Isopropyl Moiety Research Articles

Thermodynamics of multiple stimuli-responsive polyelectrolytes with complexing ability towards the copper(II) ion

The thermodynamics of protonation of carboxylate groups in polymers containing amido and isopropyl moieties was studied in 0.1 M NaCl at different temperatures. Compared with polymers with the l-leucine moiety, poly(N-acryloyl- l-valine) showed a wider decreasing linearity of the basicity constant (log K) in relation to the degree of protonation (α), with a minimum at α = 0.65. Under these conditions, a sharp endothermic peak revealed the presence of hydrophobic interactions as the macromolecule assumed a compact coil conformation and water molecules were released with an increase in entropy. The graft polymers on the surface of a polyurethane film displayed larger potentiometric hysteresis loops with respect to the cellulose support, as the nature of the polymer was similar to that of the hydrophobic substrate. The reversible configuration of the graft polymer chains instantly responded to changes in pH and temperature, modifying the rate of water filtration through the membrane pores. As the temperature approached 31°C an abrupt increase in water permeation was observed even though the graft polymer was in the uncharged and coiled state. The polyelectrolyte formed a hydroxo-complex species, involving two monomer units (L −) of the polymer, with the Cu(II) ion. Electron paramagnetic resonance (EPR) spectra, supported by conductometric data, revealed Cu(OH) 2L 2 2− stoichiometry in solution. The potentiometric data showed a good fit when processed by the Superfit program and a decreasing pattern of log β in relation to pH.

Molecular characterisation of neuropathy target esterase: Proteolysis of the [ 3H]DFP-labelled polypepide

Neuropathy target esterase (NTE) in hen brain membranes can be labelled with tritiated di-isopropylfluorophosphate ([ 3H]DFP) and appears to be associated with a 155-kDa polypeptide. Using preparative SDS-PAGE, we have obtained preparations in which [ 3H]DFP-labelled NTE comprises 2% of the total protein. Further purification of the 155-kDa polypeptide has proved difficult. We therefore attempted to use proteases to excise smaller [ 3H]DFP-labelled fragments which might be more amenable to fractionation. V8 protease treatment generated a labelled fragment of about 16 kDa which could be fractionated on SDS-PAGE and contained tritium attached to both site X (putatively the active site serine) and site Z (the residue to which an isopropyl moiety is transferred during aging of [ 3H]DFP-inhibited NTE). Papain and thermolysin treatments generated a small labelled peptide (<10 kDa) which could be fractionated on reverse-phase HPLC and in which tritium was attached to site X but not site Z. N-terminal sequencing of the thermolysin-generated peptide fraction indicated sample heterogeneity but also suggested that the active site of NTE may contain the serine esterase consensus sequence: Gly-Glu-Ser-Xxx-Gly.

Conformational studies by dynamic NMR. Part 48. Conformational preferences and stereomutational processes of the rotational enantiomers of hindered naphthylimines and imonium salts

A number of 1-naphthylimines (and some of the corresponding imonium chlorides), having the isopropyl group as a prochiral probe, have been synthesized and their configurations assigned by the combined use of NOE experiments and molecular mechanics calculations. This method also provides reliable information about the conformations adopted in solution. The existence of diastereotopic methyl groups in the isopropyl moiety indicates the presence of conformational enantiomers, due to the rotation about the naphthyl–imino bond in nonplanar conformers. The barriers for the stereomutation of such enantiomeric forms have been determined by line-shape analysis of the temperature-dependent 1H or 13C signals of the prochiral probe. Molecular mechanics calculations have also helped in suggesting which is the preferred stereomutation pathway and in predicting the existence of a derivative having configurationally stable enantiomers. Such a compound has been synthesized and is found to display the predicted property (atropisomerism), in that the two enantiomers can be separated.

