Isocyanate Derivatives Research Articles

Fluorescence Determination of Microconcentrations of Chlorambucil after Photoactivation

A fluorescence assay is described which measures the alkylating activity of chlorambucil or its isocyanate derivative after photoactivation in the presence of dimethyl sulfoxide. This assay has a lower limit of sensitivity of 100 ng/mL and RSD of <10% for chlorambucil. The method requires >5 μg of alkylating agent and the fluorophore produced is stable for at least 24h.

A chlorambucil-anti-CEA conjugate cytotoxic for human colon adenocarcinoma cells in vitro.

The use of chlorambucil (CBL) for the chemotherapeutic treatment of cancer is often limited because of undesirable side effects due to its lack of specificity for cancer cells. Systemic effects such as renal toxicity, marrow aplasia, pulmonary fibrosis and gastrointestinal disorders may be eliminated or greatly reduced by increasing the specificity of the drug towards tumour cells. Carcinoembryonic antigen (CEA), an oncofoetal protein produced by some human cancer cells (Gold & Friedman, 1965), is extensively used as a clinical cancer marker for the follow-up of treated patients. We have already reported that this protein could be a target for daunorubicin-anti-CEA conjugates (Belles-Isles & Page, 1981; Page et al., 1981). Many authors have already described a method to adsorb chlorambucil to antitumour antibodies (Blakeslee & Kennedy,1974; Guclu et al., 1976), but in the previous applications of chlorambucilantibody conjugates, a certain percentage of the reported activity could have been due to the presence of a non-covalently bound aggregate of the drug (Blakeslee et al., 1975). The other method described for the covalent coupling of CBL (Tai et al., 1979) could lead to polymerisation of the carrier and needed a 2 h incubation in an aqueous solution. We present here a new method for the covalent binding of chlorambucil which allows a rapid coupling to proteins without any significant polymerisation. This was obtained using the isocyanate derivative of chlorambucil: 3-{4-[bis(2chloroethyl)amino]phenyl}propyl-1-isocyanate. The conjugate was separated from the remaining free drug by gel filtration on Sephadex G-25 (Pharmacia Fine Chemicals) and the drug:protein ratio was determined by a photofluorometric method to assay the alkylating activity of CBL (Bernier et al., 1983). This ratio could be varied by mixing various proportions of the drug derivative and of the antibody; in the assay conditions reported a ratio of 25 moles of drug per mole of antibody was used. The cytotoxic effects of chlorambucil-anti-CEA conjugates on LoVo cells (CEA producing human colon carcinoma cells) were evaluated by the inhibition of colony formation as already described (Emond & Page, 1982). Figure 1 illustrates that for any concentration of drug used, the highest inhibition of colony formation was obtained with the covalent drug-antibody conjugate. Also the antibodies were neither cytolytic nor cytostatic for these cells in vitro. The concentration required to obtain a 50% inhibition of colony formation (ID 50) was much lower for the conjugate than for the free drug, the physical mixture of both agents or chlorambucil conjugated to non-specific antibodies (anti-alphafoetoprotein). Experiments on non-CEA producing cells (CCL6; human amnions) showed the specificity of the CBL-anti-CEA conjugate for CEA producing cell lines (Table I). The contact period study (Figure 2) shows that a rapid binding of the CBL-anti-CEA conjugate allows a much higher pharmacological activity when compared to equimolar concentrations of the free drug.

Mass Spectrometric and IR Analysis of Deuterium Content of Water Using an Isocyanate Derivative.

