Binding of two spin-labelled derivatives of chlorpromazine to human erythrocytes

The binding to human intact erythrocytes of two different spin-labelled derivatives of chlorpromazine has been studied. The influence of the positively charged side chain of the drug has been the focus of our attention. The positively charged amphiphilic compound (spin derivative I) is water-soluble up to 80 microM at pH values below 5.9. The apolar analogue (spin derivative II) aggregates in aqueous buffer from the lowest concentration tested. Both spin derivatives undergo a slow reduction inside the erythrocyte. The reduced nitroxides are readily reoxidized by adding a low, non-quenching, concentration of potassium ferricyanide to the intact erythrocytes. The fractions of spin label I and II bound to the erythrocyte membrane or to the erythrocyte-extracted lipids remain constant as a function of the temperature (3-42 degrees C) and as a function of the concentration of the spin label up to 150 microM. E.s.r. spectra of both spin labels show a two-component lineshape when they are bound to intact erythrocytes. Below 35 degrees C for the positively charged spin probe, and below 32 degrees C for the apolar spin probe, the simulation of the lineshape shows that more than 50% of the spectrum originates from a slow-motion component. This slow-motion component is also found in erythrocyte-extracted lipids probed by the positively charged spin label below 25 degrees C. In contrast, no slow-motion component is detected in the range 4-40 degrees C for the apolar spin label in erythrocyte-extracted lipids. In this environment the apolar probe experiences a single fast anisotropic motion with an exponential dependence on 1/temperature. Detailed lineshape simulations take into account the exchange frequency between binding sites where the probe experiences a fast motion and binding sites where it experiences a slow motion. The exchange frequency is strongly temperature-dependent. Characterization of the different motions experienced inside the different locations has been achieved and compared for whole erythrocytes and for the extracted lipids. The biochemical nature of the binding sites (membrane protein/acidic phospholipid) giving rise to the slow-motion component is discussed as a function of the polarity of the spin-labelled drug and as a function of the temperature controlling the fluidity of the lipid bulk and influencing the distribution of the drug inside the membrane.

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Self-assembly of chiral fluorescent nanoparticles based on water-soluble L-tryptophan derivatives of p-tert-butylthiacalix[4]arene

Beilstein Journal of Nanotechnology ◽

10.3762/bjnano.8.184 ◽

2017 ◽

Vol 8 ◽

pp. 1825-1835 ◽

Cited By ~ 4

Author(s):

Pavel L Padnya ◽

Irina A Khripunova ◽

Olga A Mostovaya ◽

Timur A Mukhametzyanov ◽

Vladimir G Evtugyn ◽

...

Keyword(s):

Electron Microscopy ◽

Self Assembly ◽

Water Soluble ◽

Fluorescent Nanoparticles ◽

Spectral Emission ◽

Chiroptical Properties ◽

Transmission Electron ◽

Derivatives Of ◽

Tryptophan Derivatives ◽

Positively Charged

New water-soluble tetra-substituted derivatives of p-tert-butylthiacalix[4]arene containing fragments of L-tryptophan in cone and 1,3-alternate conformations were obtained. It was shown that the resulting compounds form stable, positively charged aggregates of 86–134 nm in diameter in water at a concentration of 1 × 10−4 M as confirmed by dynamic light scattering, scanning electron microscopy and transmission electron microscopy. It was established that these aggregates are fluorescently active and chiral. A distinctive feature of the compounds is the pronounced dependence of their spectral (emission and chiroptical) properties on the polarity of the solvent and the length of the linker between the macrocyclic and fluorophore parts of the molecule.

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Some chemical and analytical aspects of polysaccharide modifications. IV. Electron spin resonance studies of nitroxide-labelled chitin and chitosan derivatives

Canadian Journal of Chemistry ◽

10.1139/v84-160 ◽

1984 ◽

Vol 62 (5) ◽

pp. 975-980 ◽

Cited By ~ 10

Author(s):

Manssur Yalpani ◽

Laurance D. Hall

Keyword(s):

