Micellar effects upon reactions of the 2,2′,4,4′,4″-pentamethoxytrityl cation with nucleophiles

1986 ◽  
Vol 64 (6) ◽  
pp. 1179-1183 ◽  
Author(s):  
Clifford A. Bunton ◽  
Angela Cuenca
Keyword(s):  
Rate Constants ◽  
Sodium Dodecyl ◽  
Order Rate Constant ◽  
Second Order ◽  
Cetyltrimethylammonium Chloride ◽  
Micellar Effects ◽  
First Order ◽  
Order Rate ◽  
Cationic Micelles ◽  
Anionic Micelles

Cationic micelles of cetyltrimethylammonium chloride and bromide (CTACl and CTABr) speed attack of water upon the 2,2′,4,4′,4″-pentamethoxytrityl cation by a factor of ca. 5. The first-order rate constant in water is 5.51 s−1 at 25.0 °C. Anionic micelles of sodium dodecyl sulfate (SDS) have little effect on this reaction, but they strongly inhibit attack of OH−. In water, second-order rate constants for attack of OH−, CN−, and N3− are, respectively, 235, 177, and 2.8 × 105 M−1 s−1. Rate constants of reaction in CTACl go through maxima with increasing [surfactant] and analysis of the data shows that second-order rate constants at the micellar surface are similar to those in water.

scholarly journals The pH-dependence of second-order rate constants of enzyme modification may provide free-reactant pKa values

1977 ◽  
Vol 167 (3) ◽  
pp. 859-862 ◽  
Author(s):  
K Brocklehurst ◽  
H B F Dixon
Keyword(s):  
Rate Constant ◽  
Rate Constants ◽  
Ph Dependence ◽  
Order Rate Constant ◽  
Second Order ◽  
Quasi Equilibrium ◽  
Pka Values ◽  
First Order ◽  
Order Rate ◽  
Parallel Reactions

1. Reactions of enzymes with site-specific reagents may involve intermediate adsorptive complexes formed by parallel reactions in several protonic states. Accordingly, a profile of the apparent second-order rate constant for the modification reaction (Kobs., the observed rate constant under conditions where the reagent concentration is low enough for the reaction to be first-order in reagent) against pH can, in general, reflect free-reactant-state molecular pKa values only if a quasi-equilibrium condition exists around the reactive protonic state (EHR) of the adsorptive complex. 2. Usually the condition for quasi-equilibrium is expressed in terms of the rate constants around EHR: (formula: see text) i.e. k mod. less than k-2. This often cannot be assessed directly, particularly if it is not possible to determine kmod. 3. It is shown that kmod. must be much less than k-2, however, if kobs. (the pH-independent value of kobs.) less than k+2. 4. Since probable values of k+2 greater than 10(6)M-1.S-1 and since values of kobs. for many modification reactions less than 10(6)M-1.S-1, the equilibrium assumption should be valid, and kinetic study of such reactions should provide reactant-state pKa values. 5. This may not apply to catalyses, because for them the value of kcat./Km may exceed 5 X 10(5)M-1.S-1. 6. The conditions under which the formation of an intermediate complex by parallel pathways may come to quasi-equilibrium are discussed in the Appendix.

scholarly journals Compounds of 6, 13-Diamino-6, 13-Dimethyl-1, 4, 8, 11 - Tetraazacyclotetradecane

2021 ◽  
Author(s):  
◽  
Asokamali Siriwardena
Keyword(s):  
Rate Constants ◽  
Magnetic Measurements ◽  
Order Rate Constant ◽  
Acidic Solutions ◽  
First Order ◽  
Order Rate ◽  
Pendant Arm ◽  
Nickel Copper ◽  
13C Nuclear Magnetic Resonance ◽  
Kinetics Of

