Protonated Dimethylamino Group Research Articles

Adsorptive Removal of Bisphenol A by Polyethylene Meshes Grafted with an Amino Group-Containing Monomer, 2-(Dimethylamino)ethyl Methacrylate

The adsorptive removal of Bisphenol A (BPA) with the PE meshes photografted with 2-(dimethylamino)ethyl methacrylate (DMAEMA) was performed by varying the grafted amount, pH value, BPA concentration, and temperature, and the adsorption performance was correlated by the equilibrium, kinetic, and isotherm models. In addition, the regeneration of DMAEMA-grafted PE (PE-g-PDMAEMA) meshes was discussed from the repetitive adsorption/desorption process. The adsorption capacity had the maximum value at the grafted amount of 2.6 mmol/g and at the initial pH value of 8.0. The increase in the protonation of dimethylamino groups on grafted PDMAEMA chains and the dissociation of phenol groups of BPA present in the outer solution during the adsorption process results in the increase in BPA adsorption. The adsorption process followed the pseudo second-order equation. The BPA adsorption was enhanced by increasing the BPA concentration and the equilibrium data fit to Langmuir equation. The adsorption capacity stayed almost constant with the increase in the temperature, whereas the k2 value increased against the temperature. These results comprehensively emphasized that BPA adsorption occurred through the chemical interaction or ionic bonding of a BPA anion to a terminal protonated dimethylamino group. Desorption of BPA increased by increasing the NaOH concentration and BPA was entirely desorbed at more than 20 mM. The cycle of adsorption at pH 8.0 and desorption in a NaOH solution at 100 mM was repeated five times without loss or structural damage. These results indicate PE-g-PDMAEMA meshes can be used as a regenerative adsorbent for BPA removal from aqueous medium.

Development of recoverable adsorbents for Cr(VI) ions by grafting of a dimethylamino group-containing monomer on polyethylene substrate and subsequent quaternization

ABSTRACT A polymeric adsorbent for removal of hexavalent chromium (Cr(VI)) ions was developed by the photografting of 2-(dimethylamino)ethyl methacrylate (DMAEMA) to a polyethylene (PE) mesh and subsequent quaternization with iodoalkanes of different alkyl chain lengths. The grafting of DMAEMA and subsequent quaternization were verified by the FT-IR and XPS measurements. The Cr(VI) ion adsorption capacity of the DMAEMA-grafted PE meshes had the maximum value at the grafted amount of 2.6 mmol/g in a 0.20 mM K2Cr2O7 solution at pH 3.0 and 30°C. The adsorption behaviour obeyed the pseudo-second order kinetic model and well expressed by Langmuir isotherm. These results suggest that the Cr(VI) ion adsorption occurs through the electrostatic interaction mainly between protonated dimethylamino groups and hydrochromate (HCrO4 -) ions. The adsorption capacity of the quaternized PE-g-PDMAEMA meshes increased with an increase in the degree of quaternization and/or the alkyl chain length of the iodoalkanes used and the maximum adsorption ratio was obtained at the degree of quaternization of 54.2% for the iodoheptane-quaternized PE-g-PDMAEMA (PE-g-QC7PDMAEMA) mesh. This value was about 1.86 times higher than that of the PE-g-PDAMEMA mesh. Cr(VI) ions were successfully desorbed from the PE-g-PDMAEMA and PE-g-QC7PDMAEMA meshes in eluents such as NaOH, NaCl, and NH4Cl. In 0.50 M NaCl, 0.10 M NH4Cl, and 0.50 mM NaOH, the adsorption and desorption process was repeatedly performed without any considerable decrease and the desorption behaviour obeyed the pseudo-second order kinetic model. These results emphasise that the PE-g-PDMAEMA meshes and their quaternized products can be applied as an adsorbent for Cr(VI) ions.

Enhancement of Cr(VI) ion adsorption by two-step grafting of methacrylamide (MAAm) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) onto polyethylene plate

