ABSTRACT
While cancer is the leading cause of human's deaths worldwide, finding an imaging agent which can detect cancer tumours is needed for cancer diagnosis. In the present study, PEG-citrate dendrimer-G2 was used as a nano-carrier of FITC dye and Iohexol to help passive targeting and uptake of both imaging agents in cancer cells/tumour in vitro and in vivo. Dendrimer was synthesisedand the product characterised using LC-MS, FT-IR, DLS, ELS, AFM, and 1HNMR. After FITC loading into dendrimer, MTT was performed to determine the cytotoxicity of formulation on HEK-293 and MCF-7 cells. In vitro imaging using dendrimer-FITC was done via fluorescent microscope thereafter. Moreover, CT imaging using Iohexol was employed to show the targeting nature and ability of the complex to use as imaging agent in vivo. Data yielded in this study corroborate the notion that the promised dendrimer was synthesised properly and had no toxicity along with FITC on normal cell. Furthermore, CT and fluorescent images showed the targeting nature and imaging ability of Iohexol/FITC loaded dendrimer in vitro and in vivo. Overall, results showed promising characteristics of the novel complexes using dendrimer-G2 both in vitro and in vivo.
Subject(s)
Citric Acid/chemistry , Dendrimers/chemistry , Diagnostic Imaging/methods , Fluorescent Dyes/chemistry , Polyethylene Glycols/chemistry , Citrates/chemical synthesis , Citrates/chemistry , Dendrimers/chemical synthesis , Drug Carriers , Fluorescein-5-isothiocyanate/chemistry , Fluorescent Dyes/chemical synthesis , HEK293 Cells , Humans , MCF-7 Cells , Staining and Labeling/methodsABSTRACT
Siderophores are small molecules used to specifically transport iron into bacteria via related receptors. By adapting siderophores and hijacking their pathways, we may discover an efficient and selective way to target microbes. Herein, we report the synthesis of a siderophore-fluorophore conjugate VF-FL derived from vibrioferrin (VF). Using flow cytometry and fluorescence microscopy, the probe selectively labeled vibrios, including V. parahaemolyticus, V. cholerae, and V. vulnificus, even in the presence of other species such as S. aureus and E. coli. The labeling is siderophore-related and both iron-limited conditions and the siderophore moiety are required. The competitive relationship between VF-FL and VF in vibrios implies an unreported VF-related transport mechanism in V. cholerae and V. vulnificus. These studies demonstrate that the siderophore scaffold provides a method to selectively target microbes expressing cognate receptors under iron-limited conditions.
Subject(s)
Citrates/metabolism , Fluorescent Dyes/metabolism , Pyrrolidinones/metabolism , Siderophores/metabolism , Vibrio/isolation & purification , Vibrio/metabolism , Biological Transport , Citrates/chemical synthesis , Citrates/chemistry , Escherichia coli/metabolism , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/chemistry , Humans , Microscopy, Fluorescence/methods , Pyrrolidinones/chemical synthesis , Pyrrolidinones/chemistry , Siderophores/chemical synthesis , Siderophores/chemistry , Staphylococcus aureus/metabolism , Vibrio Infections/microbiologyABSTRACT
The viridiofungin analogue NA808 was synthesized by the stereoselective Ireland-Claisen rearrangement of dienylmethyl ester, regioselective bromolactonization of ß-divinylpropanoic acid and retro-bromolactonization.
