Log Mw Research Articles

The in vivo degradation, absorption and excretion of PCL-based implant

The in vivo degradation of poly ( ε-caprolactone)(PCL) was observed for 3 years in rats. The distribution, absorption and excretion of PCL were traced in rats by radioactive labeling. The results showed that PCL capsules with initial molecular weight (Mw) of 66 000 remained intact in shape during 2-year implantation. It broke into low molecular weight (Mw=8000) pieces at the end of 30 months. The Mw of PCL deceased with time and followed a linear relationship between log Mw and time. Tritium-labeled PCL (Mw 3000) was subcutaneous implanted in rats to investigate its absorption and excretion. The radioactive tracer was first detected in plasma 15 days after implantation. At the same time radioactive excreta was recovered from feces and urine. An accumulative 92% of the implanted radioactive tracer was excreted from feces and urine by 135 days after implantation. In the mean while, the plasma radioactivity dropped to the background level. Radioactivity in the organs was all close to the background level confirming that the material did not cumulate in body tissue and could be completely excreted.

Melt rheology of variableL-content poly(lactic acid)

Polylactides (PLAs) have been known for several decades and have recently gained considerable commercial significance. This development makes it highly desirable to have the rheological properties of these materials well characterized and reduced to useable mathematical models. However, comprehensive rheological characterization of PLAs is not yet available from the literature. In this study, rheological and thermal measurements were made on a comprehensive and well-characterized set of homopolymers and copolymers spanning wide ranges of molecular mass and stereoisomer proportions (L content). For all compositions within the weight average molecular weight range of 105–106(g∕mol) and a reference temperature of 180 °C, the zero shear viscosity is described by the relationship log(η0)=−14.26+3.4log(Mw), the plateau modulus is 1.0±0.2MPa, and average WLF parameters are c1=3.241∕K and c2=164.9K; the later correspond to a Vogel temperature of 288.25 K. The values of the glass transition temperatures at infinit...

Mechanistic Roles of Ser-114, Tyr-155, and Lys-159 in 3α-Hydroxysteroid Dehydrogenase/Carbonyl Reductase from Comamonas testosteroni

3alpha-hydroxysteroid dehydrogenase/carbonyl reductase (3alpha-HSD/CR) from Comamonas testosteroni, a short chain dehydrogenase/reductase, catalyzes the oxidation of androsterone with NAD+ to form androstanedione and NADH. A catalytic triad of Ser-114, Tyr-155, and Lys-159 in 3alpha-HSD/CR has been proposed based on structural analysis and sequence alignment of the short chain dehydrogenase/reductase family. The 3alpha-HSD/CR-catalyzed reaction has not been kinetically analyzed in detail, however. In this study, we combined steady-state kinetics, site-directed mutagenesis, and pH profile to explore the function of Ser-114, Tyr-155, and Lys-159 in 3alpha-HSD/CR-catalyzed reaction. The catalytic efficiency of wild-type and mutants S114A, Y155F, K159A, and Y155F/K159A is 4.3 x 10(7), 7.3 x 10(4), 1.7 x 10(4), 2.4 x 10(5), and 71 m(-1)s(-1), respectively. The values of pKa on kcat/Km for the wild-type, S114A, Y155F, K159A, and Y155F/K159A are 7.2, 7.4, 8.4, 9.1, and 10.2, respectively. Mutant S114A/Y155F exhibits a pH-independent profile with 10(-5) times of wild-type activity at pH 10.5. The activity decreases as the pH lowers, which indicates that a functional group with an apparent pKa of 7.2 is involved in the general base catalysis for wild-type 3alpha-HSD/CR. The pKa shift to 9.1 for mutant K159A suggests the role of Lys-159 is to lower the pKa of the residues involved in the general base catalysis. Because pH dependence is observed for both S114A and Y155F mutants and pH independence is observed in S114A/Y155F, Tyr-155 may be important as a general base catalysis in the wild-type, whereas Ser-114 may act as a general base on mutant Y155F to catalyze the reaction.

