Carboxylic Acid Compounds Research Articles

Neuroprotective effects of alpha-ketoglutarate and ethyl pyruvate against motor dysfunction and oxidative changes caused by repeated 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine exposure in mice

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin associated with drug abuse and causes permanent symptoms of Parkinson's disease (PD) by destroying dopaminergic neurons in the substantia nigra of the brain. In the present study, the neuroprotective effects of two carboxylic acid compounds, viz. alpha-ketoglutarate (A-KG), a Kreb's cycle intermediate and ethyl pyruvate (EP), a lipid-soluble analogue of pyruvate, were evaluated against MPTP intoxication in mice and compared with madopar (MD; combination of levodopa plus benserazide), a standard drug. Animals received oral treatment of A-KG (500mg/kg), EP (100mg/kg) or MD (5mg/kg) daily for 5days followed by intraperitoneal administration of MPTP (20mg/kg) and posttreatment (+10min) of A-KG, EP or MD daily for the remaining 5days. MPTP caused the inhibition of complex I of electron transport chain accompanied by oxidative stress in the brain. It also caused cytotoxicity in the midbrain region as characterized by histology and immunohistochemistry. Treatments of A-KG and EP were found to resolve the loss of motor coordination, oxidative stress, diminished complex I activity and tyrosine hydroxylase-positive neurons in midbrain. A-KG and EP also regressed the histological damage in the brain and minimized the accumulation of alpha-synuclein in the midbrain region. The data suggest that A-KG and EP which are nontoxic carboxylic acid compounds could be of potential therapeutic value in the treatment of PD.

FFA1‐selective agonistic activity based on docking simulation using FFA1 and GPR120 homology models

BACKGROUND AND PURPOSE The free fatty acid FFA1 receptor and GPR120 are GPCRs whose endogenous ligands are medium- and long-chain FFAs, and they are important in regulating insulin and GLP-1 secretion respectively. Given that the ligands of FFA1 receptor and GPR120 have similar properties, selective pharmacological tools are required to study their functions further. EXPERIMENTAL APPROACH We used a docking simulation approach using homology models for each receptor. Biological activity was assessed by phosphorylation of ERK and elevation of intracellular calcium ([Ca(2+) ]i ) in cells transfected with FFA1 receptor or GPR120. Insulin secretion from murine pancreatic beta cells (MIN6) was also measured. KEY RESULTS Calculated hydrogen bonding energies between a series of synthetic carboxylic acid compounds and the homology models of the FFA1 receptor and GPR120, using docking simulations, correlated well with the effects of the compounds on ERK phosphorylation in transfected cells (R(2) = 0.65 for FFA1 receptor and 0.76 for GPR120). NCG75, the compound with the highest predicted selectivity for FFA1 receptors from this structure-activity relationship analysis, activated ERK and increased [Ca(2+) ]i as potently as the known FFA1 receptor-selective agonist, Compound 1. Site-directed mutagenesis analysis based on the docking simulation showed that different amino acid residues were important for the recognition and activation by FFA1 receptor agonists. Moreover, NCG75 strongly induced ERK and [Ca(2+) ]i responses, and promoted insulin secretion from MIN6 cells, which express endogenous FFA1 receptors. CONCLUSION AND IMPLICATIONS A docking simulation approach using FFA1 receptor and GPR120 homology models could be useful in predicting FFA1 receptor-selective agonists.

Quantum chemical calculations of bond dissociation energies for COOH scission and electronic structure in some acids

Quantum chemical calculations are performed to investigate the equilibrium C—COOH bond distances and the bond dissociation energies (BDEs) for 15 acids. These compounds are studied by utilizing the hybrid density functional theory (DFT) (B3LYP, B3PW91, B3P86, PBE1PBE) and the complete basis set (CBS—Q) method in conjunction with the 6-311G** basis as DFT methods have been found to have low basis sets sensitivity for small and medium molecules in our previous work. Comparisons between the computational results and the experimental values reveal that CBS—Q method, which can produce reasonable BDEs for some systems in our previous work, seems unable to predict accurate BDEs here. However, the B3P86 calculated results accord very well with the experimental values, within an average absolute error of 2.3 kcal/mol. Thus, B3P86 method is suitable for computing the reliable BDEs of C—COOH bond for carboxylic acid compounds. In addition, the energy gaps between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of studied compounds are estimated, based on which the relative thermal stabilities of the studied acids are also discussed.

