bradykinin in the pressor test and suppressed agonistic potency in the uterotonic test. These interesting findings need further studies as they can be helpful for designing more potent B2 receptor blockers.

Synthesis and Bioactivity of Novel Adamantyl Derivatives as Potent MDR Reversal Agents

Multidrug Resistance (MDR) is a type of resistance of tumor cells to various kinds of chemotherapeutic drugs which are structurally unrelated and also one of the major impediments to chemotherapeutic treatment of cancer. It has been reported that 49 ATP-binding cassette (ABC) transporter genes are present in the human genome. Among them, over-expression of P-glycoprotein (P-gp), encoded by MDR1 gene is one of the major factors contributing to multidrug resistance which leads to barrier to successful chemotherapy. Therefore the availability of safe and potent MDR reversal agents would be beneficial for clinical use. Reversal agents can act by binding to the membrane transport protein (P-gp), by inhibiting MDR’s drug efflux capacity, or by suppressing expression of the MDR1 gene itself. Although a number of P-gp inhibitors have been developed, there is currently no clinically useful drug that inhibits P-gp. In an attempt to find new and more effective MDR reversal agents, we previously identified adamantyl derivatives exhibiting more potent MDR reversal activity than verapamil, a well-known P-gp inhibitor, without considerable intrinsic cytotoxicity. Compounds 1-2 were identified utilizing high throughput image-based DIOC2 efflux assays and anti-proliferation assays in a P-gp over-expressing MDR sarcoma cell line, MES-SA/DX5. Herein we describe a further structure-activity relationship study to find additional compounds in this series. With the objective of investigating the effect of aminebased substituents on reversal activity, we synthesized a series of adamantyl derivatives 2a-t that feature reductive amination of the adamantyl aldehyde derivatives as a key step. The synthetic procedures for 2a-t are described in Schemes 1 to 3. Synthesis of a new series of adamantyl derivatives (2a-t) were carried out starting from commercially available 3amino benzoic acid 3 (Scheme 1). The corresponding esters (4a-d) and amides (4e-g) of 3-amino benzoic acid were prepared in the next step. Further alkylation with chloroacetyl chloride resulted in the alkylated derivatives (5a-g). Bromination of 1-adamantane carboxylic acid 6 with bromine gave an intermediate 7, which was followed by Friedel-Crafts alkylation with anisole to provide compound 8, as shown in Scheme 2. Esterification of 8 resulted in compound 9, which was reacted with LiAlH4 to give an alcohol 10. The aldehyde 11 was then obtained by oxidation of alcohol 10. Demethylation of 11 was carried out by using BBr3 to afford a phenol compound 12, which was utilized as a key intermediate to prepare the final compounds. Adamantyl aldehyde 13, a precursor for the synthesis of the target adamantyl motifs (2a-n), was generated by reacting 12 with methyl 3-(2chloroacetamido) benzoate 5a. In similar fashion, the precursor 14o-t was generated by reacting 12 with 5b-g for the synthesis of derivatives 2o-t. Finally the reductive amination reaction of 13 or 14o-t with a variety of amine resulted in Pgp related MDR modulators 2a-t. Reversal activity of these derivatives was evaluated in

Ru4(CO)8(μ-OOCAd)4(PPh3)2: Phosphine Derivative of an Electron-Deficient Linear Tetraruthenium Cluster

The reaction of Ru3(CO)12 with 1-adamantanecarboxylic acid afforded a purple solid with the formulation Ru2(CO)4(μ-OOCAd)2 (Ad = 1-adamantyl). Reaction of this solid with PPh3 gave Ru4(CO)8(μ-OOCAd)4(PPh3)2, a 64-electron linear tetraruthenium cluster.

Synthesis and structure of triphenylbismuth bis(1-adamantanecarboxylate)

Triphenylbismuth bis(1-adamantanecarboxylate) was synthesized by reacting triphenylbismuth with 1-adamantanecarboxylic acid in the presence of hydrogen peroxide. In the complex, the coordination sphere of a bismuth atom is a trigonal bipyramid with C(Ph) atoms in the equatorial plane and O atoms in the apical positions. The Bi-C bond lengths are 2.213(4) A (two bonds) and 2.222(5) A; two Bi-O bond lengths are 2.306(3) A. The Bi…O(=C) donor-acceptor interactions (2.716(3) A) occur in the molecule. The equatorial CBiC angle on the side of the Bi…O(=C) contact is 157.1(2)°.