Anticancer agents: tumor cell growth inhibitory activity and binary QSAR analysis.

The tumor cell growth inhibitory activities (log 1/GI(50)) of 166 anticancer agents studied at the National Cancer Institute (NCI) in vitro anticancer screening program have allowed us to analyze the relative importance of physicochemical parameters in influencing the inhibitory activities. Increased molecular weight, as measured by the logarithm of molecular weight (log MW), is found to be an important contributor to the tumor cell growth inhibitory activities. The tumor cell growth inhibitory activities in different subpanels of the tumor cells are highly inter-correlated with each other. A simple binary quantitative structure-activity relationship (QSAR) model was derived from the 166 anticancer drugs, based on the tumor cell growth inhibitory activities transformed into a binary (active or inactive) data format. The model obtained can be tested with additional new data, and may be useful to identify active compounds from a large compound library to be included in high throughput screening.

Structure-activity relationship: analyses of p-glycoprotein substrates and inhibitors.

A large number of structurally and functionally diverse compounds act as substrates or modulators of p-glycoprotein (p-gp). Some of them possess multiple drug resistance (MDR)-reversing activity, but only a small number of them have entered clinical study. In order to uncover the factors which exert a significant impact on the interaction between substrates/modulators and p-gp, we have performed structure-activity relationship (SAR) analyses, including molecular modelling, two-dimensional (2D) and three-dimensional (3D) parameter-frame-setting analysis, quantitative structure activity relationship (QSAR) analysis among substrates/modulators, as well as clinically promising MDR-reversing agents. The physicochemical parameters C log P, CMR and all regression equations were derived by using C log P version 4.0 and the latest CQSAR software, respectively. Molecular modelling and all other parameter calculations were performed by using HyperChem version 5.0 program, after geometry optimization and energy minimization using the AM1 semiempirical method. SAR analyses indicate that MDR reversal activity is correlated with the lipophilicity (C log P), molecular weight (log Mw), longest chain (Nlc) of the molecule and the energy of the highest occupied orbital (Ehomo). In addition, the presence of a basic tertiary nitrogen atom in the structure is also an important contributor to p-gp inhibitory activity. Some separation in space is achieved for different subsets of p-gp substrates and inhibitors using Nlc, C log P and Ehomo as three independent parameters in the 3D-parameter-frame setting. A highly effective p-gp modulator candidate should possess a log P value of 2.92 or higher, 18-atom-long or longer molecular axis, and a high Ehomo value, as well as at least one tertiary basic nitrogen atom. The results obtained may be useful in explaining drug-p-gp interactions for different compounds, including drug interactions and the development of new MDR chemosensitizers.

Effect of 1- O-ethyl-3-butylcyclohexanol on the skin permeation of drugs with different physicochemical characteristics

The effects of 1- O-ethyl-3-butylcyclohexanol (OEBC) on the in vitro skin permeation of ten model drugs with different physicochemical properties across excised rat skin were evaluated. The results showed that the addition of OEBC significantly improved the in vitro skin permeation of the model drugs compared with the control (without OEBC). To clarify the promoting mechanism of OEBC, a multiple regression analysis was employed. When the permeation study was performed without OEBC, the permeability coefficient was quantitatively predicted as a linear function of molecular weight (log MW) and their lipophilicity (partition coefficient of drugs between octanol and water (log K o/w)) with a sufficiently high correlation coefficient ( r=0.842). It was suggested that skin permeation of drugs without OEBC was explained as a function of diffusion of drugs through the skin and partitioning of drugs to the skin. Although OEBC was administered, the permeability coefficient of drugs cannot be predicted as a linear function of log MW and log K o/w ( r=0.572).