Assessment of community level physiological profiles and molecular diversity of soil bacteria under different cropping systems

Community level physiological profiles (CLPP) and molecular diversity of bacteria in soil under rice-rice (RR), rice-fallow (RF), rice-wheat (RW), legume (LG), mango orchard (MO), and grass land (GL) cropping systems occurring in South West Bengal, India (22°22'N latitude and 86°26'E longitude) were studied. The soils were mostly acidic (pH 5.4 to 6.85). The GL soil recorded the highest organic carbon (20.23 g kg -1 ) and total nitrogen (1.96 g kg -1 ). The RF soil was the most acidic and had the poorest nutrient contents. The CLPP, as studied by carbon source utilization in BIOLOG Ecoplates, revealed that the bacteria in soils under different cropping systems could differentially utilize all the groups of carbon sources viz. carbohydrate, amino acid, carboxylic acid, polymer, amine/amide, and phenolic compound. Carbohydrate was most utilized and amine/amide and phenolic compound were least utilized. Bacterial communities in RF soil utilized the highest amount of carbohydrate and carboxylic acid and also utilized a balanced amount of other individual carbon substrates. Molecular diversity was studied by polymerase chain reaction followed by amplified ribosomal DNA restriction analysis (ARDRA) of soil DNA. Variations in ARDRA banding pattern followed by cluster analysis and the resulting dendrogram indicated that the cropping systems induced changes in soil bacterial communities. The grouping of uncultivated soils (MO and GL) in a separate cluster clearly indicated the presence of different bacterial communities.

Line Tension and Line Activity in Mixed Monolayers Composed of Aliphatic and Terphenyl-Containing Surfactants

Custom-designed surfactants, known as "linactants", have the ability to reduce the line tension between coexisting phases within mixed monolayers of chemically dissimilar compounds at the air-water interface. Thus far, linactants have been successfully identified for only one type of chemical dissimilarity, involving mixed monolayers of hydrocarbon and fluorocarbon surfactants. In the present work, we have pursued a more general interpretation of linactant compounds by extending the concept to a new system that is comprised of a mixture of aliphatic (pentadecanoic acid) and aromatic (p-terphenyl carboxylic acid) compounds. We found that the "bare" line tension between phases of this mixed monolayer was ~4 pN, and within the same order of magnitude as our previous measurement in mixed monolayers containing hydrocarbons and fluorocarbons. Furthermore, we examined a homologous series of potential linactant compounds possessing an aliphatic tail of variable length and a p-terphenyl block. We determined that linactants with longer tails were able to reduce the line tension more efficiently and effectively. In particular, the addition of only 0.14% of a linactant with an 11-carbon chain reduced the line tension by more than a factor of 2. We hypothesize that the efficiency of this particular linactant is associated with its long tail; this creates strong van der Waals interactions with the aliphatic chains and enables the tail to adopt conformations that facilitate π-stacking interactions with the aromatic compounds within the monolayer.

Metabolism and Quantification of [18F]DPA-714, a New TSPO Positron Emission Tomography Radioligand

[(18)F]DPA-714 [N,N-diethyl-2-(2-(4-(2[(18)F]-fluoroethoxy)phenyl)5,7dimethylpyrazolo[1,5a]pyrimidin-3-yl)acetamide] is a new radioligand currently used for imaging the 18-kDa translocator protein in animal models of neuroinflammation and recently in humans. The biodistribution by positron emission tomography (PET) in baboons and the in vitro and in vivo metabolism of [(18)F]DPA-714 were investigated in rats, baboons, and humans. Whole-body PET experiments showed a high uptake of radioactivity in the kidneys, heart, liver, and gallbladder. The liver was a major route of elimination of [(18)F]DPA-714, and urine was a route of excretion for radiometabolites. In rat and baboon plasma, high-performance liquid chromatography (HPLC) metabolic profiles showed three major radiometabolites accounting for 85% and 89% of total radioactivity at 120 minutes after injection, respectively. Rat microsomal incubations and analyses by liquid chromatography-mass spectrometry (LC-MS) identified seven metabolites, characterized as O-deethyl, hydroxyl, and N-deethyl derivatives of nonradioactive DPA-714, two of them having the same retention times than those detected in rat and baboon plasma. The third plasma radiometabolite was suggested to be a carboxylic acid compound that accounted for 15% of the rat brain radioactivity. O-deethylation led to a nonradioactive compound and [(18)F]fluoroacetic acid. Human CYP3A4 and CYP2D6 were shown to be involved in the oxidation of the radioligand. Finally an easy, rapid, and accurate method--indispensable for PET quantitative clinical studies--for quantifying [(18)F]DPA-714 by solid-phase extraction was developed. In vivo, an extensive metabolism of [(18)F]DPA-714 was observed in rats and baboons, identified as [(18)F]deethyl, [(18)F]hydroxyl, and [(18)F]carboxylic acid derivatives of [(18)F]DPA-714. The main route of excretion of the unchanged radioligand in baboons was hepatobiliary while that of radiometabolites was the urinary system.