<p>The reaction of bis-(diaminoethane)nickel(II) chloride, ([Ni(en)2]Cl2 in methanol with formaldehyde and nitroethane in the presence of triethylamine proceeds readily to produce (6, 13-dimethyl-6, 13-dinitro-1, 4, 8, 11-tetraazacyclotetradecane)nickel(II) chloride, [Ni(dini)] - Cl2. Reduction of the nitro groups of this compound by catalytic hydrogenation yields three isomers of the pendant arm macrocyclic complex (6, 13-diamino-6, 13-dimethyl-1, 4, 8, 11-tetraazachyclotetradecane)nickel(II) chloride, designated a-, b- and c-[Ni(diam)]Cl2. These were separated by fractional crystallization. The aisomer was observed to isomerizes slowly in solution to the b- form. A parallel dissociation reaction of the a- isomer was also observed. The demetallation of a- and b- isomers of the diam complex of nickel by reaction with cyanide or concentrated acid at 140 degrees C produces the macrocycle meso-(6, 13-diamino-6, 13-dimethyl-1, 4, 8, 11-tetraazacyclotetra-decane), diam. A variety of hexamine, pentamine and tetramine complexes of diam with nickel(II), copper(II), cobalt(II) and (III), chromium(III), palladium(II), rhodium(III), zinc(II) and cadmium(II) were prepared. Hexamine and tetramine forms of labile metal complexes could be rapidly and reversibly interconverted by altering the pH. The hexamine cobalt(III) cation, [Co(diam)]3+ was by far the most inert of the prepared cobalt(III) complexes, remaining unaffected in hot acidic solutions. In contrast, a single pendant arm of the hexamine [Cr(diam)]3+ cation could be dissociated in acid. (Two possibly triamine complexes of lead were also prepared). These compounds were characterized by elemental analysis, magnetic measurements, electronic, infrared, 1H and 13C nuclear magnetic resonance spectra. The pendant arm protonation constants (log K) of diam and selected complexes of nickel, copper and palladium were calculated from potentiometric titration measurements at 25 degrees C. The log K values for diam at 25 degrees C (I = 0.1 M NaclO4) were 11.15, 9.7, 6.2 and 5.3. Kinetics of the parallel isomerization and dissociation of a-[Ni(dimH2)]4+ in HCl/NaCl solutions were monitored spectrophotometrically at 50 degrees C. The rate of reaction in acidic solutions showed a non-linear dependency on acid concentration. The observed first order rate constant (kobs) for disappearance of a-[Ni(diamH2)]4+ (by isomerization and dissociation) in 2.0 M HCl, 0.1 M NaOH and 2.0 M NaCl were 3.05 x 10-4, 2.0(3) x 10-2 and 5.0 x 10-5 s-1 respectively. The rate of the dissociation component of the reaction of a-[Ni(diamH2)]4+ in 2.0 M HCl at 50 degrees C was 1.82 x 10-7 s-1. Acid bydrolysis kinetics of (Cu[diamH2])(ClO4)4 in hydrochloric acid and perchloric acid at 50 and 70 degrees C were studied spectrophotometrically. The reactions were slow and the observed first order rate constants were to a first approximation independent of the particular acid or its concentration. The observed first order rate constants were 1 x 10-9 and 8 x 10-9 s-1 at 50 and 70 degrees C respectively. Questions about the nature of the reaction being followed have been raised.</p>

HUMAN MEIZOTHROMBIN 1, ITS ISOLATION AND PROPERTIES

1987 ◽  
Author(s):  
Zbigniew S Latallo ◽  
Craig M Jackson
Keyword(s):  
Rate Constants ◽  
Antithrombin Iii ◽  
Order Rate Constant ◽  
Red Cross ◽  
Apparent Lack ◽  
First Order ◽  
Order Rate ◽  
Matching Grant ◽  
Echis Carinatus