ABSTRACT Polyethylene (PE) plates grafted with a neutral hydrophilic monomer, methacrylamide (MAAm), and a cationic monomer, 2-(dimethylamino)ethyl methacrylate (DMAEMA), (PE-g-PMAAm)-g-PDMAEMA plates, were prepared by the two-step photografting. The Cr(VI) ion adsorption of the resultant (PE-g-PMAAm)-g-PDMAEMA plates was investigated as a function of the initial pH value, temperature, and grafted amounts of PMAAm and PDMAEMA. The adsorption capacity of the (PE-g-PMAAm)-g-PDMAEMA plates had the maximum at the initial pH value of 3.0 and the initial adsorption rate increased with the temperature and increased with the amount of grafted DMAEMA. This result suggests that protonated dimethylamino groups present in the inside of the grafted layer are increasingly involved in the Cr(VI) ion adsorption by the increase in the water absorptivity through the formation of the intermediate grafted layer of PMAAm. The maximum adsorption ratio of 0.510 was obtained for a (PE-g-PMAAm)-g-PDMAEMA plate with G MAAm = 30 μmol/cm2 and G DMAEMA = 1.7 μmol/cm2. The maximum adsorption capacity obtained in this study was comparable to or higher than those of other adsorbents for Cr(VI) ions. The adsorption behaviour obeyed the pseudo-second order kinetic model and was well described by the Langmuir isotherm model, suggesting that the adsorption of Cr(VI) ions occurs through the electrostatic interaction between protonated dimethylamino groups and ions. Cr(VI) ions were successfully desorbed in such eluents as NaCl, NaCl containing NaOH, NH4Cl, NH4Cl containing NaOH, and NaOH and (PE-g-PMAAm)-g-PDMAEMA plates were repeatedly used without considerable loss in the adsorption capacity.

How Strong is Hydrogen Bonding to Amide Nitrogen?

The protonation of the carboxamide nitrogen atom is an essential part of in vivo and in vitro processes (cis-trans isomerization, amides hydrolysis etc). This phenomenon is well studied in geometrically strongly distorted amides, although there is little data concerning the protonation of undistorted amides. In the latter case, the participation of amide nitrogen in hydrogen bonding (which can be regarded as the incipient state of a proton transfer process) is less well-studied. Thus, it would be a worthy goal to investigate the enthalpy of this interaction. We prepared and investigated a set of peri-substituted naphthalenes containing the protonated dimethylamino group next to the amide nitrogen atom ("amide proton sponges"), which could serve as models for the study of an intramolecular hydrogen bond with the amide nitrogen atom. X-Ray analysis, NMR spectra, basicity values as well as quantum chemical calculations revealed the existence of a hydrogen bond with the amide nitrogen, that should be attributed to the borderline between moderate and weak intramolecular hydrogen bonds (2-7 kcal ⋅ mol-1 ).

Hexavalent Cr ion adsorption and desorption behaviour of expanded poly(tetrafluoro)ethylene films grafted with 2-(dimethylamino)ethyl methacrylate

ABSTRACT A new polymeric adsorbent for Cr(VI) ions based on an expanded poly(tetrafluoroethylene) (ePTFE) film was prepared by the combined use of the pretreatment with oxygen plasma and photografting of 2-(dimethylamino)ethyl methacrylate (DMAEMA). The grafting of DMAEMA was characterized by XPS and FT-IR spectroscopic measurements. The adsorption behaviour of DMAEMA-grafted ePTFE (ePTFE-g-PDMAEMA) films was investigated as a function of the experimental parameters, such as the initial pH value, temperature, and grafted amount. The adsorption capacity and initial adsorption rate had the maximum values at the initial pH value of 3.0. On the other hand, the adsorption capacity became almost constant at temperatures higher than 30°C, although the adsorption rate increased over the temperature. The adsorption behaviour obeyed the pseudo-second-order kinetic model and well expressed by the Langmuir isotherm equation with higher correlation coefficients. These results indicate that the adsorption of Cr(VI) ions occurs through the electrostatic interaction between protonated dimethylamino groups on a grafted PDMAEMA chain and ions. Cr(VI) ions were successfully desorbed from Cr(VI)-loaded ePTFE-g-PDMAEMA films in the eluents, such as NaCl at 0.50 M, NH4Cl at 0.50M, and NaOH at 1.0 mM, and ePTFE-g-PDMAEMA films were repeatedly used for adsorption of Cr(VI) ions without appreciable loss in the adsorption capacity. It should be noted that Cr(VI) ion adsorptivity with a high initial rate was conferred to the ePTFE films. The results obtained in this study emphasize that ePTFE-g-PDMAEMA films can be applied as an adsorbent for Cr(VI) ions.