Brain-Penetrant Tetrahydronaphthalene Thromboxane A2-Prostanoid (TP) Receptor Antagonists as Prototype Therapeutics for Alzheimer’s Disease

A hallmark pathological feature of the Alzheimer's disease (AD) brain is the presence of senile plaques, which comprise amyloid β (Aβ) peptides that are derived from the amyloid precursor protein (APP). The plaque-containing AD brain is thought to be under oxidative stress, as evidenced by increased lipid oxidation products that include isoprostane-F2αIII (iPF2αIII). IPF2αIII can bind to and activate the thromboxane A2-prostanoid (TP) receptor, and TP receptor activation causes increased Aβ production through enhancement of APP mRNA stability. Moreover, TP receptor antagonists have been shown to block iPF2αIII-induced increases of Aβ secretion. Thus, the TP receptor may be a potential drug target for AD therapy. However, here we show that existing TP receptor antagonists have poor blood-brain barrier (BBB) permeability, likely due to the presence of a carboxylic acid moiety that is believed to be important for receptor interaction, but which may hamper passive diffusion across the BBB. We now report selected analogues of a known tetrahydronaphthalene TP receptor antagonist, wherein the carboxylic acid moiety has been replaced by heterocyclic bioisosteres. These heterocyclic analogues retained relatively high affinity for the mouse and human TP receptors, and, unlike the parent carboxylic acid compound, several examples freely diffused across the BBB into the brain upon administration to mice. These results reveal that brain-penetrant tetrahydronaphthalene TP receptor antagonists can be developed by substituting the carboxylic acid moiety with a suitable nonacidic bioisostere. Compounds of this type hold promise as potential lead structures to develop drug candidates for the treatment of AD.

Reactive Extraction of Cyclic Polyhydroxy Carboxylic Acid Using Trioctylamine (TOA) in Different Diluents

Quinic acid is a cyclic polyhydroxy carboxylic acid compound that is implicated in the perceived acidity of raw materials. It is a constituent of the tannins. In this work, the extraction of quinic acid was studied by using trioctylamine (TOA) with respect to the functional groups. The quinic acid extraction experiments employed TOA + solvent mixtures or pure solvent. The solvents included two acetates, two alcohols, and two ketones. The obtained experimental results of the extraction experiments are reported as distribution coefficients, KD, loading factors, Z, and extraction efficiencies, E. The highest synergistic extraction efficiency was found to be 83.191 % for the TOA + 1-octanol extractant system, which had a KD value of 4.949 and a Z value of 0.258.

Characterization of low-temperature vapour pressure estimates for secondary organic aerosol applications

Many models of secondary organic aerosol (SOA) formation, adhering to gas-particle equilibrium partitioning theory, require known vapour pressures for low volatility products of volatile organic compound (VOC) oxidation. Since the majority of such products have yet to be isolated and analysed, few experimental determinations of pertinent vapour pressures have been achieved, and models are forced to rely on vapour pressure estimates, such as those available through the common, computer-based SPARC and MPBPWIN property calculators. Thus, the accuracy of the respective estimation methods must be measured and evaluated, in order to determine the consequences in the resulting models. However, published evaluations, and most models themselves, typically focus on moderate to high ambient temperatures, which may not be applicable year-round in colder regions, where the rate of VOC oxidation slows, while the vapour pressures of the products decrease, indicating an increased tendency to condense into the aerosol phase. In this paper, the accuracy of the SPARC and MPBPWIN methods is evaluated over a broad temperature range, from 248.15 to 298.15K, in five degree intervals using a test set of 45 compounds. The results are reported in terms of mean average error (MAE) and mean bias error (MBE), and given for alcohol, carboxylic acid, aldehyde, and ketone compound classes at each temperature. Specific trends in MAE and MBE with regard to compound class and changing temperature are discussed. More generally, the evaluation indicates that SPARC, with MAE decreasing from 0.288 at 248.15K to 0.165 at 298.15K and MBE increasing from −0.180 at 248.15K to a peak of −0.081 at 293.15K, is more accurate at low to moderate temperatures than MPBPWIN, with MAE decreasing from 0.436 at 248.15K to 0.272 at 298.15K and MBE increasing from −0.328 at 248.15K to −0.213 at 298.15K. Decreasing accuracy at lower temperatures emphasizes a need for focused experimental and model efforts in this temperature range.