Separation and Characterization of Barley Starch Polymers by a Flow Field‐Flow Fractionation Technique in Combination with Multiangle Light Scattering and Differential Refractive Index Detection

ABSTRACTFlow field‐flow fractionation (flow FFF) with frit inlet and frit outlet mode (FIFO) was coupled online to multiangle light scattering (MALS) and refractive index (RI) detectors to investigate the molecular characteristics of normal and zero amylose barley starch polymers. Application of two different cross‐flows, 0.35 mL/min followed by 0.1 mL/min, and constant channel and frit flows of 0.1 and 1.0 mL/min, respectively, permitted a complete separation of amylose and amylopectin. The improved signals from the detectors due to application of the FIFO mode enabled the proper characterization of the small molecular weight species, as well as significantly enhanced the reproducibility of the measurements. The weight‐average molecular weight (Mw) and zaverage root‐mean‐square (RMS) radii of gyration (Rg) values for amylose and amylopectin in the normal starch samples were 2.3 × 106 and 280 × 106, and 107 and 260 nm, respectively. The Mw and Rg of amylopectin in the zero amylose starch samples were 360 × 106 and 267 nm, respectively. The slopes (α) obtained by plotting log Mw versus log Rg for amylose and amylopectin were 0.6 and 0.3, respectively. These results are in good agreement with the theoretical prediction of the molecular conformation of amylose and amylopectin.

Radius of Gyration of Polystyrene Combs and Centipedes in Solution

The method of Iatrou et al. (Macromolecules 1998, 31, 6697) was applied to synthesize a normal comb polystyrene sample with uniform side chains equally spaced along the main chain but with the most probable distribution in the main chain length. The molecular weights of the side chain and the connector (the part of the main chain between the neighboring side chains) were 3.5 × 104 and 2.3 × 104, respectively. The sample was analyzed using a gel-permeation chromatography system with a multiangle light scattering and refractive index detector to determine the relationship between the z-average mean square radius of gyration 〈S2〉 and the weight-average molecular weight Mw. Tetrahydrofuran (THF) was chosen as the solvent. The relation fell considerably below that for linear polystyrene. The slope of the plot of log 〈S2〉1/2 vs log Mw for the comb polymer was 0.46, a value much smaller than the Flory exponent 0.6 for linear chains in good solvents. Similar measurements were also made on polystyrene centipedes prepared by Iatrou et al., which have two side chains at each junction point. As the ratio r of the molecular weight of the side chain to that of the connector increased, the 〈S2〉 vs Mw relation was lowered. Comparison of the experimental relationship with theoretical predictions for flexible discrete chains suggested that the main chains of the two types of polymer are stiffened by the crowding of the side chains. To estimate the backbone stiffness, 〈S2〉 was calculated on the basis of the wormlike comb model whose main and side chains have different Kuhn lengths λ-1 and λs-1, respectively. With λs-1 = 2 nm and the linear mass density = 390 nm-1 (for both main chain and side chains), λ-1 was estimated so as to give the closest agreement between the calculated and measured 〈S2〉. It was found that the calculated values for the comb polymer with λ-1 = 5.5 nm agree closely with the experimental data. The data for the centipedes were also explained by the theory, which showed the backbone stiffness to increase with increasing r.

Caco-2 cell permeability vs human gastrointestinal absorption: QSPR analysis.