Crystal structure of rosmanol-9-ethylether

The title compound: 2H-10,4a-(epoxy-methano)-phenantren-12-one-1,3,4,9,10,10a-hexahydro-5,6-dihydroxy-9α-etoxy-1,1-dirnethyl-7-(1-methylethyl), was isolated fromSalvia officinalis L. andHyssopus officinalis L. C22H30O5, orthorhombic, P212121, (No. 19)a=8.309(1),b=11.320(2),c=22.060(3) A,V=2075.0(9) A3,Z=4,D x=1.199 g·cm−3, λ(CuKα)=1.54184 A,μ=6.43 cm−1, F(000)=808,T=296(1) K. The structure was solved by direct methods and refined toR=0.047 for 1824 observed reflections collected on a CAD-4 diffractometer. In the course of structure refinement conformational disorder of the isopropyl moiety and the terminal methyl group pertaining to the ethoxy ligand was established. They result altogether in four different conformers.

Vibrational spectra and structure, ab initio calculations, and conformational stability of 2-methylpropanal

The Raman spectra (3600-10 cm −1) of gaseous, liquid and solid and the infrared spectra (3600- 40 cm −1) of gaseous and solid 2-methylpropanal (isobutyraldehyde), (CH 3) 2CHCHO, and the corresponding deuterium compound (CD 3) 2CDCHO have been recorded. Additionally, qualita- tive depolarization ratios have been obtained from the Raman spectra of the liquids. These data have been interpreted for the fluid phases, showing that the gauche conformation (oxygen atom eclipsing a methyl group) is thermodynamically preferred over the high energy trans conformation (oxygen atom eclipsing the secondary hydrogen) and is the only rotamer present in the spectra of the annealed solids. From the relative intensities of the Raman lines of the liquid at 633 cm −1 (gauche) and 551 cm −1 (trans) as a function of temperature, the enthalpy difference is found to be 440±17 cm −1 (1.26±0.05 kcal mol −1). Utilizing rotational constants from previously reported microwave data and structural parameters obtained from ab initio calculations, the r 0 structural parameters are reported for both rotameric forms. The ab initio and r 0 structures for the gauche conformer are consistent with nonequivalent CC bond distances for the isopropyl moiety. A complete vibrational assignment is proposed which is based on infrared band contours, depolarization values, isotopic shifts and group frequencies. The structural parameters, conformational stabilities, barriers to internal rotation, and fundamental vibrational frequencies which have been determined experimentally are compared to those obtained from ab initio Hartree-Fock gradient calculations utilizing both the 3-21G and 6-31G* basis sets, and to the corresponding quantities obtained for some similar molecules.

Investigation of the geometry of substituted dinitroanilines. I. Structural study of N,N-diisopropyl-2,4-dinitroaniline in the solid state and in solution

C15H21N304, monoclinic, P21/n, Mr = 307.3, a = 11.601 (6), b = 1t.223 (4), c = 12.143 (4) A, fl = 97.75 (2) °, V = 1567 (2) A 3, Z= 4, Dx = 1-30 g cm -3, Mo Ka radiation, A = 0.71073/~, /z = 0.89 cm- 1, F(000) = 656, room temperature, final R=0-043, wR=0.051 for 1948 observed independent reflections. The molecule in the solid state is significantly non-planar, the dialkyl- substituted amino and o-nitro groups being rotated out of the benzene ring. The isopropyl moiety is anti to the ortho substituent in order to minimize intra- molecular interactions. The cyclohexane ring, perpendicular to the amino group, adopts a chair * Presented in part at the XIV IUCr Congress, Perth, Australia,

Deuterium quadrupole echo NMR study of methyl group dynamics in N-Acetyl- dl-( γ- d6)-valine

2H quadrupole echo NMR was used to examine the dynamics of the two -CD 3 groups of the isopropyl moiety in N-acetyl- dl-( γ- d 6)-valine. At room temperature a Pake pattern is seen for the two groups, indicating fast limit motion, but at lower temperatures, in the range −130 to −170°C, the rates for the CD 3 groups enter the intermediate exchange regime, where the lineshapes are unique and very sensitive to the dynamic processes and geometry of the reorienting moiety. In addition, the T 1 values, the τ dependence, and the quadrupole echo intensity in the intermediate exchange region permit the spectral contributions from each group to be further separated, and thus the threefold hopping rate for each to be measured. Temperature-dependent studies yield activation energies of 15.3 and 22.2 kJ/mol for the two groups.