Subject(s)
Antiviral Agents/chemical synthesis , Carboxylic Acids/chemistry , Citrates/chemistry , Citrates/chemical synthesis , Furans/chemistry , Tyrosine/analogs & derivatives , Antiviral Agents/chemistry , Carboxylic Acids/chemical synthesis , Furans/chemical synthesis , Halogenation , Lactones/chemical synthesis , Lactones/chemistry , Stereoisomerism , Tyrosine/chemical synthesis , Tyrosine/chemistryABSTRACT
INTRODUCTION: Gallium-68 citrate has been successfully applied in the PET imaging of infections and inflammation in some centers; however further evaluation of the tracer in inflammation models is of great importance. METHODS: 68Ga-citrate prepared from [68Ga]GaCl3 (eluted form an SnO2 based 68Ge/68Ga generator) and sodium citrate at optimized conditions followed by quality control tests was injected to normal and turpentine-oil induced rats PET/CT imaging studies up to 290 min. RESULTS: 68Ga-citrate was prepared with acceptable radiochemical purity (>99 ITLC, >99% HPLC), specific activity (28-30 GBq/mM), chemical purity (Sn, Fe <0.3 ppm; Zn<0.2 ppm) in 15 min at 50°C. PET/CT imaging of the tracer demonstrated early detection of inflamed site in animal models in 60-80 min. CONCLUSION: This study demonstrated possible early detection of inflammation foci in vivo using 68Ga-citrate prepared using commercially available 68Ge/68Ga generators for PET imaging.
Subject(s)
Citrates/chemical synthesis , Gallium Radioisotopes/chemistry , Germanium/chemistry , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals/chemical synthesis , Tin Compounds/chemistry , Animals , Chromatography, High Pressure Liquid , Rats , Rats, Sprague-Dawley , TurpentineABSTRACT
Marine mussels tightly adhering to various underwater surfaces inspires human to design adhesives for wet tissue adhesion in surgeries. Characterization of mussel adhesive plaques describes a matrix of proteins containing 3,4-dihydroxyphenylalanine (DOPA), which provides strong adhesion in aquatic conditions. Several synthetic polymer systems have been developed based on this DOPA chemistry. Herein, a citrate-based tissue adhesives (POEC-d) was prepared by a facile one-pot melt polycondensation of two diols including 1,8-octanediol and poly(ethylene oxide) (PEO), citric acid (CA) and dopamine, and the effects of hydrophilic and soft PEO on the properties of adhesives were studied. It was found that the obtained adhesives exhibited water-soluble when the mole ratio of PEO to 1,8-octanediol was 70%, and the equilibrium swelling percentage of cured adhesive was about 144%, and degradation rate was in the range of 1-2 weeks. The cured adhesives demonstrated soft rubber-like behavior. The lap shear adhesion strength measured by bonding wet pig skin was in the range of 21.7-33.7 kPa, which was higher than that of commercial fibrin glue (9-15 kPa). The cytotoxicity tests showed the POEC-d adhesives had a low cytotoxicity. Our results supports that POEC-d adhesives, which combined strong wet adhesion with good biodegradability, acceptable swelling ratio, good elasticity and low cytotoxicity, have potentials in surgeries where surgical tissue adhesives, sealants, and hemostatic agents are used.
Subject(s)
Biomimetic Materials , Bivalvia/chemistry , Catechols/chemistry , Citric Acid/chemistry , Polyethylene Glycols/chemistry , Tissue Adhesives , Animals , Biomimetic Materials/chemical synthesis , Biomimetic Materials/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Citrates/chemical synthesis , Citrates/chemistry , Citrates/pharmacology , Keratinocytes/cytology , Keratinocytes/drug effects , Keratinocytes/physiology , Materials Testing , Polymers/chemical synthesis , Polymers/chemistry , Polymers/pharmacology , Shear Strength/drug effects , Skin/cytology , Skin/drug effects , Swine , Tissue Adhesives/chemical synthesis , Tissue Adhesives/chemistry , Tissue Adhesives/pharmacologyABSTRACT
Staphyloferrin B (SB) is a citrate-based polycarboxylate siderophore produced and utilized by the human pathogen Staphylococcus aureus for acquiring iron when colonizing the vertebrate host. The first chemical synthesis of SB is reported, which enables further molecular and biological characterization and provides access to structural analogues of the siderophore. Under conditions of iron limitation, addition of synthetic SB to bacterial growth medium recovered the growth of the antibiotic resistant community isolate S. aureus USA300 JE2. Two structural analogues of SB, epiSB and SBimide, were also synthesized and employed to investigate how epimerization of the citric acid moiety or imide formation influence its function as a siderophore. Epimerization of the citric acid stereocenter perturbed the iron-binding properties and siderophore function of SB as evidenced by experimental and computational modeling studies. Although epiSB provided growth recovery to S. aureus USA300 JE2 cultured in iron-deficient medium, the effect was attenuated relative to that of SB. Moreover, SB more effectively sequestered the Fe(III) bound to human holo-transferrin, an iron source of S. aureus, than epiSB. SBimide is an imide analogous to the imide forms of other citric acid siderophores that are often observed when these molecules are isolated from natural sources. Here, SBimide is shown to be unstable, converting to native SB at physiological pH. SB is considered to be a virulence factor of S. aureus, a pathogen that poses a particular threat to public health because of the number of drug-resistant strains emerging in hospital and community settings. Iron acquisition by S. aureus is important for its ability to colonize the human host and cause disease, and new chemical insights into the structure and function of SB will inform the search for new therapeutic strategies for combating S. aureus infections.