Development of Potentiometric Lead Ion Sensors Based on Ionophores Bearing Oxygen/Sulfur Functional Groups

Potentiometric Pb(Ⅱ) sensors based on oxygen/sulfur functional groups-bearing ionophores,including anthraquinone,aromatic carboxylic acid,carboxylate,phosphate and macrocyclic compounds containing amide or thioamide groups,are systematically summarized.Anthraquinone is found to be quickly responsive ionophores to lead ions with the shortest response time of down to 2 s.Aromatic carboxylic acid with sulfur atom as an ionophore in an asymmetric membrane sensitively responds to lead ions with detection limit of 6.0×10-10 mol/L.Phosphate has advantage of better anti-interference ability with the selective coefficient logK of smaller than 3.0.The macrocyclic amide compound as ionophore has been assembled into microelectrode for sensing confined sample in a 3-μL measuring cell with a superior lower detection limit of 2.7×10-9 mol/L.

Synthesis and contractile activity of substituted 1,2,3,4-tetrahydroisoquinolines.

A series of different 1-monosubstituted and 1,1-disubstituted 1,2,3,4-tetrahydro-isoquinolines was synthesized in high yields from different ketoamides. We have developed a convenient method for the synthesis of disubstituted derivatives by interaction of ketoamides with organomagnesium compounds, followed by cyclization in the presence of catalytic amounts of p-toluenesulfonic acid (PTSA). A number of substituents at the C-1 in the isoquinoline skeleton were introduced varying either carboxylic acid or organomagnesium compound. Some of the obtained 1,1-dialkyl-1,2,3,4-tetrahydro-isoquinolines possess contractile activity against guinea pig’s gastric smooth muscle preparations.

Synthesis and performance of novel hydroxycarbamoyl carboxylic acids for the flotation of diaspore and aluminosilicate minerals

Novel compounds of hydroxycarbamoyl carboxylic acids, including 2-hydroxycarbamoyl-3-methlcyclohexane carboxylic acid (HCMC), 2-hydroxycarbamoylmethyl decylen-4-yl carboxylic acid (HCDC) and 2-hydroxycarbamoylmethyl tridecylen-4-yl carboxylic acid (HCTC) were synthesized. The flotation behaviors of diaspore, kaolinite and illite using these compounds as collectors were investigated. The flotation results revealed that the floatability of the minerals was, in descending order, diaspore and kaolinite, followed by illite, and the ability to collect the minerals was, in ascending order, HCMC and HCDC, followed by HCTC. At a dosage of 2×10−4 mol/L, both HCDC and HCTC show a strong ability to collect diaspore and a weak ability to float kaolinite and illite. The flotation recovery of diaspore is over 90% and that of kaolinite and illite less than 30%. Moreover, Fourier transform infrared spectroscopy (FTIR) spectrum and zeta potential, as well as the adsorption amount, indicated that the adsorption interaction between HCTC and diaspore was primarily a kind of chemisorption in the form of chelate rings, while the interaction between the collector and aluminosilicate mineral was dominated by physisorption. It was concluded that the novel hydroxycarbamoyl carboxylic acid compounds are highly selective collectors for the flotation of diaspore vs. aluminosilicate minerals

Effect of C-Terminal Modification on the Self-Assembly and Hydrogelation of Fluorinated Fmoc-Phe Derivatives