The aim of this study is to elucidate quantitative structure-permeability relationship (QSPR) of various organic molecules through Caco-2 cells, and to ascertain the relationship between gastrointestinal (GI) absorption in humans and Caco-2 cell permeability. Caco-2 cell permeability and human GI absorption data were obtained from the literature. The maximum hydrogen bond-forming capacity corrected for intra-molecular H-bonding (Hbc) and Lien's QSAR model were used in this study. The latest CQSAR software was utilized in calculating the logarithm of partition coefficient in octanol/water (Clog P) and in deriving all regression equations. For 51 compounds, a significant correlation was obtained between Caco-2 cell permeability (log Pcaco-2) and Hbc, octanol/PBS (phosphate buffered saline, pH 7.4) distribution coefficient (log Doct), log MW and an indicator variable (I) for the charge, with a correlation coefficient of 0.797. When these compounds were divided into three subgroups, namely neutral, cationic and anionic compounds, much better correlations (r = 0.968, 0.915 and 0.931, respectively) were obtained using different combinations of various physico-chemical parameters. A plot of human GI absorption vs. Caco-2 cell permeability obtained from different laboratories reveals that Caco-2 cell permeability cannot be used to precisely predict human GI absorption for compounds with Pcaco-2 below 5 x 10(-6) cm/s, due to interlaboratory and experimental variabilities, and the lack of a simple correlation between human GI absorption and Caco-2 cell permeability. Caco-2 cell permeability may be estimated from the structures of drug molecules using the above-mentioned physicochemical parameters. In general, for compounds with Pcaco-2 above 5 x 10(-6) cm/s, human GI absorption ranges from 50 to 100%. This is generally acceptable for development into oral dosage form. For the compounds with Pcaco-2 below 5 x 10(-6) cm/s, careful interpretation of caco-2 cell permeability and use of internal standard for comparison are recommended. Otherwise, good drug candidates may be excluded due to incorrectly predicted poor absorption.

Effects of ionic strength and pH on the diffusion coefficients and conformation of chitosans molecule in solution

The effects of ionic strength and pH on the diffusion coefficients and gross conformation of chitosan molecules in solution were studied. Chitosan with 83% degree of deacetylation (DD) was prepared from red shrimp (Solemocera prominenitis) processing waste. Ten different molecular weight chitosans were prepared by ultrasonic degradation, and their molecular weights were determined by static light scattering. The weight-average molecular weight (Mw) were between 78 to 914 kilo dalton (KDa). Solution of different ionic strengths (I = 0.01, 0.10, and 0.20) but the same pH (2.18) and different pHs (2.37, 3.10, and 4.14) but the same ionic strength (I = 0.05) were prepared to measure their mutual diffusion coefficient (Dm). The diffusion coefficients for standard condition (D20,w) were derived from Dm. Intrinsic viscosities ([η]) were determined by a capillary viscometer in different pH solutions. The Mark–Houwink exponents a and ε were obtained from plots of Log [η] and Log D20,w versus Log Mw, respectively. The results show that diffusion coefficients increased with increasing ionic strength or with increasing pH or with decreasing Mw. Value of ε and a were between 0.503 to 0.571 and ranged from 0.543 to 0.632, respectively. The results indicates that chitosans conformation were in random coil in solutions in the ranges of ionic strength and pH studied. The values of a*, ε* and a**, ε**, Mark–Houwink exponents of smaller and higher than 223 KDa chitosans, respectively, were between 0.752 to 0.988 and 0.585 to 0.777 for smaller Mw chitosans and 0.406 to 0.428 and 0.430 to 0.518 for larger Mw chitosans, respectively. Molecular-weight-induced conformational transition occurred because smaller Mw chitosans was more extended than higher Mw chitosans. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 73: 2041–2050, 1999

Molecular weight determination of 83% degree of decetylation chitosan with non-Gaussian and wide range distribution by high-performance size exclusion chromatography and capillary viscometry

Molecular weight determination of 83% degree of deacetylation (DD) chitosan with non-Gaussian and broad molecular weight distribution by high-performance size exclusion chromatography (HPSEC) and by capillary viscometry were proposed. The relationships between weight average retention volumes (RVw) of HPSEC and intrinsic viscosities ([η]) measured by capillary viscometer and the weight average molecular weight (Mw) measured by static light scattering were established for routine molecular weight determination of chitosans either by HPSEC or by the capillary viscometry method, respectively. These results showed: relationships of RVw and Mw for different Mw of 83.0% DD chitosans can be expressed by the equation Log Mw = −0.433 RVw + 11.66. The RVw of other DD chitosans do not correlate well with this equation. It indicated that DD of chitosan affected the relationship of RVw and Mw of chitosans studied. The Mark–Houwink constant a decreased from 0.715 to 0.521, as the solution ionic strength increased from 0.01M to 0.30M, whereas constant k increased from 5.48 × 10−4 to 2.04 × 10−3 over the same range of ionic strength solutions. The established RVw and Mw equation and [η] and Mw equation (Mark–Houwink equation) can be routinely used to determine the molecular weight from RVw or [η] of chitosan by HPSEC or by capillary viscometer, respectively, without the need of expensive instrumentation. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 1905–1913, 1999

Epidermal iontophoresis: II. Application of the ionic mobility-pore model to the transport of local anesthetics.