Subject(s)
Citrates/chemical synthesis , Citrates/metabolism , Siderophores/chemical synthesis , Siderophores/metabolism , Staphylococcus aureus/metabolism , Citrates/chemistry , Humans , Iron/metabolism , Models, Molecular , Siderophores/chemistry , Staphylococcal Infections/microbiology , Staphylococcus aureus/chemistry , Staphylococcus aureus/growth & development , StereoisomerismABSTRACT
Centhaquin is a compound that produces hypotension and bradycardia in higher doses and resuscitation in lower doses. It is water insoluble, and is unsuitable for intravenous use. We prepared the citrate salt of centhaquin and evaluated its cardiovascular efficacy vs. centhaquin. Centhaquin citrate was prepared and characterized; its purity was determined by HPLC. Mean arterial pressure (MAP), heart rate (HR), pulse pressure (PP), cardiac output (CO), stroke volume (SV) and stroke work (SW) following intravenous administration of centhaquin and the citrate (0.05, 0.15 and 0.45 mg.kg(-1)) were determined in anaesthetized male Sprague-Dawley rats. Centhaquin citrate was 99.8% pure and water soluble. Centhaquin (0.05, 0.15 and 0.45 mg.kg(-1)) produced a maximal decrease in MAP of 15.6, 25.2 and 28.1%, respectively; while centhaquin citrate produced a greater (p<0.001) decrease of 35.7, 47.1 and 54.3%, respectively. The decrease in PP and HR produced by the citrate was greater than centhaquin (p<0.001). At 0.45 mg.kg(-1) centhaquin produced a maximal decrease of 20.9% (p<0.01) in CO, while centhaquin citrate produced a decrease of 42.1% (p<0.001). Reduction in SV (p<0.01) and SW (p<0.001) produced by centhaquin citrate were greater than centhaquin. Centhaquin citrate has greater cardiovascular activity compared to centhaquin.
Subject(s)
Citrates/pharmacology , Hemodynamics/drug effects , Piperazines/pharmacology , Animals , Citrates/chemical synthesis , Dose-Response Relationship, Drug , Male , Piperazines/chemical synthesis , RatsABSTRACT
In this paper, citric acid, 1,8-octanediol and 1,2-propanediol were used as reactive monomers to synthesize poly(1,2-propanediol-co-1,8-octanediol-co-citrate) (PPOC) elastomers by melt polycondensation. The PPOC elastomers were characterized by FTIR, 1H-NMR, thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), hydrophilic test and mechanical test. The results indicated that citric acid had reacted with 1,8-octanediol and 1,2-propanediol, respectively. The sol content, swelling degree and hydrophilicity of PPOC elastomers increased with the higher content of 1,2-propanediol, while the tensile strength and the thermal degradation temperature decreased. The results indicate the addition of 1,2-propanediol reduces the crosslinking density and the flexibility of PPOC elastomers.