Formation d'uree (diphenyl-1,3) par reaction d'une goutte d'echantillon d'eau lourde et de l'isocyanate de phenyle dans du diethyl ether

Determination of aliphatic amines in air by reversed-phase high-performance liquid chromatography using 1-naphthyl isocyanate derivatives

Determination de traces de n-propylamine, n-butylamine et allylamine dans l'air sous forme de derives d'isocyanate de naphtyl-1

Improved chromatographic procedure for determination of 9-(N-methylaminomethyl)anthracene isocyanate derivatives by high-performance liquid chromatography

Improved chromatographic procedure for determination of 9-(N-methylaminomethyl)anthracene isocyanate derivatives by high-performance liquid chromatography

Synthesis and spectra of new 3‐carbethoxypyrazole sulfonylurea derivatives

AbstractThe reaction of 1‐benzenesulfonyl‐3‐ethoxycarbonyl‐5‐[α‐substituted‐styryl]pyrazoles (1) with isocyanate and thioisocyanate derivatives yield the corresponding benzenesulfonylurea derivatives (2 and 3). Bromination of 1 afforded the 4‐bromopyrazoles 4 which react with isocyanate derivatives giving 5 that were also obtained by bromination of 2. Alkaline hydrolysis of the benzensulfonylurea derivatives 2 yield the corresponding pyrazole‐3‐carboxylic acids 7.

15N NMR spectroscopy, 27. Spectroscopic characterization of polyurethanes and related compounds

AbstractNatural abundance 15N and 13C NMR spectra of various polyurethanes were measured in trifluoroacetic acid. The polyurethanes were built up from aliphatic diols, polyesters of diols or oligoethylene glycols on the one hand, and from aliphatic α,ω‐diisocyanates or aromatic diisocyanates, on the other hand. In addition to the polyurethanes various low molecular weight model compounds, such as ureas, biurets, allophanic acid esters, uretdions and 1,3,5‐triazinetriones, were investigated. The substituent effects of phenyl groups in the above mentioned compounds were studied in various solvents. 15N NMR spectra were found to be more useful than 13C NMR spectra for the identification of the various isocyanate derivatives, while 13C NMR spectra have the advantage of a better signal‐to‐noise ratio.

Methylisocyanate as an antisickling agent and its reaction with hemoglobin S.

Reviewing the reaction of potassium cyanate, an antisickling agent, with alpha-amino groups of hemoglobin, it was found that the reaction was a slow process and requires a large excess of the reagent. The reason for the slow reaction rate of carbamylation of hemoglobin by cyanate is that cyanate itself does not react with hemoglobin. It is rather isocyanic acid, the reactive species, that reacts with hemoglobin. Since the pK of isocyanic acid is 3.8, only one out of 4,000 cyanate ions is present as isocyanic acid at physiological pH. Therefore, it appears that a large excess of cyanate ions is required to achieve the carbamylation of hemoglobin S, both in vivo and in vitro. Furthermore, the pH optimum for carbamylation of carboxyhemoglobin and deoxyhemoglobin is 5.5 and, at pH 7.4, the reaction velocity drops to one-third for carboxyhemoglobin and one-half for deoxyhemoglobin. To seek an approach to reduce the dosage of cyanate and to increase the reaction velocity, an isocyanate derivative, methylisocyanate which is already in the reactive form, was tested for its antisickling activity and its reaction with hemoglobin S. It was found that methylisocyanate had antisickling activity and that only a stoichiometric amount to 2-fold excess of the reagent over hemoglobin S alpha-amino groups was required to prevent the sickling of erythrocytes. Methylisocyanate-treated sickle erythrocytes showed an increased oxygen affinity compared to untreated methylisocyanate reacted with alpha-amino groups of hemoglobin S and the reaction was complete in less than 1 min. Methylcarbamylated hemoglobin S had a higher minimum gelling concentration than the untreated hemoglobin S. There was no detectable reaction of free sulfhydryl and epsilon-amino groups of hemoglobin S with methylisocyanate. These results indicate that methylisocyanate, and probably other isocyanate derivatives, possesses powerful antisickling activity.