Meizothrombin (MT) and meizothrombin des Fragment 1 (MT1) are intermediates in the conversion of prothrombin to α-thrombin (αTH). Due to their transient character, properties of these enzymes are difficult to establish. Isolation of MT1 was achieved by affinity chromatography on D-Phe-Pro-Arginal (FPRal)immobilized on Affi-Gel 10 as originally employed for thrombin purification (Patel et al. Biochim.Biophys. Acta 748,321 (1983)). Human prethrombin 1 was activated with the purified activator from Echis carinatus venom in the presence of Ca++;, benzamidine and FPRal gel at pH 7.8. After exhaustive washing the MT1 was eluted with 0.1 M hydroxylamine in 0.15 M Na acetate buffer, pH 5.5. Under these conditions the MT1 is stable and can bestored at -70°C. Upon changing the pH of the preparation to 8.0, complete conversion into aTH occurred atroom temperature within 48 hours. Homogeneity of both preparations wasdemonstrated by PAGE. The Km and ke, values for MT1 measured on Tos-Gly-Pro-Arg pNA(0.1 M NaCl, 0.01 M TRIS, 0.01 M HEPES, 0.1% PEG, pH 7.8, 25°C) were 15.7 /iM and 126 s-1. The kinetic con stants for the aTH resulting from autocatalytic degradation of MT1 were indistinguishable from those previously established forαTH obtained by Xa activation i.e. 4.77 /μM and 126 s-1. Clotting activity of MT1 was found to be only one fifth as high as that of the resulting μTH(746 u/mg vs. 3900 u/mg as tested using the NIH standard) .Inhibitionof MTl by antithrombin III was alsomuch less rapid than αTH andmost importantly, it was not affected by high affinity heparin( Mr20,300). Under conditions of the experiment (0.3 M NaCl, 0.0rl M TRIS, 0.01 M HEPES, 2.5 mM EDTA, 0.1% PEG, pH 7.8, 25°C; [ATIII] 100 nM, [E] 10 nM), the pseudo first order rate constants in the absence of heparin were 4.04 × 10-3V1 (MTl) and 1.13 × 10-3V1 (αTH), giving apparent second order rate constants of 4.04 × 103 and 1.13 × 10-4M-1s-1. In the presence of 4.5 nM of heparin the observed first order rate constant for MTl remained unchanged whereas it increased to 6.241 × 10-3s-1 (5.5 fold) for αTH. This apparent lack of an effect of heparin may be of significance in vivo.Supported by a Matching Grant from the American National Red Cross and by the Southeastern Michigan Blood Service.

scholarly journals The reaction of Pseudomonas aeruginosa cytochrome c oxidase with carbon monoxide

1975 ◽  
Vol 151 (1) ◽  
pp. 51-59 ◽  
Author(s):  
S R Parr ◽  
M T Wilson ◽  
C Greenwood
Keyword(s):  
Cytochrome Oxidase ◽  
Flash Photolysis ◽  
Order Rate Constant ◽  
Second Order ◽  
Stopped Flow ◽  
First Order ◽  
Order Rate ◽  
Co Concentration ◽  
Pseudo First Order ◽  
Two Phases

The binding of CO to ascorbate-reduced Pseudomonas cytochrome oxidase was investigated by static-titration, stopped-flow and flash-photolytic techniques. Static-titration data indicated that the binding process was non-stoicheiometric, with a Hill number of 1.44. Stopped-flow kinetics obtained on the binding of CO to reduced Pseudomonas cytochrome oxidase were biphasic in form; the faster rate exhibited a linear dependence on CO concentration with a second-order rate constant of 2 × 10(4) M-1-s-1, whereas the slower reaction rapidly reached a pseudo-first-order rate limit at approx. 1s-1. The relative proportions of the two phases observed in stopped-flow experiments also showed a dependency on CO concentration, the slower phase increasing as the CO concentration decreased. The kinetics of CO recombination after flash-photolytic dissociation of the reduced Pseudomonas cytochrome oxidase-CO complex were also biphasic in character, both phases showing a linear pseudo-first-order rate dependence on CO concentration. The second-order rate constants were determined as 3.6 × 10(4)M-1-s-1 and 1.6 × 10(4)M-1-s-1 respectively. Again the relative proportions of the two phases varied with CO concentration, the slower phase predominating at low CO concentrations. CO dissociation from the enzyme-CO complex measured in the presence of O2 and NO indicated the presence of two rates, of the order of 0.03s-1 and 0.15s-1. When sodium dithionite was used as a reducing agent for the Pseudomonas cytochrome oxidase, the CO-combination kinetics observed by both stopped flow and flash photolysis were extremely complex and not able to be simply analysed.