Subject(s)
Biocompatible Materials/chemistry , Citrates/chemistry , Citric Acid/chemistry , Octanols/chemistry , Polymers/chemistry , Propylene Glycol/chemistry , Tissue Engineering/instrumentation , Biocompatible Materials/chemical synthesis , Calorimetry, Differential Scanning , Citrates/chemical synthesis , Cross-Linking Reagents/chemistry , Elasticity , Elastomers , Hydrophobic and Hydrophilic Interactions , Magnetic Resonance Spectroscopy , Materials Testing , Polymers/chemical synthesis , Spectroscopy, Fourier Transform Infrared , Temperature , Tensile Strength , ThermogravimetryABSTRACT
Our aim was to develop a practical method to prepare 68Ga-citrate using a SnO2-based 68Ge/68Ga generator and evaluate its use in infection imaging. 68Ga-citrate synthesis was performed in a straight forward, quantitative, one-step-aseptic procedure; an amended labeling method was applied using ACD-A buffered citrate as a precursor. Study participants were imaged on a Siemens Biograph 40 PET/CT scanner 60 min post intravenous injection. Our results showed: 90%-95% 68Ga-yield was obtained and subsequently used at 324-527 MBq to perform three to four parallel 68Ga-citrate syntheses. 68Ga-citrate of 96%-99% was yielded after 10 min incubation. The radiochemical purity was >99% with a pH value of 4.0-4.5. All other quality control requirements were met. The 68Ga-citrate stability was >96%. The final product was sterile, pyrogen and solvent-free, with very low 68Ge-levels, with 191±33 MBq in 6.6±2.8 mL. High quality images were obtained at 60 min post injection of 185 MBq of 68Ga-citrate. In conclusion, a fast, direct and cheap method with a quantitative preparation of 68Ga-citrate was described. We reported on the adaptations needed when using a SnO2-based 68Ge/68Ga generator and ACD-A buffered citrate as a precursor. This method allowed for multiple patient productions from one generator elution, with 300 MBq/patient of 68Ga-citrate produced in less than 30 min and excellent labeling reproducibility for routine infection imaging.
Subject(s)
Citrates/chemical synthesis , Gallium , Germanium/chemistry , Infections/diagnostic imaging , Inflammation/diagnostic imaging , Neoplasms/diagnostic imaging , Tin Compounds/chemistry , Humans , Isotope Labeling/methods , Radioisotopes/chemistry , Radionuclide Imaging , Radiopharmaceuticals/chemical synthesis , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
OBJECTIVES: 67Ga-Citrate has been extensively used for infection and inflammation imaging for the past four decades but has limitations. In the present study, we explored the ability of 68Ga-Citrate to detect Staphylococcus aureus (Staph A) infection in rats and further studied its ability to localize intra-abdominal infection in a patient. METHODS: An infection was induced in male Wistar rats by injecting Staph A in the right thigh muscle. In this study a simple method was described for the preparation of 68Ga-Citrate with > 99% yield and purity. 68Ga-Citrate (15 MBq/rat and 150 MBq/patient) was injected intravenously and the images were acquired for 10 min each. RESULTS: 68Ga-Citrate uptake was moderate at the infection lesion within 5 min post injection but intense focal uptake was visualized from 30 min to 6 hr post-injection in rats. Cardiac blood pool and liver activity decreased during the same period of study. In the patient studied, an infected area in the abdomen at the site of recent appendectomy was detected within 30min post-injection of 68Ga-Citrate, which was consistent with CT and microbiology findings. CONCLUSION: A simple method of preparation of 68Ga-Citrate with > 99% yield and purity was described, suitable for routine clinical work. Our results showed 68Ga-Citrate is capable of detecting Staph A infection in rats and an intraabdominal infection in a post-operative patient. These findings indicate the high potential of 68Ga-Citrate for clinical utility.