1H and 13C NMR conformational analysis in solution of isoproterenol a pure β‐agonist drug

Abstract13C and 1H NMR parameters were measured for isoproterenol in solution. Spin‐lattice relaxation rates were considered and C‐H and H‐H J couplings were determined. The t rotamer was shown to occur in a much greater abundance than the two g rotamers. Dynamics in solution were interpreted in terms of a nearly isotropic motion of the α‐hydroxyphenethyl moiety and of a high degree of flexibility of the isopropyl moiety, Relevant distances and dipolar connectivities were measured and used to build up a Dreiding model of the most probable conformation.

Ultrastructural, fertility, and spermicidal studies with isomers and derivatives of gossypol in male hamsters.

The effects of fourteen new, orally administered synthetic analogs of gossypol on testicular ultrastructure and fertility in hamsters and the spermicidal properties of these compounds, as well as of the optical isomers of gossypol against hamster and human sperm in vitro, are reported in this study. Test compounds were administered to adult male hamsters by daily gavage for 9 weeks at doses ranging from 15 to 50 mg/kg. The results of this study have demonstrated that the fourteen new gossypol analogs evaluated herein are not effective as male antifertility agents and their in vitro activity or lack of activity as spermicides is unrelated to their in vivo contraceptive potential. In addition, the results of the study suggest that (1) the isopropyl moiety of the gossypol molecule, like the aldehyde group, is essential for its mechanism of action and (2) the pathognomonic defect in the mitochondrial sheath induced by gossypol appears to be related to its unique activity as a male antifertility agent. The significance of these findings is discussed.

Syntheses of 8-acylamino-3,4-dihydrocarbostyril derivatives with beta-adrenergic blocking action

Twenty one kinds of 8-acylamino-5-(2-hydroxy-3-substituted aminopropoxy)-3, 4-dihydrocarbostyril derivatives were synthesized and their antagonistic activities on isoproterenol were examined. Several compounds having 3, 4-dimethoxyphenethyl or 4-carbamoylphenoxyethyl moiety in 3-substituted amino group were found to have less antagonistic activity on isoproterenol than those with tert-butyl or isopropyl moiety in 3-substituted amino group, but showed relative higher selectivity for β1-adrenoreceptors in the anesthetized dog.

Microwave, infrared and Raman spectra and structure of 2-nitropropane

The microwave spectrum of 2-nitropropane, C 3H 7NO 2, has been investigated from 12.5 to 40.0 GHz. Only α-type transitions were observed and R-branch assignments are made for the ground vibrational state. The effective rotational constants are found to have the following values: A = 5132 ± 12, B = 2895.70 ± 0.14, and C = 2706.51 ± 0.12 MHz. It is shown that these rotational constants are only consistent for the conformer where one NO bond eclipses the CH bond. From a diagnostic least-squares adjustment to fit these three rotational constants along with reasonably assumed structural parameters for the isopropyl moiety, excluding the CC distance, the following parameters are obtained: r( C C) = 1.533 ± 0.006 A ̊ , r( C N) = 1.508 ± 0.018 A ̊ , r( N O) = 1.218 ± 0.015 A ̊ , ∩ CNO = 116.8 ± 1.5°, and ∩ CCN = 108.9 ± 1.7° . From a temperature study of the microwave spectrum, it appears that the NO 2 group is nearly freely rotating. The IR (3500−80 cm −1) and Raman (3500-10 cm −1) spectra have been recorded for both the gaseous and solid phases of 2-nitropropane. The Raman spectrum of the liquid has also been recorded and qualitative depolarization values obtained. All of the normal modes are assigned based on band contours, depolarization values, and group frequencies. The vibrational data are also consistent with a nearly freely rotating NO 2 group. These results are compared to the similar quantities for several related molecules.

Nuclear magnetic resonance studies of amino acids and proteins. Side-chain mobility of methionine in the crystalline amino acid and in crystalline sperm whale (Physeter catodon) myoglobin.