Formation and spectra of flavin radicals in the presence of β-mercaptoethanol at pH 9 and 10

1984 ◽  
Vol 62 (3) ◽  
pp. 580-585 ◽  
Author(s):  
Parminder S. Surdhar ◽  
Rizwan Ahmad ◽  
David A. Armstrong
Keyword(s):  
Rate Constant ◽  
Rate Constants ◽  
Order Rate Constant ◽  
Second Order ◽  
Radical Species ◽  
Spectral Changes ◽  
Order Rate ◽  
Visible Spectra ◽  
Uv Visible ◽  
Presence And Absence

Spectral changes and rates of reaction of flavins and several radical species have been investigated at pH 7, 9, and 10 in the presence and absence of β-mercaptoethanol. The radicals •CO2−, eaq−, and [Formula: see text] reacted with FAD at pH 10 to give a spectrum of FAD •Fl− with rate constants of 7 ± 1 × 108 and 4 ± 1 × 108 M−1 s−1 for •CO2− and [Formula: see text] respectively. At pH 7 only •FlH was observed and at pH 9 a mixture of •FIH and •Fl−.Interactions between flavin radicals and sulphydryl at 10−4 M concentration did not cause perturbations in the uv–visible spectra until either the radical and/or the sulphydryl were ionized. With FAD at pH 9 or 10 and LFl at pH 10 the 370 nm peak of •Fl− was enhanced by about 15% and a second larger growth occurred near 450 nm in the presence of 10−4 to 10−2 M sulphydryl. We attribute this to the formation of labile intermediate RSHFl•−, which must also be involved in the reduction of Fl by [Formula: see text] at pH 9 or 10.The second order rate constant k13 for reaction of [Formula: see text] with FAD at pH 9 and 10 was found to be 4.2 ± 0.5 × 108 M−1 s−1 and 2.0 ± 0.4 × 108 M−1 s−1 respectively. The rate constant for the reaction between [Formula: see text] and LFl at pH 10 was slightly faster, 7 ± 1 × 108 M−1 s−1, probably reflecting the fact that LFl lacks the bulky negatively charged adenine dinucleotide group of FAD.

On the Interaction Between Human Plasma Kallikrein and C1-Esterase Inhibitor

1983 ◽  
Vol 49 (03) ◽  
pp. 193-195 ◽  
Author(s):  
Torbjörn Nilsson
Keyword(s):  
Dissociation Constant ◽  
Human Plasma ◽  
Rate Constant ◽  
Enzyme Inhibitor ◽  
Order Rate Constant ◽  
Second Order ◽  
Plasma Kallikrein ◽  
First Order ◽  
Order Rate ◽  
Esterase Inhibitor

SummaryThe kinetics of the reaction between human plasma kallikrein and CĪ-esterase inhibitor was studied in a purified system. By monitoring the inhibition reaction for extended periods of time, it was found to proceed in two consecutive steps, a fast reversible second-order binding step followed by a slower, irreversible first-order transition. The rate constants in this reaction model were determined, as well as the dissociation constant of the initial, reversible enzyme-inhibitor complex. Thus, at 37° C the second-order rate constant was found to be 5 · 104 M -1 · s-1, the first order rate constant was 5 · 10-4 s-1 and the dissociation constant K was 1.5 · 10-8 M. Heparin (28 U/ml) and 6-aminohexanoic acid (10 mM) had no effect on the k1 of the of the reaction.

Structural and Functional Investigations of Active Site Binding Regions in Factor VIIa.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2029-2029
Author(s):  
S. Paul Bajaj ◽  
Amanda Sutton ◽  
Sreejesh Shanker ◽  
Amy E Schmidt ◽  
Sayeh Agah ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Rate Constant ◽  
Active Site ◽  
Rate Constants ◽  
Site Occupancy ◽  
Order Rate Constant ◽  
Second Order ◽  
Factor Vii ◽  
Protease Domain ◽  
Order Rate