Subject(s)
Appendectomy , Citrates , Gallium , Intraabdominal Infections/diagnostic imaging , Postoperative Complications/diagnostic imaging , Radiopharmaceuticals , Staphylococcal Infections/diagnostic imaging , Animals , Citrates/chemical synthesis , Citrates/pharmacokinetics , Gallium/pharmacokinetics , Humans , Male , Positron-Emission Tomography , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Rats , Rats, Wistar , Staphylococcus aureusABSTRACT
A stereoselective synthesis of (-)-viridiofungin A is described. The convergent synthesis utilized a unique highly diastereoselective multicomponent reaction between optically active phenyldihydrofuran and an α-ketoester to provide two chiral centers including a quarternary carbon center in a single step. Other key steps include an acyloxycarbonium ion-mediated tetrahydrofuran ring-opening reaction and a Julia-Kocienski olefination.
Subject(s)
Citrates/chemical synthesis , Titanium/chemistry , Tyrosine/analogs & derivatives , Molecular Structure , Stereoisomerism , Tyrosine/chemical synthesisABSTRACT
Poly(octanediol-co-citrate) elastomers containing high loading of lidocaine were synthesized at temperatures below 100 °C by means of using deep eutectic mixtures of 1,8-octanediol and lidocaine. The preservation of lidocaine integrity resulted in high-capacity drug-eluting elastomers.
Subject(s)
Anesthetics, Local/administration & dosage , Citrates/chemistry , Drug Carriers/chemistry , Elastomers/chemistry , Lidocaine/administration & dosage , Polymers/chemistry , Chemistry Techniques, Synthetic , Citrates/chemical synthesis , Drug Carriers/chemical synthesis , Elastomers/chemical synthesis , Hot Temperature , Polymers/chemical synthesis , Solvents/chemistryABSTRACT
The chromium citrate complex [CrCIT] was synthesized and its structure was determined by infrared, UV-visible and atomic absorption spectroscopy, elemental and thermodynamic analysis. Anti-diabetic activity, oxidative DNA damage capacity and acute oral toxicity of [CrCIT] were investigated and compared with that of chromium trichloride hexahydrate. [CrCIT] was synthesized in a single step reaction by chelating chromium(III) with citric acid in aqueous solution. The molecular formula of [CrCIT] was inferred as CrC(6)H(5)O(7)·4H(2)O. The anti-diabetic activity of the complex [CrCIT] was assessed in alloxan-diabetic rats by daily oral gavage for 3 weeks. The biological activity results showed that the complex at the dose of 0.25-0.75 mg Cr/kg body weight could decrease the blood glucose level and increase liver glycogen level in alloxan-diabetic rats. [CrCIT] had more beneficial influences on the improvement of controlling blood glucose, serum lipid and liver glycogen levels compared with CrCl(3)·6H(2)O. Furthermore, [CrCIT] did not cause oxidative DNA damage under physiologically relevant conditions, and [CrCIT] did not produce any hazardous symptoms or deaths in acute oral toxicity test, showing the LD(50) value for female and male rats were higher than 15.1 g/kg body weight. The results suggested that [CrCIT] might represent a novel and proper chromium supplement with potential therapeutic value to control blood glucose in diabetes.