The development of hydrogels resulting from the self-assembly of low molecular weight (LMW) hydrogelators is a rapidly expanding area of study. Fluorenylmethoxycarbonyl (Fmoc) protected aromatic amino acids derived from phenylalanine (Phe) have been shown to be highly effective LMW hydrogelators. It has been found that side chain functionalization of Fmoc-Phe exerts a significant effect on the self-assembly and hydrogelation behavior of these molecules; fluorinated derivatives, including pentafluorophenylalanine (F(5)-Phe) and 3-F-phenylalanine (3-F-Phe), spontaneously self-assemble into fibrils that form a hydrogel network upon dissolution into water. In this study, Fmoc-F(5)-Phe-OH and Fmoc-3-F-Phe-OH were used to characterize the role of the C-terminal carboxylic acid on the self-assembly and hydrogelation of these derivatives. The C-terminal carboxylic acid moieties of Fmoc-F(5)-Phe-OH and Fmoc-3-F-Phe-OH were converted to C-terminal amide and methyl ester groups in order to perturb the hydrophobicity and hydrogen bond capacity of the C-terminus. Self-assembly and hydrogelation of these derivatives was investigated in comparison to the parent carboxylic acid compounds at neutral and acidic pH. It was found that hydrogelation of the C-terminal acids was highly sensitive to solvent pH, which influences the charge state of the terminal group. Rigid hydrogels form at pH 3.5, but at pH 7 hydrogel rigidity is dramatically weakened. C-terminal esters self-assembled into fibrils only slowly and failed to form hydrogels due to the higher hydrophobicity of these derivatives. C-terminal amide derivatives assembled much more rapidly than the parent carboxylic acids at both acidic and neutral pH, but the resultant hydrogels were unstable to shear stress as a function of the lower water solubility of the amide functionality. Co-assembly of acid and amide functionalized monomers was also explored in order to characterize the properties of hybrid hydrogels; these gels were rigid in unbuffered water but significantly weaker in phosphate buffered saline. These results highlight the complex nature of monomer/solvent interactions and their ultimate influence on self-assembly and hydrogelation, and provide insight that will facilitate the development of optimal amino acid LMW hydrogelators for gelation of complex buffered media.

A novel method for bromodecarboxylation of α,β-unsaturated carboxylic acids using catalytic sodium nitrite

A first novel synthetic utility of catalytic sodium nitrite in combination with aqueous HBr, for bromo decarboxylation of α,β-unsaturated carboxylic acid is described. α,β-Unsaturated carboxylic acid compounds successfully converted into corresponding bromo compounds. The advantages of this protocol are shorter reaction time and moderate to good yields.

Changes in the compound classes of dissolved organic matter along an estuarine transect: A study using FTIR and 13C NMR

In this work, we use Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy ( 13C NMR) data to quantify the changes of major chemical compound classes (carboxylic acid, amide, ester, aliphatic, aromatic and carbohydrate) in high molecular weight (HMW, >1 kDa) dissolved organic matter (DOM) isolated along a transect through the Elizabeth River/Chesapeake Bay system to the coastal Atlantic Ocean off Virginia, USA. Results show that carboxylic acids and aromatic compounds are lost along the transect, while HMW DOC becomes enriched in carbohydrate moieties that could have a mid-transect source, perhaps the intensive red tide bloom ( Choclodinium polykrikoides) which occurred during our sampling period. Taking the second derivative of the FTIR spectra resolved three pools of de-protonated carboxylic acids at our Dismal Swamp site (used to represent terrestrial organic matter in this area): one carboxylic acid pool, complexed with iron, seems to be lost between the Dismal Swamp and river sites; the second appears biogeochemically active throughout the riverine transect, disappearing in the coastal ocean sample; the third seems refractory, with the potential to be transported to and to accumulate within the open ocean. Five-member ring esters (γ-lactones) were the major ester form in the Dismal Swamp; aliphatic and acetate esters were the dominant esters in the estuary/marine DOM. No amide groups were detectable in Dismal Swamp DOM; secondary amides were present at the estuarine/marine sites. Coupling FTIR with 13C NMR provides new insights into the biogeochemical roles of carboxylic acid, amide and ester compounds in aquatic ecosystems.

Optimization of process for the production of bio-oil from eucalyptus wood

The pyrolysis of eucalyptus wood was carried out in a batch reactor to optimize the yield of bio-oil. Effect of various parameters such as feed (particle) size, temperature, presence of catalyst, and heating rate on the yield of bio-oil was investigated. The optimum conditions for the high yield of bio-oil are with fast heating rate, pyrolysis temperature of 450°C, and using the particle size of 2–5 mm (average l/ d=12.84/2.03 mm). The reaction kinetics and the quality of bio-oil produced are independent of the presence of different catalysts such as mordenite, kaoline clay, fly ash, and silica–alumina. The physical properties such as odor, color, pH, viscosity, and heating value were determined. The FTIR analysis of bio-oil indicates the presence of different functional groups such as monomeric alcohol, phenol, ketones, aldehydes, carboxylic acid, amines, and nitro compounds. The composition of the bio-oil at different conditions was analyzed using GC-MS and found that the components are temperature-dependent but independent of catalysts used.