Koch–Haaf reaction of adamantanols in an acid-tolerant hastelloy-made microreactor

The Koch–Haaf reaction of adamantanols was successfully carried out in a microflow system at room temperature. By combining an acid-tolerant hastelloy-made micromixer, a PTFE tube, and a hastelloy-made microextraction unit, a packaged reaction-to-workup system was developed. By means of the present system, the multigram scale synthesis of 1-adamantanecarboxylic acid was achieved in ca. one hour operation.

Synthesis and structure of tri-m-tolylantimony bis(1-adamantanecarboxylate)

Tri(m-tolyl)antimony bis(1-adamantanecarboxylate) (3-MeC6H4)3Sb[OC(O)C10H15]2 has been synthesized with a yield of 90.0% by the reaction of tri(m-tolyl)antimony with 1-adamantanecarboxylic acid in the presence of hydrogen peroxide in ether. According to X-ray diffraction analysis data, the antimony atom has a distorted trigonal-bipyramidal coordination with the axially positioned oxygen atoms of carboxyl groups. The axial OSbO angle is 173.1(2)°; the equatorial CSbC angles are 112.0(1)°, 112.0(1)°, and 136.0(3)°; the Sb-O distance is 2.109(3)A; the Sb-C distances are 2.103(5), 2.103(5), and 2.121(7) A; intramolecular Sb…O(=C) contacts are 3.069(5) A.

A Novel Synthesis of 3-Amino-1-Adamantanemethanol

3-amino-1-adamantanemethanol was synthesized from adamantane carboxylic acid following the procedures of Ritter reaction, hydrolysis, neutralization and reduced reaction without the participation of bromine. The total yield of 3-amino-1-adamantanemethanol was 43%. The structure of the target compound was characterized by elemental analysis, IR, MS, 1HNMR,etc. In addition, the possible reaction mechanisms was proposed.

The First Synthesis of N,N,N’,N’-Tetramethyl-1, 3-Disaminomethyl- Adamantane Dihydrochloride

A new tertiary amine derivative of adamantane —N,N,N’,N’-tetramethyl-1, 3-disaminomethyl adamantane dihydrochloride (1), which is a key intermediate for preparing Gemini surfactants and bola surfactants, has been synthesized in this paper. The target compound (1) can be synthesized in high yield by using 1-adamantanecarboxylic acid as raw material. The structure of these compounds has been identified.

A novel bradykinin antagonist with improved properties

Acylation of the N-terminus of [D-Arg0, Hyp3, Thi5,8, D-Phe7] bradykinin with 1-adamantanecarboxylic acid results in an analogue with enhanced potency of at least 33-fold. The new antagonist has potential as a pharmacological tool in the investigation of the role of endogenous bradykinin in cardiovascular regulation.

The Joining of Measurement and Prediction: The Enthalpy of Formation of 1,4-Cubanedicarboxylic Acid

This study is a multidisciplinary contribution to the thermochemistry of 1,4-cubanedicarboxylic acid (pentacyclo[4.2.0.02,5.03,8.04,7]octane-1,4-dicarboxylic acid). An isoperibolic static microbomb calorimeter was used to determine the enthalpy of formation in the condensed phase at T = 298.15 K as ΔfHm°(cr) = (−355.9 ± 11.7) kJ·mol−1. The enthalpy of sublimation was obtained by combining the vaporization enthalpy evaluated by correlation-gas chromatography and the fusion enthalpy measured by differential scanning calorimetry and adjusted to T = 298.15 K, which afforded the value ΔsubHm(298.15 K) = (126.5 ± 9.0) kJ·mol−1. Combination of these two enthalpies gave ΔfHm°(g, 298.15 K) = (−229.4 ± 14.8) kJ·mol−1. Additionally the enthalpy of sublimation of 1-adamantanecarboxylic acid (tricyclo[3.3.1.13,7]decane-1-carboxylic acid) was determined as ΔsubHm(298.15 K) = (98.7 ± 4.5) kJ·mol−1. By means of theoretical calculations using isodesmic reactions, the enthalpy of formation of 2,6-cuneanedicarboxylic acid (...