We have obtained deuterium (2H) nuclear magnetic resonance (NMR) spectra and spin-lattice relaxation times (T1) of L-[epsilon-2H3]methionine, L-[epsilon-2H3]methionine in a D,L lattice, and [S-methyl-2H3]methionine in the crystalline solid state, as a function of temperature, in addition to obtaining 2H T1 and line-width results as a function of temperature on [epsilon-2H3]methionine-labeled sperm whale (Physeter catodon) myoglobins by using the method of magnetic ordering [Rothgeb, T. M., & Oldfield, E. (1981) J. Biol. Chem. 256, 1432-1446]. The results indicate that in the L-amino acid, methyl rotation having an activation energy (delta E) of 8.3 +/- 1 kJ dominates T1 at low temperatures (less than or equal to 10 degrees C), while at higher temperatures an additional large-amplitude side-chain motion occurs which causes changes in the 2H NMR line shape and T1. This motion is inhibited in the D,L lattice, indicating that lattice effects may have a strong effect on the mobility of anhydrous amino acids in the solid state. Further substitution at S delta to form the sulfonium salt [S-methyl-2H3]-methionine causes a large increase in delta E, to 15.9 +/- 2 kJ, a value comparable to the 14-16 kJ found in valine and leucine, which contain the structurally similar isopropyl moiety. These results suggest that the very low barriers to methyl rotation in the methionine side chain are due to long C-S bond lengths and the presence of only two substituents on sulfur, while the anomalous high-temperature behavior is due to a lattice-packing effect. 2H T1 results with methionine-labeled myoglobin are complex, reflecting the presence of fast large-amplitude side-chain motions, in addition to rapid methyl rotation. Our data indicate that Met-55 and Met-131 are motionally inequivalent in crystalline cyanoferrimyoglobin, in contrast to solution NMR results. We have also recorded 13C cross-polarization "magic-angle" sample-spinning NMR spectra of [epsilon-13C]methionine-labeled crystalline cyanoferrimyoglobin (at 37.7 MHz, corresponding to a magnetic field strength of 3.52 T) and of the same protein in aqueous solution. Cross-polarization transfer rates and proton rotating-frame relaxation time results again indicate that Met-55 and Met-131 are motionally inequivalent in the solid state, and the TCH data indicate that Met-55 is more solidlike. However, we find that 13C chemical shifts in solution and those in the crystalline solid state are in very close agreement, suggesting that the average solution and crystal conformations are the same, in the area of Met-55 and Met-131.

Influence of solvent and ligand-structure on the extent of intramolecular stacking interactions in mixed ligand complexes

The importance of aromatic-ring stacking for the creation of certain structural arrangements in large bio-molecules has often been emphasized ( e.g. [1]). However, the fact that at low concentrations stacking interactions between smaller molecules like amino acids and nucleotides can be promoted by the formation of a metal ion-bridge has only recently been recognized [2]. For example, the stacking between the indole moiety of tryptophanate (Trp − and the purine system of adenosine 5′-triphosphate (ATP 4−) is facilitated in ternary M(ATP)(Trp) 3− complexes [3, 4]. Similarly, the hydrophobic interaction between the isopropyl moiety of leucinate (Leu −) and the purine residue of ATP 4− is also promoted in M(ATP)(Leu) 3− complexes [4]. Based on the stability constants of the complexes and 1H-NMR shift experiments the percentage of M(A)(B) 3− cl was estimated for both types of ternary complexes: ▪ The formation of the species M(ATP)(Trp) 3− cl was first shown [5] in 1974; its occurrence was subsequently confirmed by studies in several laboratories using different methods [6]. To learn more about the factors which govern the position of the intramolecular equilibrium (1), we have now used the following simple systems, since with them structural alterations are easily achieved: ▪ In 50% aqueous dioxane (I = 0.1, 25 °C) the stacking interaction is most pronounced for n = 1; i.e. for the ternary complex Cu(Phen)(C 6H 5CH 2COO) + about 60 percent exists in the closed form. If phenylacetate is replaced by 2-(β-naphthyl)acetate the concentration of the closed isomer increases to about 80 percent. Ligands R(CH 2) nCOO − with n = 0 or n > 1 form ternary complexes with a less pronounced intramolecular stacking interaction. Variation of the solvent composition also leads to a change in the percentage of [Cu(Phen)(C 6H 5CH 2COO +] cl: solvent H 2O 30% diox. 60% diox. 90% diox. % closed isomer: 48 56 64 48 The observation of a maximal degree of formation for the closed isomer in about 60% aqueous dioxane is very surprising, because the stability of binary adducts like (Phen)(RCOO −) decreases with increasing dioxane concentration. Hence, two opposite effects must be operating in the presence of metal ions. This puzzling result is of interest for biological systems, because in these the water activity may also be altered, e.g. at the surface or in grooves of proteins. Hydrophobic interactions are important, e.g., in adduct formation between carboxypeptidase A and the inhibitor β-phenylpropionate [7]. Presently we are repeating the experiments in several ethanol/water mixtures to provide a broader generalization.