1,3,7-Trimethyl-2,4-dioxo-1,2,3,4-tetrahydropteridine-6-carboxylic acid hemihydrate

In the title compound, C10H10N4O4·0.5H2O, the two rings of the pteridine system are nearly coplanar [dihedral angle = 4.25 (9)°]. The atoms of the carboxyl group are also coplanar with the pteridine unit [r.m.s. deviation from the mean plane of the pteridine skeleton = 0.092 (2) Å]. In the crystal, the presence of the water molecule of crystallization (O atom site symmetry 2) leads to a hydrogen-bonding pattern different from the one shown by many carboxylic acid compounds (dimers formed through O—H⋯O hydrogen bonds between neighbouring carboxyl groups): in the present structure, the water mol­ecule, which lies on a binary axis, acts as a bridge between two mol­ecules, forming a hydrogen-bonded dimer. In addition to the hydrogen bonds, there are π–π ring stacking inter­actions involving the pyrimidine and pyrazine rings [centroid–centroid distance = 3.689 (1)Å], and two different pyrazine rings [centroid–centroid distance = 3.470 (1)Å]. Finally, there is a C—O⋯π contact involving a carboxyl­ate C—O and the pyrimidine ring with a short O⋯Cg distance of 2.738 (2) Å.

Sulfonic acid resin-catalyzed addition of phenols, carboxylic acids, and water to olefins: Model reactions for catalytic upgrading of bio-oil

Acid-catalyzed 1-octene reactions with phenol and mixtures of phenol with water, acetic acid and 1-butanol were studied as partial bio-oil upgrading models. Bio-oil from fast biomass pyrolysis has poor fuel properties due to the presence of substantial amounts of water, carboxylic acid, phenolic derivatives and other hydroxyl-containing compounds. Additions across olefins offer a route to simultaneously lower water content and acidity while increasing hydrophobicity, stability and heating value. Amberlyst15, Dowex50WX2 and Dowex50WX4 effectively catalyzed phenol O- and C-alkylation from 65 to 120 °C, giving high O-alkylation selectivities in the presence of water, acetic acid and 1-butanol. Octanols and dioctyl ethers were formed from water and octyl acetates and phenol acetates from acetic acid. Phenol alkylation slowed in the presence of water. Dowex50WX2 and Dowex50WX4 were more stable in the presence of water than Amberlyst15 and were successfully recycled. Adding 1-butanol to phenol/water/1-octene, gave emulsion-like mixtures which improved phenol conversion and olefin hydration.

Electrospray ionization mass spectrometry studies of cyclodextrin‐carboxylate ion inclusion complexes

Aqueous solutions containing simple model aliphatic and alicyclic carboxylic acids (surrogates 1-4) were studied using negative ion electrospray mass spectrometry (ESI-MS) in the presence and absence of alpha-, beta-, and gamma-cyclodextrin. Molecular ions were detected corresponding to the parent carboxylic acids and complexed forms of the carboxylic acids; the latter corresponding to non-covalent inclusion complexes formed between carboxylic acid and cyclodextrin compounds (e.g., beta-CD, alpha-CD, and gamma-CD). The formation of 1:1 non-covalent inclusion cyclodextrin-carboxylic complexes and non-inclusion forms of the cellobiose-carboxylic acid compounds was also observed.Aqueous solutions of Syncrude-derived mixtures of aliphatic and alicyclic carboxylic acids (i.e. naphthenic acids; NAs) were similarly studied using ESI-MS, as outlined above. Molecular ions corresponding to the formation of CD-NAs inclusion complexes were observed whereas 1:1 non-inclusion forms of the cellobiose-NAs complexes were not detected. The ESI-MS results provide evidence for some measure of inclusion selectivity according to the 'size-fit' of the host and guest molecules (according to carbon number) and the hydrogen deficiency (z-series) of the naphthenic acid compounds. The relative abundances of the molecular ions of the CD-carboxylate anion adducts provide strong support for differing complex stability in aqueous solution. In general, the 1:1 complex stability according to hydrogen deficiency (z-series) of naphthenic acids may be attributed to the nature of the cavity size of the cyclodextrin host compounds and the relative lipophilicity of the guest.

Novel 1-hydroxy-1,1-bisphosphonates derived from indazole: synthesis and characterization

Bisphosphonates (BPs) are an important class of drugs used in the treatment of abnormal calcium metabolism diseases. The first syntheses of bisphosphonates derived from indazole, substituted at the N-1, N-2 and C-3 positions are reported. The 1-hydroxy-1,1-bisphosphonates were synthesized from the corresponding carboxylic acid or acyl chloride compounds, by two different methods. These BPs have a side chain with different lengths ((CH2)n, n = 0-5) between the indazole ring and the bisphosphonate group.