Subject(s)
Chromium/therapeutic use , Citrates/therapeutic use , Coordination Complexes/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Animals , Blood Glucose/metabolism , Body Weight , Cholesterol/blood , Chromium/chemistry , Chromium/toxicity , Citrates/chemical synthesis , Citrates/chemistry , Citrates/toxicity , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Coordination Complexes/toxicity , DNA Damage , Diabetes Mellitus, Experimental/blood , Female , Glycogen/metabolism , Hypoglycemic Agents , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Oxidative Stress , Rats , Toxicity Tests , Triglycerides/bloodABSTRACT
We have developed novel poly(diol citrate) elastomers, which are capable of providing localized and sustained release of nitric oxide (NO). The elastomer prepolymer was obtained by condensation of citric acid, 1,8-octanediol, and N,N'-bis(2-hydroxyethyl)ethylenediamine at 130 degrees C for 40 min. Films were prepared by solvent casting followed by crosslinking at 80 degrees C for 4 days. Mechanical properties were tested. NO-releasing expanded poly(tetrafluoroethylene) (ePTFE) vascular grafts were fabricated by coating the graft's lumen with the prepolymer and crosslinking it at 80 degrees C for 4 days prior to diazeniumdiolation. Samples were diazeniumdiolated via exposure to pressurized NO. Cell compatibility was assessed by monitoring the proliferation of porcine aortic smooth muscle cells (PASMC) on the elastomers. Degradation in phosphate buffer saline (PBS) (pH = 7) at 37 degrees C was evaluated for up to 6 weeks. The secondary amine-containing poly(diol citrate) films had a Young's modulus that ranged from 5.91 to 32.64 MPa, an ultimate tensile stress that ranged from 1.47 to 10.71 MPa, and an elongation at break from 200 to 260%, depending on the content of secondary amine in the feed monomer. These elastomers were degradable and compatible with PASMC. Furthermore, degradation rate was found to be independent of the content of secondary amines in the prepolymer. The NO release from diazeniumdiolated films and ePTFE grafts was sustained for two days. In conclusion, these novel diazeniumdiolated polyester elastomers may be useful in medical devices that require blood contact or control of cell proliferation.
Subject(s)
Biocompatible Materials/chemical synthesis , Citrates/chemical synthesis , Elastomers/chemical synthesis , Nitric Oxide/metabolism , Polymers/chemical synthesis , Animals , Azo Compounds/chemistry , Biocompatible Materials/chemistry , Citrates/chemistry , Elastomers/chemistry , Mechanical Phenomena/drug effects , Microscopy, Electron, Scanning , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , Polymers/chemistry , Polytetrafluoroethylene/pharmacology , Spectroscopy, Fourier Transform Infrared , Sus scrofa , TemperatureABSTRACT
Aminocitrate (and homolog) derivatives have been prepared by bis-alkylation of glycinate Schiff bases with bromoacetates (and ethyl acrylate), followed by N-acylation and esters (partial or complete) deprotection. Aminoisocitrate was similarly obtained by mono-alkylation with diethyl fumarate. Evaluation against representative beta-lactamases revealed that the free acid derivatives are modest inhibitors of class A enzymes, whilst their benzyl esters showed a good inhibition of OXA-10 (class D enzyme). A docking experiment featured hydrophobic interactions in the active site.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Citrates/chemistry , Enzyme Inhibitors/chemical synthesis , Isocitrates/chemistry , beta-Lactamase Inhibitors , Acylation , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Catalytic Domain , Citrates/chemical synthesis , Computer Simulation , Crystallography, X-Ray , Drug Discovery , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Isocitrates/chemical synthesis , beta-Lactamases/metabolismABSTRACT
INTRODUCTION AND AIM: Scintigraphic imaging of infection and inflammation with 67Ga-citrate is an established and powerful diagnostic tool in the management of patients with infectious or inflammatory diseases. 68Ga is a short-lived positron-emitting radionuclide (half-life 67.6 min, positron energy 2.92 MeV), which allows better imaging qualities than 67Ga using the high spatial resolution and the quantitative features of PET. The aim of this study was to develop a method of synthesis for 68Ga citrate with high and reproducible radiochemical yield using a commercial 68Ga-labelling module. The resultant 68Ga citrate would be suitable for use in the detection of infectious or inflammatory diseases in routine clinical practice. METHODS: A simplified method of producing 68Ga citrate is described. Radiochemical purity, pyrogen testing were performed as per the standard protocols. RESULTS: After performing 10 syntheses of 68Ga citrate, the radiochemical yield was 64.1+/-6.0% (mean+/-standard deviation) with an average activity of 971.2+/-103.4 MBq available for labelling. Radiochemical purity determined by instant thin-layer chromatography-silica gel was higher than 98%. All the synthesized products were found to be sterile and pyrogen-free. In this study, the quality control step provided good and reproducible results. This is worth noting, especially in view of the stringent new rules adopted in most European countries for the in-house good manufacturing practice (GMP) synthesis of radiopharmaceuticals. CONCLUSION: The high radiochemical yield and purity showed that this method is a reliable tool for the production of 68Ga citrate to be used in the detection of inflammatory and infectious diseases using high resolution and qualitative PET.