Steric effects in hydrogen bonded columns of salts of benzoic acid and 1-adamantanecarboxylic acid with the cyclic amines CnH2n+1NH2, n = 5, 6, 7, 8 and 12

The hydrogen bonded columns of salts of benzoic acid or adamantanecarboxylic acid and five cyclic amines are reported. During solution crystallization, the H from the carboxylic acid transfers to the amine to form ammonium carboxylate salts which feature three charge-separated N+–H⋯O−hydrogen bonds to form two types of 1-D hydrogen bonded columns. Of the ten structures, viz. (cyclopentylammonium·benzoate) (1), (cyclohexylammonium·benzoate) (2), (cyclododecylammonium·benzoate) (5), (cyclopentylammonium·adamantanecarboxylate) (6), (cyclohexylammonium·adamantanecarboxylate) (7) and (cyclododecylammonium·adamantanecarboxylate) (10) form a type IIhydrogen bonded column which consists of repeating R34(10) hydrogen bonded rings whereas (cycloheptylammonium·benzoate) (3), (cyclooctylammonium·benzoate) (4), (cycloheptylammonium·adamantanecarboxylate) (8), and (cyclooctylammonium·adamantanecarboxylate) (9) form a type IIIhydrogen bonded column, which consists of alternating R24(8)/R44(12) hydrogen bonded rings. Even with two sterically different anions, the type of hydrogen bonded column formed is the same for each counter cation and hence it is the size of the cyclic ammonium rings that influences the type of hydrogen bonded column. From this we can gather clues about the effect of the steric size of the cation and anion and its effect on the overall packing.

ChemInform Abstract: The Crystal and Molecular Structures of Adamantanecarboxylic Acid at 173 and 280 K

The crystal structure of adamantanecarboxylic acid, tricyclo[3.3.1.13,7] decan-1-carboxylic acid C10H15COOH, has been determined by X-ray diffraction at two temperatures, 173 and 280 K. At both tem...

The role of synthetic parameters in the magnetic behavior of relative large hcp Ni nanoparticles

The controllable synthesis of relatively large nickel nanoparticles via thermal decomposition of nickel acetate tetrahydrate in oleylamine in the presence of 1-adamantane carboxylic acid (ACA) and trioctylphosphine oxide (TOPO) is reported. High crystalline hcp nanoparticles of different sizes have been prepared at 290 °C, whereas at relative lower temperatures fcc are favored. The particle size was varying between 50 and 150 nm by properly adjusting the proportion of the capping ligands. TOPO-to-ACA ratio was also found to have an influence on the magnetic properties through the potential formation of a NiO shell. Pure hcp Ni nanoparticles over 50 nm in size served as models to illuminate the magnetic behavior of this metastable hexagonal Ni phase. Contrary to the net ferromagnetic characteristics of fcc Ni nanoparticles in the same size range, hexagonal structured particles exhibit superparamagnetic behavior at room temperature and a weak ferromagnetic contribution below 15 K.

A sensitive choline biosensor with supramolecular architecture

A sensitive biosensor with supramolecular architecture was designed and implemented here to detect choline. Choline oxidase and horseradish peroxidase were assembled onto the polymer of thiolated β-cyclodextrin and platinum nanoparticles modified gold electrode through 1-adamantane carboxylic acid coupling. Square wave voltammetry showed that the reduction currents at 0.38 mV had a linear relationship with the logarithms of choline concentrations in the range of 10 −9–10 −2 M, and the detection limit was down to 0.1 nM. Such biosensor also exhibited excellent selectivity, reproducibility and stability.

Novel ferromagnetic materials ofSmCo5 nanoparticles in single-nanometer size: chemical syntheses and characterizations

We first succeeded in preparing ferromagnetic materials ofSmCo5 nanoparticlesin sizes of single nanometers by a chemical route using a polyol process. In order to produce ferromagneticSmCo5 nanoparticleswith a CaCu5-type structure, the chemical preparation was conducted under a molar ratio of 1:1.3 ofSm:Co as compositions of metallic precursors when tetraethylene glycol (TEG), and oleicacid and oleylamine were used as a reductant and protectant, respectively. However, XRDprofiles of the products showed the presence of oxides and other by-products besides theCaCu5-type structured nanoparticles. The best metallic precursors andprotective reagent to prevent oxidization under reaction wereSmCl3 andCo(acac)3, and 1-adamantanecarboxylic acid (ACA) and poly(N-vinyl-2-pyrrolidone) (PVP), respectively when TEG was used as the reducingreagent. We found that oxides and other by-products were not detected and pureSmCo5 nanoparticleswith the CaCu5-type structure were prepared under the chemical condition. TheSmCo5 nanoparticles coated by ACA and PVP were 6.2 nm in diameter and showed a coercivity of1500 Oe at 300 K.