An in vitro study was carried out to determine the iontophoretic permeability of local anesthetics through human epidermis. The relationship between physicochemical structure and the permeability of these solutes was then examined using an ionic mobility-pore model developed to define quantitative relationships. The iontophoretic permeability of both ester-type anesthetics (procaine, butacaine, tetracaine) and amide-type anesthetics (prilocaine, mepivacaine, lidocaine, bupivacaine, etidocaine, cinchocaine) were determined through excised human epidermis over 2 hrs using a constant d.c. current and Ag/AgCl electrodes. Individual ion mobilities were determined from conductivity measurements in aqueous solutions. Multiple stepwise regression was applied to interrelate the iontophoretic permeability of the solutes with their physical properties to examine the appropriateness of the ionic mobility-pore model and to determine the best predictor of iontophoretic permeability of the local anesthetics. The logarithm of the iontophoretic permeability coefficient (log PC(j,iont)) for local anesthetics was directly related to the log ionic mobility and MW for the free volume form of the model when other conditions are held constant. Multiple linear regressions confirmed that log PC(j,iont) was best defined by ionic mobility (and its determinants: conductivity, pKa and MW) and MW. Our results suggest that of the properties studied, the best predictors of iontophoretic transport of local anesthetics are ionic mobility (or pKa) and molecular size. These predictions are consistent with the ionic mobility pore model determined by the mobility of ions in the aqueous solution, the total current, epidermal permselectivity and other factors as defined by the model.

Correlation of physiochemical parameters to the hydrophobic contribution constants of amino acid residues in small peptides.

This paper attempts to correlate the hydrophobic contribution constants (faa) of 21 amino acids in small peptides with commonly used physiochemical parameters. These faa constants can then be used to predict hydrophobicity change in peptides when any one of the amino acid residue is substituted with another. Non-weighted least squares method was used in deriving regression equations with a BMDP program. A Hyperchem program for Windows was used to calculate the group dipole moments of the side chain. A good correlation (r = 0.97) was obtained using a four parameter equation including molecular weight (log MW), hydrogen bond forming ability (HB), dipole moment (mu) and an indicator variable (I) to account for the presence of a free primary amine group in the side chain. This proposed model should be useful in predicting the hydrophobic contribution constants of other uncommon amino acids and in the estimation of log P'values of numerous peptides containing different possible combinations of these amino acids, as well as log P' values resulting from amino acid substitution as is done in site-directed mutagenesis.

Hydrophobicity of oligopeptides having un-ionizable side chains.

The hydrophobicity of any peptide is a physicochemical property not only of the amino acid sequence, but also of the secondary and tertiary structure. It is also an essential factor to consider in peptide drug delivery, which has become increasingly important in recent years with the discovery of many peptides with potential pharmaceutical uses. The hydrophobicities (log P) of dito pentapeptides reported by Akamatsu and Fujita have been correlated with 12 parameters including 7 indicator variables. We have tried to simply this equation by using more common and simple parameters. Good correlations have been obtained for log P with a five-parameter equation using the sum of the hydrophobicity of component amino acids (log Paa), molecular weight (log MW), the frequency of beta-turn formation (F beta) of peptides, which is an important tertiary structural parameter, the dipole moment (mu) calculated with a computer-assisted program, and the number of amino acids in a peptide (N). This equation should be useful in drug delivery in predicting the relative hydrophobicity of new peptides with no ionizable side chains.