Isocyanate, urea and amide complexes from the reactions of organic azides with low oxidation state complexes of transition metals

The reactions of organic azides RN 3 (R = p-CH 3C 6H 4SO 2, p-CH 3C 6H 4CO, C 6H 5CO, 2-carbonylfuran) with Ru(CO) 3(PPh 3) 2 in benzene have been studied. Isocyanate, Ru(CO) 2(PPh 3) 2(RNCO), urea, Ru(CO) 2(PPh 3) 2(RNCONR) or amide, Ru(CO) 2(PPh 3) 2(NHR) 2, derivatives were obtained, depending on the reaction conditions and on the nature of R. The urea complex (R = p-CH 3C 6H 4SO 2) was also obtained by the oxidative addition of N, N′-ditoluene- p-sulphonyl urea or toluene- p-sulphonyl isocyanate to Ru(CO) 3(PPh 3) 2. The isocyanate derivative with R = C 6H 5CO was found to be protonated by fluoboric acid to give the corresponding carbamoyl complex, [Ru(CO) 2(PPh 3) 2(CONHR)] +BF 4 − which on treatment with LiCl gave the non-ionic derivative, [Ru(CO)(PPh 3) 2(CONHR)Cl] n . Analogous reactions were studied with the complexes Ru 3(CO) 9L 3 (L = CO, PPh 3), but the only characterizable product was the monomeric Ru(CO) 2L 2(RNCONR) (L = PPh 3, R = p-CH 3C 6H 4SO 2). Attempted cycloaddition reactions in benzene of the azides to coordinated ligands L other than carbon monoxide, such as CS 2, PhNCS, alkenes, in the complexes Pt(PPh 3) 2L or SO 2 in Pt(PPh 3) 3SO 2 were unsuccesful. Only in protic solvents was a clean reaction observed (L = CH 2CHCN), leading to the known complex Pt(PPh 3) 2(N 3)(NHR) (R = p-CH 3C 6H 4SO 2). Similarly, the complexes Pd(LL)(dba) (LL = 2,2′-bipyridyl, o-phenanthroline, dba = dibenzylideneacetone), on treatment with RN 3 in ethanol gave the new amide derivatives, Pd(LL)(X)(NHR), (X = NHR, R = p-CH 3C 6H 4SO 2; X = N 3, R = p-CH 3C 6H 4CO).

Studies on Pyrimidine Derivatives and Related Compounds. LXXX. Unusual Reactions of Thiamine Free Base with Electrophilic Reagents. (2)

The reaction of thiamine free base (I) with isocyanate derivatives in polar solvent such as dimethylformamide afforded 2- (7-methyl-3, 4-dihydropyrimido [4, 5-d] pyrimidin-3-yl) -2-methyltetrahydrofuran-3-yl alkyl (aryl) carbamthiolate (V), which then reacted with another isocyanate molecule to give N-carbamoylthiamine free base (II). The reaction mechanism is discussed kinetically. The reaction of I with isocyanate derivatives in less polar solvent such as chloroform afforded only II-analogues. The reaction of II with N, N-disubstituted carbamoylchlorides afforded 2- [N-formyl-N- (2-methyl-4-aminopyrimidin-5-yl) methyl] amino-2-methyltetrahydrofuran-3-yl disubstituted carbamthiolates (VIIa-c).

Identification of hydroxamic acids by gas chromatography of isocyanate derivatives

A method is described for the analysis of hydroxamic acids. The hydroxamic acids are initially quantitatively acetylated by treatment with excess acetic anhydride and pyridine. This reaction mixture is applied directly to a gas chromatographic column. On the column the hydroxamate esters are quantitatively converted to isocyanates which are readily separated by gas chromatography. An example is given of the analysis of a mixture of acyl CoA compounds by converting them to hydroxamic acids and identifying the latter by gas chromatography of their isocyanate derivatives.

STUDY OF OCTADECYL ISOCYANATE DERIVATIVES

Reactions of octadecyl ethylene urea and water-repellent effect of derivatives of octadecyl isocyanate were studied.Octadecyl ethylene urea reacted with nucleophilic agents openning the ethylene imino ring at lower temperature, while at higher temperature it reacted as octadecyl isocyanate which was formed by the decomposition of octadecyl ethylene urea. It was supposed that the reactions of the above two types with cellulose would proceed, when cellulose treated with octadecyl ethylene urea was cured.As octadecyl isocyanate derivatives, N-octadecyl phenyl urethane, sodium bisulfite adduct, octadecyl urea, dioctadecyl urea and octadecyl isocyanate trimer were prepared. It was found that these derivatives reacted with cellulose at higher temperature as octadecyl isocyanate which was formed by the thermal decomposition, and accordingly viscose rayon fabrics treated by the derivatives had water-repellent property. But the water-repellency was not so remarkable.

