Aliphatic Systems Research Articles

1H, 15N, 13C and 13CO assignments and secondary structure determination of basic fibroblast growth factor using 3D heteronuclear NMR spectroscopy.

The assignments of the 1H, 15N, 13CO and 13C resonances of recombinant human basic fibroblast growth factor (FGF-2), a protein comprising of 154 residues and with a molecular mass of 17.2 kDa, is presented based on a series of three-dimensional triple-resonance heteronuclear NMR experiments. These studies employ uniformly labeled 15N- and 15N-/13C-labeled FGF-2 with an isotope incorporation > 95% for the protein expressed in E. coli. The sequence-specific backbone assignments were based primarily on the interresidue correlation of C alpha, C beta and H alpha to the backbone amide 1H and 15N of the next residue in the CBCA(CO)NH and HBHA(CO)NH experiments and the intraresidue correlation of C alpha, C beta and H alpha to the backbone amide 1H and 15N in the CBCANH and HNHA experiments. In addition, C alpha and C beta chemical shift assignments were used to determine amino acid types. Sequential assignments were verified from carbonyl correlations observed in the HNCO and HCACO experiments and C alpha correlations from the HNCA experiment. Aliphatic side-chain spin systems were assigned primarily from H(CCO)NH and C(CO)NH experiments that correlate all the aliphatic 1H and 13C resonances of a given residue with the amide resonance of the next residue. Additional side-chain assignments were made from HCCH-COSY and HCCH-TOCSY experiments. The secondary structure of FGF-2 is based on NOE data involving the NH, H alpha and H beta protons as well as 3JHNH alpha coupling constants, amide exchange and 13C alpha and 13C beta secondary chemical shifts. It is shown that FGF-2 consists of 11 well-defined antiparallel beta-sheets (residues 30-34, 39-44, 48-53, 62-67, 71-76, 81-85, 91-94, 103-108, 113-118, 123-125 and 148-152) and a helix-like structure (residues 131-136), which are connected primarily by tight turns. This structure differs from the refined X-ray crystal structures of FGF-2, where residues 131-136 were defined as beta-strand XI. The discovery of the helix-like region in the primary heparin-binding site (residues 128-138) instead of the beta-strand conformation described in the X-ray structures may have important implications in understanding the nature of heparin-FGF-2 interactions. In addition, two distinct conformations exist in solution for the N-terminal residues 9-28. This is consistent with the X-ray structures of FGF-2, where the first 17-19 residues were ill defined.

Regiochemical control of the ring opening of 1:2-epoxides by means of chelating processes. 10. Synthesis and ring opening reactions of mono- and difunctionalized cis and trans aliphatic oxirane systems

The regiochemical outcome of the ring opening of 1:2-epoxides through chelation processes assisted by metal ions, was verified in mono- and difunctionalized aliphatic oxirane systems bearing the heterofunctionality (OR) in an homoallylic and/or allylic relationship to the oxirane ring. The effect of the distance of the OR functionality from the oxirane ring and of the type of protective group on the regiochemical outcome of these systems is examined. In some cases, the use of LiClO 4 or Mg(ClO 4)2 as the promoting metal salt makes it possible the obtainment of a nice regioalternating process.

Nitrogen NMR assessment of interactions between nitroso, cyano and acetyl groups across aliphatic systems

AbstractThe nitrogen NMR shieldings (Δσ, equivalent to —Δδ on the frequency scale of chemical shifts) of the NO group in nitrosoalkanes are shown to be a sensitive probe to electron‐withdrawing effects of substituents and to steric strain effects. The former produce high‐field (low‐frequency) shifts, which can amount to about 90 ppm, while the latter result in considerable low‐field (high‐frequency) shifts of the NO nitrogen resonance. The CN nitrogen shieldings show less pronounced low‐field (high‐frequency) shifts under the influence of electron acceptors. The signs and magnitudes of the observed effects are explained in terms of semi‐empirical molecular orbital calculations of the shieldings and molecular mechanics evaluations of strain energies. The overall picture of relationships between the NO and CN nitrogen shieldings and electron charge migration within the molecules concerned is in accord with that obtained in earlier studies of solvent‐induced effects on the nitrogen shieldings in alkyl cyanides and nitro compounds.