Physicochemical properties of agrochemicals: Their effects on foliar penetration

AbstractUptake and translocation of 26 chemicals (herbicides, fungicides, growth regulators, insecticides and model compounds), formulated with and without ‘Ethylan TU’ (NP8) surfactant, have been determined 24, 48 and 72 h after spraying onto leaves of maize, rape, strawberry and sugar beet. Eight of the chemicals may be classified as polar (log partition coefficient (P) < 0) and 18 as lipophilic (log P 0·8‐4·6). Chemicals penetrated more readily into waxy leaves of rape and strawberry than into less‐waxy sugar beet, whilst lowest rates were observed for maize. Rates of uptake varied from exceedingly low (< 2% 72 h after application) for uracil, maleic hydrazide, isoproturon and methyl phenylurea applied to maize, to rapid (>98% within 24 h of application) for acephate and triadimefon applied to strawberry leaves. The effects of NP8 on rates of chemical uptake were classified into 4 types, viz:‐ low rates, with limited enhancement by NP8; high rates unaffected by NP8; marked enhancement by NP8 within 24 h; and continuous enhancement by NP8 over 0‐72 h. Translocation into the tissues immediately adjacent to the target site was greater for waxy than less‐waxy plants, enhancement by NP8 was attributed to its effects on penetration rather than to surfactant interactions at the sub‐cuticular level. Logarithms of physicochemical properties (partition coefficient, water solubility S, molecular weight MW), together with deposit area and melting point (m.p.) values were used to investigate relationships with uptake and translocation. In most cases the variability could not be described adequately in a simple linear form. Regressions using the entire group of 26 chemicals also showed poor correlations between uptake patterns and individual variables. Polynomials in log S, log P, log MW and m.p. were used to test for complex relationships. A quadratic polynomial in log P, log S and m.p. accounted for slightly more (77%) of the variability between the means for total uptake than a cubic polynomial in log P and log S (75%). Although both regressions were significant, the ‘lack of fit’ indicated that other factors need to be included to account fully for the variability in rates of uptake and translocation.

Analysis of the quantitative structure activity relationship of technetium-99m-labeled diaminedithiol (DADT) and propyleneamineoxime (PAO) brain blood flow analogues

In the search for new brain imaging agents for the use with single photon emission computed tomography (SPECT), quantitative structure activity relationship (QSAR) analysis of the correlations between initial brain uptake and physicochemical parameters like lipophilicity, log P, molecular weight, log MW and log U D (undissociated/dissociated), of the 99mTc-DADT (diaminedithiol) complexes and 99mTc-PAO (propyleneamineoxime) complexes have been analyzed. High correlations are found for both the 99mTc-DADT complexes ( r = 0.94) and for the 99mTc-PAO complexes ( r = 0.83) which are significant at 99.9 and 99.5 percentile level, respectively. These results will help the further design of better ligands for 99mTc in brain imaging.

Solute Structure-Permeability Relationships in Human Stratum Corneum

The permeability coefficients (kp) of a series of methyl-substituted p-cresols were determined in human stratum corneum along with their partition coefficients (PC) between water and untreated stratum corneum, delipidized stratum corneum, octanol, and heptane. The PC values were identical in untreated and delipidized stratum corneum, suggesting that the stratum corneum/water PC data reflect the protein domain rather than the lipids. Although uptake into human stratum corneum was relatively insensitive to solute lipophilicity, reflecting the predominant role of proteins in the uptake, permeability coefficients were found to be more sensitive to lipophilicity, suggesting that transport is by a lipid pathway. A log-log plot of kp versus stratum corneum/water PC within the phenol series is linear, but with a slope of 3.6, indicating that kp is not directly proportional to PC. Functional group contributions to the free energy of the transfer process reflected in permeability or partitioning experiments were compared with group contribution data generated previously for the same substituents attached to the chain terminus of 21-esters of hydrocortisone. Within experimental error, a given functional group altered permeability by the same factor in either series of compounds. Group contributions of polar, hydrogen bonding substituents obtained from kp data were similar to those from octanol/water PC data, suggesting that the barrier microenvironment resembles that of a hydrogen bonding organic solvent. Comparison of the kp values of substituted p-cresols with those of hydrocortisone esters having similar lipophilicities also indicated a steep dependence of kp on molecular weight (log kp = constant + psi log PC - n log MW, n = 4.6) similar to the dependence observed in other biomembranes and isolated lipid bilayers.