Comparative Effects of Ancymidol and Its Analogs on Growth of Peas and Ent-Kaurene Oxidation in Cell-Free Extracts of Immature Marah macrocarpus Endosperm

The plant growth retardant alpha-cyclopropyl-alpha-(4-methyoxyphenyl)-5-pyrimidine methyl alcohol (ancymidol) and a series of analogs of this substance in which one or more of the substituents were varied were tested for their comparative biological activity. The compounds were tested as inhibitors of internode elongation in peas and as inhibitors of the oxidation of ent-kaurene catalyzed by microsomal preparations from the liquid endosperm of Marah macrocarpus seeds. The relative effectiveness of a substance was generally the same as an inhibitor of the two processes. Ancymidol was the most effective. Substitution of the alcohol group of ancymidol by either methoxy or hydrogen groups reduced the activity only slightly. Substitution of the cyclopropyl group by an isopropyl moiety also had little effect on the activity. However, substitution of the cyclopropyl group with a phenyl or other aryl substituent greatly reduced the effectiveness of the analog as an inhibitor. Replacement of the 4-methoxyphenyl substituent with a similar substituent such as 4-chlorophenyl had little effect on activity, but replacement with a 2-methoxyphenyl group greatly reduced activity. Analogs in which the pyrimidyl moiety of ancymidol was modified were inactive in whole plants, but moderately active in the cell-free ent-kaurene oxidation system. The application of gibberellic acid can overcome the growth inhibitions due to treatment of the test plants with 10(-5)m or lower concentrations of the inhibitors. However, the inhibitory effects of 10(-4)m or higher concentrations of inhibitors on test plants were not overcome by the applications of exogenous gibberellic acid. These results support the idea that the effects of low concentrations of these substances on plant growth are primarily a consequence of their ability to inhibit ent-kaurene oxidation and gibberellin biosynthesis. Other modes of inhibition may operate at higher inhibitor concentrations.

Active-site determinations on forms of mammalian brain and eel acetylcholinesterase

Three forms of brain acetylcholinesterase were purified from bovine caudate-nucleus tissue and determined by calibrated gel filtration to have mol.wts. of approx. 120 000 (C), 230 000 (B) and 330 000 (A). [3H]Di-isopropyl phosphorofluoridate (isopropyl moiety labelled) was purified from commercial preparations and its concentration estimated by an enzyme-titration procedure. Brain acetylcholinesterase preparations and enzyme from eel electric tissue were allowed to react with [3H]di-isopropyl phosphorofluridate in phosphate buffer until enzyme activity was inhibited by 98%. Excess of [3H]di-isopropyl phosphorofluoridate that had not reacted was separated from the labelled enzyme protein by gel filtration, or by vacuum filtration or by extensive dialysis. The specificity of active-site labelling was confirmed by use of the enzyme reactivator, pyridine 2-aldoxime. The forms of brain acetylcholinesterase were calculted to contain approximately two (C) four (B) and six (A) active sites per molecule respectively. Acetylcholinesterase (mol.wt. 250 000) from electric-eel tissue was estimated to contain two active sites per molecule. Gradient-gel electrophoresis was used to confirm the estimation of molecular weights of brain acetylcholinesterase forms made by gel filtration. Under the conditions of electrophoresis acetylcholinesterase form A was stable, but form B was converted into a species of approx. 120 000 mol. wt. Similarly, form C of the brain enzyme was converted into a 60 000-mol.wt. form during electrophoresis. These results are in general accord with the suggestion that the multiple forms of brain acetylcholinesterase may be related to the aggregation of a single low-molecular-weight species.