Enthalpic determinations of aliphatic ester-solvent systems with correlations

Calorimetric measurements were carried out on ester-solvent systems where the esters were H(CH2)xCOO(CH2)yH, with x and y varying from 1 to 5, and the solvents were n-hexane and 1,2-dichloroethane. Calculation of the enthalpies of cavity formation enabled the enthalpies of interaction to be determined. Both enthalpies correlated with number of carbon atoms N, equal to x+y in the esters, giving for 1,2-dichloroethane $$\begin{gathered} \Delta _{cav} H_m^O = 29.4 \pm 2.3 + 4.7 \pm 0.4N \hfill \\ \Delta _{int} H_m^O = - 53.9 \pm 2.5 - 8.2 \pm 0.5N \hfill \\ \end{gathered} $$ and for n-hexane $$\begin{gathered} \Delta _{cav} H_m^O = 8.8 \pm 1.1 + 3.4 \pm 0.2N \hfill \\ \Delta _{int} H_m^O = - 20.0 \pm 2.1 - 8.3 \pm 0.4N \hfill \\ \end{gathered} $$

Solubilization of Nicardipine Hydrochloride via Complexation and Salt Formation

The solubility behavior of nicardipine (1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 2-[methyl(phenylmethyl)amino]ethyl diester), a calcium channel blocker, used in the treatment of chronic stable angina and mild essential hypertension was investigated. Two techniques that are known to improve solubility, complexation and salt formation, were examined. Concentrations were determined with a specific reversed-phase HPLC assay. The solubility of nicardipine hydrochloride was enhanced exponentially via complexation with aliphatic carboxylic acid buffer systems in a pH dependent fashion. The solubility increased from 5 to 68.6 and 270 mg/mL as the acetate or propionate buffer concentrations, respectively, increased from 0.001 to 5 M, showing a positive deviation from linearity. The conversion of nicardipine hydrochloride to the phosphate salt resulted in a ∼10-fold solubility improvement. The surface tension of the nicardipine phosphate in water as a function of concentration indicated a critical micelle concentration of 5–6 mg/mL. The critical micelle concentration was greater than the equilibrium solubility of the hydrochloride salt in water, suggesting that a self-association phenomena is responsible for the enhanced solubility of the phosphate salt. Both routes provided potential alternatives for the solubilization of nicardipine.

3-(Methyleneaminoxy)methylpiperidine derivatives as uptake inhibitors of biogenic amines in the brain synaptosomal fraction

A series of 3-(methyleneaminoxy)methylpiperidines ( 5a–h) and their corresponding N-methyl derivatives ( 6a–h) with a variety of substituents on the imino carbon were synthesized and tested for their potential antidepressant properties; their capacity to inhibit the re-uptake of biogenic amines (NA, 5-HT and DA) in rabbit brain synaptosomal fractions was also evaluated. The biological results obtained for the piperidine derivatives 5a–h and 6a–h and viloxazine 1, the reference drug, on the 3 re-uptake systems revealed that compounds 5 and 6 are generally able to inhibit biogenic amine uptake. The IC 50 values for 5 and 6 were often lower than that of viloxazine 1, in particular for the serotonin- and/or dopamine-uptake systems. A higher activity was found for compounds substituted with at least one phenyl ring on the imino carbon with respect to completely aliphatic systems, and for N-unsubstituted compounds with respect to N-methyl-substituted compounds.

New Macrocyclic Ligands. V. Synthetic, Crystallographic and Computational Studies of a New N2O6-Heteroatom Cage

The synthesis, characterization and X-ray structure of a new cage molecule containing six phenoxy and two nitrogen heteroatoms is reported. Semiempirical MO calculations have been used to probe the topological rigidity of the cage relative to related aliphatic systems.

Sequential assignment of proton resonances in the NMR spectrum of Zn-substituted alpha chains from human hemoglobin. Ligand-induced tertiary changes in the heme pocket.

We constructed an artificial holoprotein as a complex between alpha globin from human adult hemoglobin and the protoporphyrin IX-Zn(II). The prosthetic group is bound in a single conformation to the apoglobin via a coordinative bond between Zn(II) ion and the proximal histidine (His87). The complex is diamagnetic and does not bind either CO nor O2 thus representing a diamagnetic model of deoxygenated alpha chains. In the present paper we report extensive resonance assignment in the proton nuclear magnetic resonance spectrum of the Zn-substituted alpha chains in phosphate buffer pH 5.6. A large number of aromatic and aliphatic side chain spin systems were identified in the two-dimensional homonuclear COSY spectra. Based on the assigned resonances of heme substituent protons and their NOE cross-peaks, we assigned the majority of resonances representing the heme pocket side chains. Using the main-chain-directed assignment strategy, we could establish several continuous patterns of sequential assignment and identify partial or total spin systems for a large number of side chains. The final assignment corresponds to 73% of the amino acids. Analysis of chemical shift of assigned resonances and of nuclear Overhauser enhancement connectivities provides structural information on the global and local tertiary conformation in solution and on the ligand-induced conformational changes. Comparison of observed and calculated ring current shifts enabled us to compare the solution structure with the X-ray crystal structure of alpha subunits in deoxy and carbonmonoxy hemoglobin. The global tertiary structure of unliganded chains is highly similar to both ligand and unliganded counterparts in the crystalline state. On the distal side of the heme pocket. Val62 is significantly closer to the heme center, in agreement with its conformation in the crystallographic structure. In contrast, the position of the proximal histidine (His87) relative to the heme is clearly more closely related to that in the liganded tetramer in the crystalline state. Comparison of the chemical shift values for the resonances in carbon monoxy and Zn(II)-substituted alpha chains indicates that the ligand-induced conformational changes are essentially localized in the heme pocket area and affect proximal side residues more than the distal side ones. Some notable spectral changes are discussed in connection with the crystallographic data and their relevance for the functional mechanism.