The Reactions of Isocyanates and Isocyanate Derivatives at Elevated Temperatures

Abstract Qualitative and quantitative studies with model compounds have shown that a variety of reactions may occur at 100–300° in molecules containing isocyanate, urea and urethane groups. All or most of these reactions are subject to catalysis so that they may be induced to proceed at lower temperatures. These reactions are quite important as they may affect the production and practical use of polyurethanes and polyureas. By the proper selection of reaction components one may design a polyurethane or polyurea molecule which will give both a reasonable rate of cure to the final state and a degree of temperature stability suitable for many rigorous applications. The choice of reactive groups providing approximately the desired rates of reaction and of suitable catalysts may be used to achieve the necessary curing rate. The initial choice of a catalyst which will have a minimum effect on decomposition reactions, or the removal of the catalyst from the cured polymer will favor polymer stability. A selection of reactants which will minimize those decomposition reactions leading to chain rupture, and which will compensate for what rupture may occur, will promote polymer stability. Simple illustrations of such choices would include eliminating tertiary aliphatic hydroxyl groups from the hydroxyl-bearing component and including some degree of branching commensurate with the degree of elasticity or rigidity desired. Branching should be achieved through the more stable groups, e.g., urethane, urea or trimer, rather than through the less stable allophanate and biuret groups. Many thoroughly tested applications of polyurethanes and mixed polyureaurethanes show that it is readily possible to produce such polymers with excellent thermal stability.

The α-Naphthyl Isocyanate Derivative of n-Butylaniline1

The α-Naphthyl Isocyanate Derivative of n-Butylaniline¹

Phenyl Isocyanate Derivatives of Certain Alkylated Phenols. Melting Points and X-Ray Powder Diffraction Data

Phenyl Isocyanate Derivatives of Certain Alkylated Phenols. Melting Points and X-Ray Powder Diffraction Data

Histamine-Protein Complexes: Synthesis and Immunologic Investigation

Summary A synthetic antigen was prepared by coupling the isocyanate derivative of histamine with despeciated horse serum globulin. The immunologic properties of the antigen were studied. The antiserum gave cross-reactions with histamine-azo-proteins, and the precipitative reaction was inhibited by histamine and by β-(5-Imidazolyl) ethyl isocyanate. Protection against symptoms of anaphylaxis in guinea-pigs after immunization with the complex was demonstrated by both in vivo and in vitro experiments.

ON LYSINE AND ORNITHINE

SUMMARY It is shown that significant amounts of ornithine and lysine may be precipitated by silver nitrate and sodium hydroxide. The formation of phenylhydantoins from phenyl isocyanate derivatives of ornithine and lysine by the action of acid is shown to be accompanied by racemization. Conditions are indicated by which racemization may be limited and optically homogeneous products obtained having definite melting points. BIBLIOGRAPHY 1. Kossel, A., Z. physiol. Chem., 26, 177 (1898). 2. Hedin, S. G., 2. physiol. Chem., 21, 297 (1895-96). 3. Dakin, H. D., Biochem. J., 12, 307 (1918). 4. Herzog, R. O., Z. physiol. Chem., 34,525 (1902). 5. Kossel, A., and Dnkin, H. D., Z. physiol. Chem., 41, 321 (1904). 6. Fischer, E., and Weigert, F., Ber. them. Ges., 36, 3772 (1902). 7. Sijrensen, S. P. L., Compt.-rend. trav. Lab. Curlsberg, 6, 209 (1905). 8. Dakin, H. D., and Dudley, H. W., J. Biol. Chem., 17,29 (1914).