Subject(s)
Citrates/chemical synthesis , Gallium , Citrates/chemistry , Citrates/standards , Communicable Diseases/diagnostic imaging , Gallium/chemistry , Gallium/standards , Gallium Radioisotopes/chemistry , Humans , Hydrogen-Ion Concentration , Inflammation/diagnostic imaging , Octreotide/analogs & derivatives , Octreotide/chemistry , Positron-Emission Tomography , Quality Control , Reproducibility of Results , Staining and LabelingABSTRACT
Methylcitric acid (MCA) was synthesised in Reformatsky reaction (2RS, 3RS stereoisomers) and in the nucleophilic addition (2RS, 3SR stereoisomers). The stereoselectivity of these reactions was analysed. (1)H and (13)C NMR spectra of diastereoisomers of methylcitric acid were recorded and interpreted. The values of (1)H chemical shifts and (1)H-(1)H coupling constants were analysed. Proton-decoupled high-resolution (13)C NMR spectra of MCA diastereoisomers were measured in a series of dilute water solutions of various acidities. These data may provide a basis for unequivocal determination of the presence of MCA in the urine samples of patients' suffering from propionic acidemia, methylmalonic aciduria, or holocarboxylase synthetase deficiency. NMR spectroscopy enables determination of MCA diastereoisomers in body fluids and can be a complementary and useful diagnostic tool.
Subject(s)
Citrates/chemistry , Body Fluids/chemistry , Carbon Isotopes/analysis , Citrates/analysis , Citrates/chemical synthesis , Humans , Magnetic Resonance Spectroscopy , Protons , StereoisomerismABSTRACT
Described herein is a simple, flexible, and efficient synthesis of the skeleton of the viridiofungins, a family of microbial secondary metabolites. The synthesis utilizes an asymmetric aldol reaction of a chiral oxazolidinone, a diastereoselective alkylation of a chiral 1,3-dioxolan-2-one, and a geometrically selective alkene cross-metathesis reaction as the key C-C bond-forming steps.
Subject(s)
Amino Acids/chemistry , Citrates/chemistry , Alkylation , Catalysis , Citrates/chemical synthesis , Esters/chemistry , Malates/chemistry , Molecular StructureABSTRACT
Herein, we report the synthesis and evaluation of a novel family of biodegradable and elastomeric polyesters, poly(diol citrates). Poly(diol citrates) were synthesized by reacting citric acid with various diols to form a covalent cross-linked network via a polycondensation reaction without using exogenous catalysts. The tensile strength of poly(diol citrates) were as high as 11.15+/-2.62 MPa and Young's modulus ranged from 1.60+/-0.05 to 13.98+/-3.05 MPa under the synthesis conditions that were investigated. Elongation was as high as 502+/-16%. No permanent deformation was found during mechanical tests. The equilibrium water-in-air contact angles of measured poly(diol citrates) films ranged from 15 degrees to 53 degrees . The mechanical properties, degradation and surface characteristics of poly(diol citrates) could be controlled by choosing different diols as well as by controlling the cross-link density of the polyester network. Various types of poly(diol citrate) scaffolds were fabricated to demonstrate their processing potential. These scaffolds were soft and could recover from deformation. In vitro and in vivo evaluation using cell culture and subcutaneous implantation, respectively, confirmed cell and tissue compatibility. The introduction of poly(diol citrates) will expand the repertoire of currently available biodegradable polymeric elastomers and should help meet the requirements of tissue engineering applications.