Quantitative lattice measurement of thin Langmuir-Blodgett films by atomic-force microscopy.

We have quantitatively determined the nature of the surface order of the outermost layer of monolayer and multilayer Langmuir-Blodgett films of cadmium arachidate, in air and under water, using atomic-force microscopy. Molecular-resolution images of 1200-${\mathrm{nm}}^{2}$ areas show that the alkyl chains of 2--5-layer films have a noncentered rectangular lattice with lattice constants of 0.482\ifmmode\pm\else\textpm\fi{}0.004 and 0.748\ifmmode\pm\else\textpm\fi{}0.006 nm, in good agreement with diffraction measurements of bulk aliphatic systems. We show unambiguously that the unit cell consists of two molecules. In contrast with the highly ordered multilayers, monolayer films have a disordered surface. Images taken under water of the head-group surface show that the bilayer surface is disordered, while thicker films show order of the alkyl chains. The presence of an underlying head-group--head-group interface with its associated cadmium ion bridging is shown to be the critical feature needed to obtain a stable and ordered surface layer.

100% Solids Aliphatic Spray Polyurea Elastomer Systems

Regulations are continually being passed that limit the volatile organic content (VOC) of elastomer coating systems. Because of this restriction, high solids, two-component spray elastomers and coatings are attaining in creases in market interest and sales volume. As this interest grows, the research and development effort focuses on newer and better polymer materials. The development of 100% solids aromatic polyurethane elastomer systems has shown promise with respect to the VOC issues. Recently, a further refined 100% solids spray elastomer system, based on polyurea RIM technol ogy, has also been demonstrated. These systems, like polyurea RIM materials, are based on aromatic isocyanates, aromatic amine chain extenders and amine- terminated polyether resins. In order to take full advantage of the leading edge polyurea elastomer technology, 100% solids aliphatic polyurea elastomer systems have been developed. Amine-terminated polyether resins along with aliphatic isocyanates are incorporated into this next generation of spray elastomer materials. Aliphatic spray polyurea elastomer systems, like the aromatic polyurea elastomer systems, require no catalysts and are extremely fast in reactivity and cure. Due to this fast reactivity and cure, these systems are virtually unaf fected by moisture during processing. Application of the aliphatic polyurea systems is also possible in a variety of temperature ranges with little effect on the reaction profile and cure. Any VOC standards or regulations are easily com plied with due to the 100% solids characteristic. Excellent elastomer physical properties are also noted at varied temperature ranges. Obviously, spray elastomer systems based on this aliphatic polyurea technology are good candi dates for both coating and noncoating-type applications. Recent advances in the aliphatic spray polyurea elastomer technology will be discussed in this paper.

1H, 15N, 13C, and 13CO assignments of human interleukin-4 using three-dimensional double- and triple-resonance heteronuclear magnetic resonance spectroscopy.