Abstract Factor VII (FVII) consists of an N-terminal γ-carboxyglutamic acid (Gla) domain followed by two epidermal growth factor-like (EGF1 and EGF2) domains and the C-terminal protease domain. Activation of FVII results in a two-chain FVIIa molecule consisting of a light chain (Gla-EGF1-EGF2 domains) and a heavy chain (protease domain) held together by a single disulfide bond. The complex of tissue factor (TF) and FVIIa activates FIX and FX during coagulation. FVIIa on its own is structurally more “zymogen-like” and when bound to TF it is more “active enzyme-like.” We obtained crystal structures of EGR-VIIa/soluble (s) TF (2.9 Å resolution), dansyl-EGR-VIIa/sTF (1.9 Å resolution) and benzamidine-VIIa/sTF (1.6 Å resolution). We also investigated the effect of TF binding on the S1, S2, and S3/S4 subsites (Schechter and Berger, BBRC, 27:157-162, 1967) in FVIIa. The affinity of variously inhibited FVIIa to sTF was also measured using Biacore technology. For obtaining second order inhibition rate constants, FVIIa ± soluble (s) TF was incubated with each inhibitor for various times, diluted several fold and assayed for the residual FVIIa activity. The second order rate constants were obtained by plotting the first order rate constants versus the inhibitor concentrations. These data are summarized in the table below. From these data it appears that all subsites are affected upon FVIIa binding to sTF. Since in the crystal structure of EGR-VIIa/sTF the P1 Arg residue is the only residue that makes contact with FVIIa, it follows that the S1 site is affected ~10-fold upon binding to sTF. Adding a dansyl group that partially occupies the S3/S4 position (1.9 Å structure) increases the second order rate constant 7-fold (2.41 versus 0.35) over that of EGR-ck. Moreover the addition of Pro (DFPR-ck) or Phe (DFFR-ck) residue occupying the S2 position increases the second order rate constant 357-fold and 1500- fold, respectively (125 and 525 versus 0.35). Thus, comparison of dEGR, DFPR, DFFR inhibition suggests that FVIIa prefers Phe at S2 and at S3/S4 positions, and that TF opens up the S1/S2/S3/S4 sites for substrate or inhibitor occupancy. These data are consistent with LTR (P3/P2/P1) residues in FX at its activation cleavage site as well as with LTR (P3/P2/P1) residues and FTR (P3/P2/P1) residues at the 145-146 and 180-181 FIX activation cleavage sites, respectively. Thus, these studies with chloromethylketone inhibitors have biologic relevance. For Biacore studies, sTF was amine coupled to a CM5 chip. The binding of unoccupied active site FVIIa in 5 mM calcium to sTF was characterized by a KD of 7 nM. Benzamidine (10 mM)-VIIa, p-aminobenzamidine (pAB, 1 mM)-VIIa, EGR-VIIa, dEGR-VIIa, DFPR-VIIa and DFFR-VIIa each bound to sTF with KD values ranging from 1- 2 nM. These affinity measurements indicate that the S1 site occupied FVIIa molecule (benzamidine-FVIIa, pAB-VIIa) has essentially the same conformation as the S1/S2/S3/S4 occupied FVIIa. This conclusion is consistent with similar crystal structures of variously inhibited FVIIa molecules complexed with sTF. The differential rates of incorporation of various chloromethylketone inhibitors could be due to the interaction of various residues (P1, P2, P3, P4) with the corresponding active subsites (S1/S2/S3/S4) of FVIIa. Additionally, the rate of incorporation of chloromethylketone inhibitors into FVIIa also involves the irreversible alkylation step, which could be faster for DFFR-ck and DFPR-ck. Once these inhibitors are incorporated, it appears that they induce the same conformation in FVIIa as achieved by S1 site occupancy alone. Thus S1 site occupancy in FVIIa induces the required conformation to modestly increase the affinity for TF. Second Order Rate Constants for Inhibition of FVIIa ± sTF with Various Chloromethylketone (ck) Inhibitors Inhibitor Minus sTF k (min−1 mM−1) Plus sTF k (min−1 mM−1) Fold Difference EGR-ck 0.04 0.35 8.8 dansyl EGR-ck 0.07 2.41 34.4 (D)FPR-ck 2.3 125 54.3 D)FFR-ck 5.6 525 93.8