Spin Label ◽

Water Soluble ◽

Spin Labels ◽

Chitosan Derivatives ◽

Terminal Galactose ◽

Spin Resonance ◽

Nitroxide Spin Labels ◽

Covalently Linked ◽

Chitin And Chitosan ◽

Probe Spin

Nitroxide spin labels have been attached to chitin, chitosan, and their derivatives in order to investigate the solution and gel characteristics of these polymers. Thus, chitin was nonselectively acylated using the chloroacetamide label 3 to afford. the corresponding nitroxide derivative 4. Selective and nonselective labelling of chitosan was accomplished either via reductive alkylation using the keto label 5 and sodium cyanoborohydride or via a chitosan sulfate intermediate using labels 3 or 5. Two branched water soluble chitosan derivatives, carrying C-6 oxidized, terminal galactose side chains were selectively labelled by reductive animation using the amine label 13 to yield derivatives 14 and 15. Motional correlation values of the covalently-linked nitroxide moieties were shown to reflect the nature of the linkage between spin label and polymer, as well as structural differences between the branch residues of derivatives 14 and 15. The spin-probe – spin-label method was employed to demonstrate structural heterogeneities for the chitosan derivatives 7 and 15.

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Synthesis of Water Soluble Spin Labeled Glucose Derivatives as Potential NMR Contrast Enhancing Agents

Zeitschrift für Naturforschung B ◽

10.1515/znb-1986-1017 ◽

1986 ◽

Vol 41 (10) ◽

pp. 1293-1305 ◽

Cited By ~ 10

Author(s):

George Sosnovsky ◽

N. Uma Maheswara Rao ◽

Jan Lukszo ◽

Robert C. Brasch

Keyword(s):

Glucuronic Acid ◽

Water Soluble ◽

Spin Labels ◽

Proton Relaxation ◽

Spin Lattice ◽

Synthetic Methodologies ◽

New Compounds ◽

Derivatives Of ◽

Glucose Derivatives

AbstractSynthetic methodologies for the preparation of nitroxyl labeled derivatives of D -(+)-glucose, α -D -(+)-m ethylglycoside, 2-amino-2-deoxy-D -(+)-glucose, and D -(+)-glucuronic acid are presented. The spin labels in these compounds are attached variably at the 1, 2, 3, and 6 positions of the glucose framework. These new compounds, being water soluble and producing marked enhancement of spin-lattice (T ,) and spin-spin (T2) proton relaxation in deionized water and human plasma have potential utility as contrast altering pharmaceuticals for magnetic resonance imaging and as spin probes in biomolecular research. These spin labeled carbohydrates may demonstrate in vivo biodistribution characteristics reflecting tissue-specific differences in glucose metabolism .

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Comparison of the dimensions of the combining sites of the dinitrophenyl-binding immunoglobulin A myeloma proteins MOPC 315, MOPC 460 and XRPC 25 by spin-label mapping

Biochemical Journal ◽

10.1042/bj1650199 ◽

1977 ◽

Vol 165 (2) ◽

pp. 199-206 ◽

Cited By ~ 13

Author(s):

Keith J. Willan ◽

Derek Marsh ◽

Christopher A. Sunderland ◽

Brian J. Sutton ◽

Simon Wain-Hobson ◽

...

Keyword(s):

Binding Sites ◽

Immunoglobulin A ◽

Binding Activity ◽

The Other ◽

Spin Labels ◽

Metal Site ◽

Myeloma Proteins ◽

Spin Resonance ◽

Mouse Immunoglobulin ◽

Positively Charged

The mouse immunoglobulin A myeloma proteins MOPC 315, MOPC 460 and XRPC 25 all possess dinitrophenyl (Dnp)-binding activity. Differences in specificities were shown by measuring the affinities of a variety of haptens. By using a series of Dnp-spin-labelled haptens, the dimensions of the binding sites of the three myeloma proteins were compared by the method described for protein MOPC 315 [Sutton, Gettins, Givol, Marsh, Wain-Hobson, Willan & Dwek (1977) Biochem. J.165, 177–197]. The dinitrophenyl ring is rigidly held in all three sites. The depths of the sites are all 1.1–1.2nm, but there are differences in the lateral dimensions at the entrance to the sites. For protein XRPC 25 these dimensions are 0.75nm×0.8nm, which may be compared with 0.85nm×1.1nm for protein MOPC 315 and ≥1.0nm×1.1nm for protein MOPC 460. The site in protein MOPC 460 is more symmetrical with respect to the plane of the dinitrophenyl ring than in either of the other two myeloma proteins and also allows greater penetration of solvent. In protein XRPC 25 a positively charged residue was located at the entrance to the site, similarly positioned to that reported for protein MOPC 315 [Sutton, Gettins, Givol, Marsh, Wain-Hobson, Willan & Dwek (1977) Biochem. J.165, 177–197]. All three proteins possess lanthanide-binding sites, but only in protein MOPC 315 is there antagonism between lanthanide and hapten binding. However, the effects of the diamagnetic La(III) on the electron-spin-resonance spectra of bound Dnp spin labels in both proteins MOPC 460 and XRPC 25 suggest an interaction between the two sites. Comparison of this effect with that caused by the addition of the paramagnetic Gd(III) enables the distance between the lanthanide- and hapten-binding sites to be calculated. In both proteins MOPC 460 and MOPC 315 the metal site is approx. 1.0nm from the nitroxide moiety of the spin-labelled hapten, but in protein XRPC 25 this distance is at least 2.0nm.