The assignment of the 1H, 15N, 13CO, and 13C resonances of recombinant human interleukin-4 (IL-4), a protein of 133 residues and molecular mass of 15.4 kDa, is presented based on a series of 11 three-dimensional (3D) double- and triple-resonance heteronuclear NMR experiments. These studies employ uniformly labeled 15N- and 15N/13C-labeled IL-4 with an isotope incorporation of greater than 95% for the protein expressed in yeast. Five independent sequential connectivity pathways via one-, two-, and three-bond heteronuclear J couplings are exploited to obtain unambiguous sequential assignments. Specifically, CO(i)-N(i + 1),NH(i + 1) correlations are observed in the HNCO experiment, the C alpha H(i), C alpha (i)-N(i + 1) correlations in the HCA(CO)N experiment, the C alpha(i)-N(i + 1),NH(i + 1) correlations in the HNCA and HN(CO)CA experiments, the C alpha H(i)-N(i + 1),NH(i + 1) correlations in the H(CA)NH and HN(CO)HB experiments, and the C beta H(i)-N(i + 1),NH(i + 1) correlations in the HN(CO)HB experiments. The backbone intraresidue C alpha H(i)-15N(i)-NH(i) correlations are provided by the 15N-edited Hartmann-Hahn (HOHAHA) and H(CA)NH experiments, the C beta H(i)-15N(i)-NH(i) correlations by the 15N-edited HOHAHA and HNHB experiments, the 13C alpha(i)-15N(i)-NH(i) correlations by the HNCA experiment, and the C alpha H(i)-13C alpha(i)-13CO(i) correlations by the HCACO experiment. Aliphatic side-chain spin systems are assigned by 3D 1H-13C-13C-1H correlated (HCCH-COSY) and total correlated (HCCH-TOCSY) spectroscopy. Because of the high resolution afforded by these experiments, as well as the availability of multiple sequential connectivity pathways, ambiguities associated with the limited chemical shift dispersion associated with helical proteins are readily resolved. Further, in the majority of cases (88%), four or more sequential correlations are observed between successive residues. Consequently, the interpretation of these experiments readily lends itself to semiautomated analysis which significantly simplifies and speeds up the assignment process. The assignments presented in this paper provide the essential basis for studies aimed at determining the high-resolution three-dimensional structure of IL-4 in solution.

13C NMR substituent effects in aliphatic systems: Principal component analysis and correlations with electronegativities

AbstractPrincipal component (PC) or factor analysis was applied to 13C substituent effects (literature SCS values) in α to δ positions of 47 aliphatic frameworks with 4–13 different substituents X. Two PC terms for each substituent X are sufficient to describe 99.3% of all C‐α shifts within < ± 0.6 ppm, even in the largest data matrix containing 13 × 47 = 611 shifts; shifts in β. γ and δ positions require a third PC term for a similar percentage SCS accuracy. Scaling problems with the different order of magnitudes between α to δ SCS variations are avoided by analysing the corresponding data sets separately; this approach, together with the large data base, leads to a dominating first PC term for C‐α which unambiguously correlates with substituent electronegativities (EN), in contrast to an earlier factor analysis. The same result is obtained by direct comparison of α‐SCS with different EN scales, including for the first time group electronegativities. PCs for β to γ SCS indicate only less consistent trends, which again agree partially with results from direct correlations, but not with EN values. The present PC analysis did not include stereochemical descriptors, but furnishes clear distinctions between clusters of (pseudo‐) equatorially or axially substituted compounds. The PC loadings for C‐α also lead to the unambiguous distinction of primary, secondary, tertiary and quaternary carbon atoms.

Synthesis of perfluoroalkylthioethers from disulfides

Perfluoroalkylthioethers are synthesized from disulfides and freons, halons or halogenoperfluoroalkanes according to: 2R FX + 2Red+ RSSR → 2R FSR + 20x This reaction was studied with aliphatic, aromatic and heteroaromatic disulfides Several reductor systems have been used. They behaved as sulfur dioxide-radical anion precursors. The initial step is interpreted by single electron transfer from this radical anion to the halide. The mechanism will be discussed. Halogenoalkylthioethers groups are very lipophilic and interesting as substituents for pharmaceutical drugs and agrochemical compounds.

Sterically Hindered Internal Rotation in an Acyclic α,β‐Unsaturated Ketone. 2, 2, 5‐Trimethyl‐4‐isopropylhex‐4‐en‐3‐one

An activation barrier of 45 kJ mol−1 follows from the 1H-NMR spectra in the case of the first detected hindered rotation about the sp2—sp2 single bond of an acylic α,β-unsaturated ketone (1). The intensities of the UV bands of the π→π* and n → π* transitions are consistent with a skewed conformation of 1. However, molecular mechanics calculations predict a much higher steric barrier than is observed, which demonstrates the limitations of our current understanding of sterically hindered rotation about sp2—sp2 single bonds in aliphatic systems.

Association of ethanol in inert solvents

The previously derived association model is extended to account for cyclic multimers. If applied for ethanol + aliphatic hydrocarbon systems at low alcohol concentrations it predicts spectroscopic and calorimetric properties without any adjustable parameters better than other approaches do. It also provides more reliable values of the chemical contribution to the heats of mixing for the whole composition range.