ChemInform Abstract: MICROWAVE SPECTRUM, DIPOLE MOMENT AND STRUCTURE OF ISOPROPYL CYANIDE

Abstract The microwave spectrum of isopropyl cyanide, (CH 3 ) 2 CHCN, has been recorded from 26.5 to 40.0 GHz. Both A- and C-type transitions were observed. The R-branch assignments have been made for the ground and three different excited states. The following structural parameters were obtained: r (C-CN) = 1.501 A, ∠CCC = 113.8°, and an angle between the CCC plane and the CN bond of 53.8° with reasonable assumptions made for the structural parameters for the isopropyl moiety and the nitrile bond. The dipole moment components were determined to be μ a = 4.05±0.02, μ c = 1.4 ± 0.2 and μ t = 4.29 ±0.10 D. The dipole moment of t-butyl cyanide has been re-measured and found to have a value of4.34±0.04 D. From the relative intensities of the excited state lines, the two torsional modes were found to have frequencies of 200 ±20 and 249 ±10 cm −1 which gave a periodic barrier to internal rotation of 3.3 kcal mole −1 .

Microwave spectrum, dipole moment and structure of isopropyl cyanide

The microwave spectrum of isopropyl cyanide, (CH 3) 2CHCN, has been recorded from 26.5 to 40.0 GHz. Both A- and C-type transitions were observed. The R-branch assignments have been made for the ground and three different excited states. The following structural parameters were obtained: r(C-CN) = 1.501 Å, ∠CCC = 113.8°, and an angle between the CCC plane and the CN bond of 53.8° with reasonable assumptions made for the structural parameters for the isopropyl moiety and the nitrile bond. The dipole moment components were determined to be μ a = 4.05±0.02, μ c= 1.4 ± 0.2 and μ t = 4.29 ±0.10 D. The dipole moment of t-butyl cyanide has been re-measured and found to have a value of4.34±0.04 D. From the relative intensities of the excited state lines, the two torsional modes were found to have frequencies of 200 ±20 and 249 ±10 cm −1 which gave a periodic barrier to internal rotation of 3.3 kcal mole −1.

Doubling Proton Magnetic Resonance Signals by Use of Tris(dipivalomethanato)europium(III)

Doubling of some p.m.r. signals from some steroidal diastereoisomers following treatment with the shift reagent, (DPM)3Eu(III), is reported for the first time. Similar examination of the hemithioethyleneketal of methyl isopropyl ketone provided the first evidence for the diastereotopic nature of the methyl groups of the isopropyl moiety of this compound. The resolution of signals from diastereoisomers and the failure to detect the diastereotopic nature of the methylene protons of different hemithioethyleneketals is discussed briefly in terms of inhibition of free rotation in pseudocontact association.

The inhibition of activated Factor X with di: isopropyl fluorophosphate.

Summary. The esterase and coagulant activities of activated Factor X have been inhibited by radioactive di:isopropyl fluorophosphate. The amino acid sequence about the site of binding of the di:isopropyl moiety has been shown to be gly.asp.ser‐P‐gly.

Synthesis of 14C‐labelled isopropyl, diisopropyl and methyldiisopropyl amine

AbstractIsopropyl, diisopropyl and methyldiisopropyl amines, specifically labeled with 14C in the isopropyl moiety, have readily been prepared at a good yield, starting from Acetone‐2‐14C. Isopropylamine‐2‐14C [III] at 10 mC|mM was obtained by a two step synthesis with a 75% overall yield based on Acetone‐2‐14C. Diisopropylamine‐2‐14C [VI] at 3 mC|mM was prepared in a two step synthesis in 61% overall yield. From [VI], methyldiisopropylamine‐2‐14C [VII] at 1 mC|mM was obtained in one step at a 93% yield.Starting with various ketones, it is possible to carry out radiosynteses of homologous primary, secondary and tertiary amines according to the described reaction schemes.