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Potential anticonvulsants: Substituted N-benzylidene derivatives of 10-(4-aminopiperazino)-10,11-dihydrodibenzo[b,f]thiepins

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19831173 ◽

1983 ◽

Vol 48 (4) ◽

pp. 1173-1186 ◽

Cited By ~ 2

Author(s):

Václav Bártl ◽

Jiří Holubek ◽

Emil Svátek ◽

Marie Bartošová ◽

Miroslav Protiva

Keyword(s):

Acute Toxicity ◽

Water Soluble ◽

Hypotensive Activity ◽

Anticonvulsant Effect ◽

Maximal Electroshock ◽

Soluble Salts ◽

Sleeping Time ◽

Central Depression ◽

Derivatives Of ◽

Electroshock Seizures

Reactions of 10-(4-aminopiperazino)-10,11-dihydrodibenzo[b,f]thiepins XIVa-XIVd with benzaldehyde, 3,4-dimethoxybenzaldehyde, 4-dimethylaminobenzaldehyde, salicylaldehyde, 3-ethoxy-4-hydroxybenzaldehyde, 2-(2-dimethylaminoethoxy)benzaldehyde, 3-(2-dimethylaminoethoxy)benzaldehyde and 3-ethoxy-4-(2-dimethylaminoethoxy)benzaldehyde afforded a series of 19 hydrazones IIIa-Xc. Some of them showed the expected anticonvulsant effect but only towards pentetrazole; antagonism of maximal electroshock seizures was not observed. In general, the products have a character of tranquillizers: in higher does they produce central depression, potentiate the thiopental sleeping time, have hypothermic action; in single cases antiamphetamine, antireserpine, antihistamine and cataleptic effects were observed. The water-soluble salts of the basic hydrazones VIIIa, VIIIc, IXc and Xc, administered parenterally, showed a rather high acute toxicity and revealed also adrenolytic and hypotensive activity.

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Tuning of Electronic Properties in Conducting Polymers

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc20011208 ◽

2001 ◽

Vol 66 (8) ◽

pp. 1208-1218 ◽

Cited By ~ 3

Author(s):

Guofeng Li ◽

Mira Josowicz ◽

Jiří Janata

Keyword(s):

Hydrogen Bonding ◽

Binding Site ◽

Binding Sites ◽

Polymer Chains ◽

Electronic Transitions ◽

Weakly Bound ◽

Ordered Structures ◽

Doped Polymer ◽

Positively Charged ◽

Repeated Cycling

Structural and electronic transitions in poly(thiophenyleneiminophenylene), usually referred to as poly(phenylenesulfidephenyleneamine) (PPSA) upon electrochemical doping with LiClO4 have been investigated. The unusual electrochemical behavior of PPSA indicates that the dopant anions are bound in two energetically different sites. In the so-called "binding site", the ClO4- anion is Coulombically attracted to the positively charged S or N sites on one chain and simultaneously hydrogen-bonded with the N-H group on a neighboring polymer chain. This strong interaction causes a re-organization of the polymer chains, resulting in the formation of a networked structure linked together by these ClO4- Coulombic/hydrogen bonding "bridges". However, in the "non-binding site", the ClO4- anion is very weakly bound, involves only the electrostatic interaction and can be reversibly exchanged when the doped polymer is reduced. In the repeated cycling, the continuous and alternating influx and expulsion of ClO4- ions serves as a self-organizing process for such networked structures, giving rise to a diminishing number of available "non-binding" sites. The occurrence of these ordered structures has a major impact on the electrochemical activity and the morphology of the doped polymer. Also due to stabilization of the dopant ions, the doped polymer can be kept in a stable and desirable oxidation state, thus both work function and conductivity of the polymer can be electrochemically controlled.