Comparison between some semi‐empirical and ab initio Hartree–Fock models for the description of amides (formamide revisited)

AbstractA comparative study on the use of the MINDO/3, MNDO and AM1 semi‐empirical methods for the description of formamide and aliphatic amide systems is reported. For formamide, ab initio Hartree–Fock calculations are also reported using both the STO‐3G and 3–21G basis sets, as well as a basis set obtained by a minimal relaxation of the STO‐3G contraction scheme. It is shown that both the MNDO and the STO‐3G methods cannot properly reproduce the experimental results. In both cases this appears to be due to inadequacies of the basis sets used. Again in both cases only small improvements in the basis set necessary to allow for the diffuse character of the pπ orbitals lead to dramatic improvements in the calculated results. In the case of the STO‐3G basis set this is demonstrated by the fact that a small relaxation in the contraction leads to results even superior to those with the 3–21G set. The conclusions reached for amide systems can be extended to other systems where planarity around or inversion with respect to nitrogen is an issue. This is demonstrated for ammonia.

Coal liquefaction in primary aliphatic amine systems

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCoal liquefaction in primary aliphatic amine systemsWei Yin Chen and Faheem M. KazimiCite this: Ind. Eng. Chem. Res. 1990, 29, 7, 1109–1119Publication Date (Print):July 1, 1990Publication History Published online1 May 2002Published inissue 1 July 1990https://doi.org/10.1021/ie00103a004RIGHTS & PERMISSIONSArticle Views65Altmetric-Citations3LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-Alerts Get e-Alerts

ChemInform Abstract: Anomalous Energy Effects in Some Aliphatic and Alicyclic Aza Systems and Their Nitro Derivatives.

ChemInformVolume 21, Issue 26 Physical Organic Chemistry ChemInform Abstract: Anomalous Energy Effects in Some Aliphatic and Alicyclic Aza Systems and Their Nitro Derivatives. J. S. MURRAY, J. S. MURRAY Dep. Chem., Univ. New Orleans, New Orleans, LA 70148, USASearch for more papers by this authorP. C. REDFERN, P. C. REDFERN Dep. Chem., Univ. New Orleans, New Orleans, LA 70148, USASearch for more papers by this authorJ. M. SEMINARIO, J. M. SEMINARIO Dep. Chem., Univ. New Orleans, New Orleans, LA 70148, USASearch for more papers by this authorP. POLITZER, P. POLITZER Dep. Chem., Univ. New Orleans, New Orleans, LA 70148, USASearch for more papers by this author J. S. MURRAY, J. S. MURRAY Dep. Chem., Univ. New Orleans, New Orleans, LA 70148, USASearch for more papers by this authorP. C. REDFERN, P. C. REDFERN Dep. Chem., Univ. New Orleans, New Orleans, LA 70148, USASearch for more papers by this authorJ. M. SEMINARIO, J. M. SEMINARIO Dep. Chem., Univ. New Orleans, New Orleans, LA 70148, USASearch for more papers by this authorP. POLITZER, P. POLITZER Dep. Chem., Univ. New Orleans, New Orleans, LA 70148, USASearch for more papers by this author First published: June 26, 1990 https://doi.org/10.1002/chin.199026063Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume21, Issue26June 26, 1990 RelatedInformation

Anomalous energy effects in some aliphatic and alicyclic aza systems and their nitro derivatives

Abstract : We have used an ab initio Self Consistent Field (SCF) molecular orbital approach in conjunction with the isodesmic reaction procedure to investigate anomalous energy effects in aliphatic and alicyclic aza systems. These molecules are found to be significantly stabilized, which we attribute to sigma-conjugation of the nitrogen lone pairs; these are presumably delocalized to some extent through the sigma-bond framework. The stabilization increases with the number of nitrogens in a series of similar molecules and is greater in cyclic systems, particularly when rings are fused. The magnitudes of the most negative electrostatic potentials of the aza nitrogens, which can be viewed as indicating the degrees of delocalization of the nitrogen lone pairs, decrease as the added stability increases. In these systems, the introduction of nitro groups also has an overall stabilizing effect, which may be due to further delocalization of sigma-electrons, reflecting the strong electron-withdrawing power of the nitro group. (KT)

Stereocontrolled preparation of cyclohexane amino alcohols utilising a modified Mitsunobu reaction

A method for the introduction of amino groups into aliphatic systems is described. Cyclohex-2-enol reacts with aromatic diacylamines under Mitsunobu reaction conditions to give either N-alkylated or O-alkylated products in a controlled, predictable manner. The product cyclohexenes, with N-bromosuccinimide, give either 1,2- or 1,3-neighbouring group participation leading to 1,2,3-trisubstituted cyclohexanes. The adducts may be used to give a range of 1,2- and 1,3-amino alcohols in a stereocontrolled process.