Quinolinotriazole-β-cyclodextrin and its adamantanecarboxylic acid complex as efficient water-soluble fluorescent Cd2+ sensors

A novel β-cyclodextrin derivative 1 bearing 8-hydroxyquinolino and triazole groups was synthesized in satisfactory yield by ‘click chemistry’. With a good water solubility up to 0.03mol/L, 1 exhibited an effective switch-on fluorescence response to Cd2+ over other common metal ions under physiological conditions. Studies on the recognition mechanism indicated that the cooperative coordination of Cd2+ with both the 8-hydroxyquinolino moiety excluded from the β-CD cavity and the triazole moiety was a crucial and basic factor to achieve the fluorescent sensing process. Significantly, spectrophotometric studies also demonstrated that, after inclusion complexation with 1-adamantanecarboxylic acid sodium salt (AdCA), the resultant 1/AdCA system gave a more effective fluorescent sensing to Cd2+ through a cyclodextrin/substrate/Cd2+ triple binding mode.

Synthesis and electrocatalytic property of cubic and spherical nanoparticles of cobalt platinum alloys

This paper describes the morphological control and electrocatalytic property of CoPt nanoparticles. Both cubic and spherical CoPt nanoparticles were made using cobalt carbonyl and platinum 2,4-pentanedionate under different reaction temperatures in the presence of capping reagents, which included adamantanecarboxylic acid and hexadecylamine. Effects of heterogeneous species on shape of the CoPt nanoparticles were examined by replacing cobalt carbonyl with silver acetylacetonate. Our results suggest that the formation of different shapes of CoPt particles could be attributed to the affinity between cobalt and platinum, and the effects of capping agents. The size and shape dependent electrocatalytic properties of these nanoparticles were examined based on the direct methanol oxidation reaction.

Supramolecular hydrogels formed by β-cyclodextrin self-association and host–guest inclusion complexes

Supramolecular hydrogels are highly interesting for drug delivery and tissue engineering applications, especially those systems that display a combination of tunable properties, high mechanical strength and easy preparation from well-available and biocompatible building blocks. In the present paper, we show that the combination of free β-cyclodextrin (βCD) and 8-arm or linear cholesterol-derivatized poly(ethylene glycol) (PEG–chol) in aqueous solution resulted in the formation of almost fully elastic gels with storage moduli in the range of 10–500 kPa. X-Ray diffraction measurements demonstrated the presence of crystalline βCD domains in the hydrogel networks. Rheological experiments further proved that hydrogel formation is based on inclusion complex formation between these βCD clusters and cholesterol coupled to the terminal end of PEG. The observation that the gels were weakened by addition of the competitive βCD–guest molecule adamantanecarboxylic acid (ACA) supported the proposed gelation mechanism. The gel mechanical properties were dependent on temperature, concentration of cholesterol-derivatized PEG and/or βCD, PEG's molecular weight and its architecture. This hydrogel system can be considered as an excellent candidate for future applications in the biomedical and pharmaceutical fields.

The first one-pot ‘alkane-like’ reactions of carbonyl-containing adamantanes

A novel ‘alkane-like’ methodology for the direct and very simple one-pot functionalization of amides and an ester of 1-adamantanecarboxylic acid provides access to new and synthetically challenging 1,3-dicarbonyl-containing adamantanoid compounds with the same or different functional groups.

Spatial Decomposition Analysis of the Thermodynamics of Cyclodextrin Complexation.

We propose a method of spatial decomposition analysis (SDA) to study the thermodynamics of association in solution, based on three-dimensional molecular theory of solvation. We decompose the solvation thermodynamics quantities into the excluded volume and solvation shell terms and further break them down into partial contributions of the functional groups of the associating species. For illustration, we applied the SDA method to the complexation of β-cyclodextrin and 1-adamantanecarboxylic acid in water. We calculated the changes in the free energy and in the partial molar volume upon the association and decomposed them into the partial contributions of the functional groups to the excluded volume and solvation shell terms. The SDA shows that the adamantyl group of 1-adamantanecarboxylic acid is responsible for the complexation more than its carboxyl group and that the carboxyl has little contribution to the association process. The SDA results are in good agreement with the observation made in a recent molecular dynamics simulation. The SDA method can reveal a microscopic picture for association processes in solution in a number of areas, including protein stability, and might be a useful tool for rational drug design.