Calibration of the relative molecular mass of proteoglycan subunit by column chromatography on Sepharose CL-2B.

Calibration relationships were derived for cartilage proteoglycan subunit (PGS) that relate the inverse z-average hydrodynamic radius (Rs) and the weight-average Mr (Mw) to the partition coefficient (Kav.) for PGS when chromatographed on a Sepharose CL-2B column. PGS isolated from chick limb-bud chondrocyte cell cultures was fractionated chromatographically into eight pools, for which Mw and Rs were determined by total-intensity and dynamic light-scattering measurements. These data were found to be related to Kav. through the following empirical equations: log Mw = -(1.65 +/- 0.27)Kav. +(6.58 +/- 0.08); log Rs = -(0.69 +/- 0.04)Kav. +(2.75 +/- 0.01). Application of these relationships to the chromatographic data led to Mw = 1.48 X 10(6) and Rs = 38.7 nm (387 A) for the unfractionated specimens compared with values of Mw = 1.46 X 10(6) and Rs = 38.2 nm (382 A) determined by light-scattering. Our results were found to be consistent with previously proposed phenomenological models for the gel-filtration mechanism. Application of these calibration relationships to Kav. for several unfractionated specimens led to predicted values of Mw and Rs that are accurate to within 10%.

Static and dynamic light scattering from dilute insulin solutions.

AbstractStatic and dynamic light‐scattering measurements are reported on zinc‐insulin at room temperature (21 ± l°C) and pH = 6.88 in 0.1M NaCl aqueous solution. The experiments were performed at very low concentration, in the range 0.12 × 10−4 to 0.90 × 10−4 g cm−3. Within experimental error, we find no evidence for a critical micellar concentration in this system. The aggregation phenomenon starts immediately after preparation of the solutions, and takes several days to come to stable equilibrium. The concentration dependence of the diffusion coefficients, Dz, = Do (1 — kDC), is negative, and kD was observed to decrease as a function of time, while the aggregate size was found to increase. The equivalent concentration coefficient, −2BMW, obtained from static light scattering, showed a similar behavior, and, within experimental error, was found to be numerically equal to kD. From the relation found between the diffusion coefficient at infinite dilution and the molecular weight of the aggregates, log D0 = −0.240 log Mw − 5.077, we deduce that the insulin aggregates are compact structures with a characteristic radius of 0.71 Å/(dalton)1/3, surrounded by a hydration layer of a thickness of 8.0 Å. The equilibrium aggregation number is approximately 10.

Solution properties and branching of styrene‐butadiene rubber

AbstractA number of polydisperse samples of styrene‐butadiene rubber differing in the preparation conditions were investigated by the methods of light scattering, viscometry and sedimentation analysis. The molar masses were measured by light scattering in cyclohexane solutions (25°C, thermodynamically good solvent) and by the Archibald approach to equilibrium method in methyl‐n‐propyl ketone (21°C, θ‐solvent); the intrinsic viscosity was determined in both solvents. The log [η] vs. log Mw dependence was curved in all cases, departures from linearity due to branching increased with increasing molar mass. The degree of branching was estimated using the viscometric method consisting in the determination of the intrinsic viscosity in two solvents with sufficiently different values of the MARK‐HOUWINK exponent. The degree of branching of macromolecules under the conditions used is essentially determined by the length of the primary chain given by the regulator concentration in the polymerization mixture and by conversion. In the emulsion system used the degree of branching does not depend significantly on the polymerization conversion if the latter is lower than 50%, but increases considerably at higher conversions.