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A spin label study of the thyroid hormone-binding sites in human plasma thyroxine transport proteins.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)70053-2 ◽

1981 ◽

Vol 256 (2) ◽

pp. 831-836

Author(s):

S.Y. Cheng ◽

G. Rakhit ◽

F. Erard ◽

J. Robbins ◽

C.F. Chignell

Keyword(s):

Thyroid Hormone ◽

Human Plasma ◽

Spin Label ◽

Binding Sites ◽

Transport Proteins ◽

Hormone Binding ◽

Label Study

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Antioxidant Network Based on Sulfonated Polyhydroxyalkanoate and Tannic Acid Derivative

Bioengineering ◽

10.3390/bioengineering8010009 ◽

2021 ◽

Vol 8 (1) ◽

pp. 9

Author(s):

Laura Brelle ◽

Estelle Renard ◽

Valerie Langlois

Keyword(s):

Gallic Acid ◽

Tannic Acid ◽

Water Soluble ◽

Gel Formation ◽

Ene Reaction ◽

Inorganic Cations ◽

Medium Chain Length ◽

Physically Crosslinked ◽

The Stability ◽

Derivatives Of

A novel generation of gels based on medium chain length poly(3-hydroxyalkanoate)s, mcl-PHAs, were developed by using ionic interactions. First, water soluble mcl-PHAs containing sulfonate groups were obtained by thiol-ene reaction in the presence of sodium-3-mercapto-1-ethanesulfonate. Anionic PHAs were physically crosslinked by divalent inorganic cations Ca2+, Ba2+, Mg2+ or by ammonium derivatives of gallic acid GA-N(CH3)3+ or tannic acid TA-N(CH3)3+. The ammonium derivatives were designed through the chemical modification of gallic acid GA or tannic acid TA with glycidyl trimethyl ammonium chloride (GTMA). The results clearly demonstrated that the formation of the networks depends on the nature of the cations. A low viscoelastic network having an elastic around 40 Pa is formed in the presence of Ca2+. Although the gel formation is not possible in the presence of GA-N(CH3)3+, the mechanical properties increased in the presence of TA-N(CH3)3+ with an elastic modulus G’ around 4200 Pa. The PHOSO3−/TA-N(CH3)3+ gels having antioxidant activity, due to the presence of tannic acid, remained stable for at least 5 months. Thus, the stability of these novel networks based on PHA encourage their use in the development of active biomaterials.

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Solubilization of Charged Porphyrins in Interpolyelectrolyte Complexes: A Computer Study

Polymers ◽

10.3390/polym13040502 ◽

2021 ◽

Vol 13 (4) ◽

pp. 502

Author(s):

Karel Šindelka ◽

Zuzana Limpouchová ◽

Karel Procházka

Keyword(s):

Dissipative Particle Dynamics ◽

Water Soluble ◽

Coarse Grained ◽

Core Shell ◽

Computer Study ◽

Interpolyelectrolyte Complex ◽

The Core ◽

Porphyrin Derivatives ◽

Oppositely Charged ◽

Positively Charged

Using coarse-grained dissipative particle dynamics (DPD) with explicit electrostatics, we performed (i) an extensive series of simulations of the electrostatic co-assembly of asymmetric oppositely charged copolymers composed of one (either positively or negatively charged) polyelectrolyte (PE) block A and one water-soluble block B and (ii) studied the solubilization of positively charged porphyrin derivatives (P+) in the interpolyelectrolyte complex (IPEC) cores of co-assembled nanoparticles. We studied the stoichiometric mixtures of 137 A10+B25 and 137 A10−B25 chains with moderately hydrophobic A blocks (DPD interaction parameter aAS=35) and hydrophilic B blocks (aBS=25) with 10 to 120 P+ added (aPS=39). The P+ interactions with other components were set to match literature information on their limited solubility and aggregation behavior. The study shows that the moderately soluble P+ molecules easily solubilize in IPEC cores, where they partly replace PE+ and electrostatically crosslink PE− blocks. As the large P+ rings are apt to aggregate, P+ molecules aggregate in IPEC cores. The aggregation, which starts at very low loadings, is promoted by increasing the number of P+ in the mixture. The positively charged copolymers repelled from the central part of IPEC core partially concentrate at the core-shell interface and partially escape into bulk solvent depending on the amount of P+ in the mixture and on their association number, AS. If AS is lower than the ensemble average ⟨AS⟩n, the copolymer chains released from IPEC preferentially concentrate at the core-shell interface, thus increasing AS, which approaches ⟨AS⟩n. If AS>⟨AS⟩n, they escape into the bulk solvent.

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