Pyrimidine reactions. XI. Amination rates for two chlorodimethylprimidines without solvent

1965 ◽  
Vol 18 (11) ◽  
pp. 1811 ◽  
Author(s):  
DJ Brown ◽  
JM Lyall
Keyword(s):  
Rate Constants ◽  
Second Order ◽  
Arrhenius Parameters ◽  
First Order ◽  
Order Rate

Second-order rate constants, Arrhenius parameters, and isokinetic temperatures are presented for the reactions of 2-chloro-4,6-dimethylpyrimidine and 4-chloro-2,6-dimethylpyrimidine with some n-alkyl-, branched alkyl-, and dialkylamines in the absence of a solvent. The differences between these values and those available for the same reactions in a solvent are briefly discussed. An equation is derived for satisfactorily converting the apparent first-order rate constants previously reported by us into second-order rate constants.

Reversible ring opening in the hydrolysis of spiro ortho esters

1985 ◽  
Vol 63 (10) ◽  
pp. 2673-2678 ◽  
Author(s):  
Robert A. McClelland ◽  
Claude Moreau
Keyword(s):  
Rate Constant ◽  
Rate Constants ◽  
Ring Opening ◽  
Lone Pair ◽  
Order Rate Constant ◽  
Product Analysis ◽  
Ortho Ester ◽  
First Order ◽  
Order Rate ◽  
Ortho Esters

Hydrolysis kinetics are reported for four spiro ortho esters: 3,4-dihydro-6-methoxy-1H-2-benzopyran-1-spiro-2′-1′,3′-dioxolane (13), its 1′,3′-dioxane analog (14), and the 6-unsubstituted versions of each (11 and 12). For comparison, also included are the diethoxy analogs: 1,1-diethoxy-3,4-dihydro-6-methoxy-1H-2-benzopyran (10) and the 6-unsubstituted compound (9). Product analysis implicates an initial opening of the dioxolane or dioxane ring in the spiro ortho esters, as expected on the basis of stereoelectronic considerations. The intermediate dialkoxycarbocations can be observed in HCl solutions. A detailed analysis has been carried out for the 6-methoxy systems to provide the rate constants k1, the second-order rate constant for H+-catalyzed formation of the cation from the ortho ester, k2, the first-order rate constant for water addition to the cation, and k−1, the first-order rate constant for ring closing of the cation to reform the ortho ester. The two spiro ortho esters are shown in this analysis to undergo reversible ring opening in their hydrolysis, in that values of k−1, are greater than k2. The differences, however, are not large, k−1/k2 being 1.2 (dioxolane, 13) and 3.8 (dioxane, 14). Comparison with the diethoxy ortho ester also reveals that the ring opening process (k1, rate constants) is inherently more difficult with the dioxolane, although not with the dioxane. An argument involving lone pair orientation is advanced to explain this.

Elucidation of the Nucleophilic Potential of Diazocyclopentadiene

Synthesis ◽  
2022 ◽  
Author(s):  
Herbert Mayr ◽  
Manfred Hartnagel ◽  
Armin R. Ofial
Keyword(s):  
Rate Constants ◽  
Second Order ◽  
Order Conditions ◽  
First Order ◽  
Electrophilic Substitutions ◽  
Order Rate ◽  
Nucleophilic Reactivity ◽  
Pseudo First Order

AbstractDiazocyclopentadiene reacts with benzhydrylium ions (Ar2CH+) to give 2,5-dibenzhydryl-substituted diazocyclopentadienes. The kinetics have been determined photometrically in dichloromethane under pseudo-first-order conditions using diazocyclopentadiene in excess. Plots of the second-order rate constants (log k 2) versus the electrophilicity parameters E of the benzhydrylium ions gave the nucleo­philicity parameter N = 4.84 and susceptibility s N = 1.06 for diazo­cyclopentadiene according to the correlation log k(20 °C) = s N(E + N). Diazocyclopentadiene thus has a similar nucleophilic reactivity as pyrrole. Previously reported electrophilic substitutions of diazocyclopentadiene are rationalized by these parameters and new reaction possibilities are predicted.

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