Tuning the pH Response of Weak Polyelectrolyte Brushes with Specific Anion Effects

The positively charged poly( N, N'-dimethylaminoethyl methacrylate) (PDMAEMA) brushes have been employed as model weak polyelectrolyte brushes (WPBs) to demonstrate the tuning of the pH response of WPBs with specific anion effects. The charge density of PDMAEMA brushes can be modulated by specific ion-pairing interactions between counterions and the protonated dimethylamino group; as a result, the strength of the pH response of PDMAEMA brushes can be tuned by specific anion effects. A more chaotropic counterion can more strongly interact with the protonated dimethylamino group, thereby more effectively neutralizing the positively charged group associated with the grafted weak polyelectrolyte chains and more remarkably suppressing the pH response of PDMAEMA brushes. Although the pH response of PDMAEMA brushes is insensitive to the anion identity at a low salt concentration, it can be tuned by specific anion effects at relatively high salt concentrations. Our study demonstrates that the pH-responsive properties of PDMAEMA brushes including hydration, conformation, oil wettability, and adhesion can be tuned by specific anion effects. The work presented here provides a method to tune the pH response of WPBs by the anion identity.

Two-step grafting of 2-hydroxyethyl methacrylate (HEMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) onto a polyethylene plate for enhancement of Cr(VI) ion adsorption

ABSTRACTPolyethylene (PE) plates grafted with a neutral monomer, 2-hydroxyethyl methacrylate (HEMA), and a cationic monomer, 2-(dimethylamino)ethyl methacrylate (DMAEMA), (PE-g-PHEMA)-g-PDMAEMA plates were prepared by the two-step photografting. The Cr(VI) ion adsorption behavior of the (PE-g-PHEMA)-g-PDMAEMA plates was investigated as a function of the amounts of grafted HEMA, amount of grafted DMAEMA, initial pH value, and temperature. The adsorption capacity of the DMAEMA-grafted PE (PE-g-PDMAEMA) and (PE-g-PHEMA)-g-PDMAEMA plates had the maximum value at the initial pH value of 3.0, independent of the temperature. The adsorption capacity of (PE-g-PHEMA)-g-PDMAEMA plates increased with the amount of grafted HEMA (GHEMA) in the first-step grafting. The increase in the water absorptivity of the grafted layers and thereby the increase in the degree of protonation of dimethylamino groups on grafted PDMAEMA chains were found to lead to the increase in the adsorption capacity. This adsorption capacity was higher than or comparable to those of other polymeric adsorbents for Cr(VI) ions. The Cr(VI) ion adsorption behavior on both PE-g-DMAEMA and (PE-g-PHEMA)-g-PDMAEMA plates obeyed the mechanism of the pseudo-second-order kinetic model and was well expressed by Langmuir isotherm. The high values of the Langmuir constant suggest that the adsorption of Cr(VI) ions occurs through an electrostatic interaction between protonated dimethylamino groups on grafted PDMAEMA chains and ions. Cr(VI) ions were successfully desorbed from PE-g-PDMAEMA and (PE-g-PHEMA)-g-PDMAEMA plates in eluents such as NaCl, NaCl containing NaOH, NH4Cl, NH4Cl containing NaOH, and NaOH.

Detection of an Iridium-Dihydrogen Complex: A Proposed Intermediate in Ionic Hydrogenation.

Addition of high pressures of H2 to five-coordinate [(tBu)4(POCOP)Ir(CO)(H)]OTf [(tBu)4(POCOP) = κ3-C6H3-2,6-(OP(tBu)2)2] complexes results in observation of two new iridium-dihydrogen complexes. If the aryl moiety of the POCOP ligand is substituted with an electron withdrawing protonated dimethylamino group at the para position, hydrogen coordination is enhanced. Five-coordinate Ir-H complexes generated by addition of triflic acid to (tBu)4(POCOP)Ir(CO) species show an Ir-H 1H NMR chemical shift dependence on the number of equivalents of acid present. It is proposed that excess triflic acid in solution facilitates triflate dissociation from iridium, resulting in unsaturated five-coordinate Ir-H complexes. The five-coordinate iridium-hydride complexes were found to catalyze H/D exchange between H2 and CD3OD. The existence of the dihydrogen complexes, as well as isotope exchange reactions, provide evidence for proposed ionic hydrogenation intermediates for glycerol deoxygenation.

Use of polyethylene films photografted with 2‐(dimethylamino)ethyl methacrylate as a potential adsorbent for removal of chromium (VI) from aqueous medium

ABSTRACTA new polymeric adsorbent material based on polyethylene (PE) was prepared by photografting of 2‐(dimethylamino)ethyl methacrylate (DMAEMA) as a positively chargeable monomer to a PE film. The effects of the experimental parameters, such as the pH value, temperature, and grafted amount on adsorption of chromium(VI) (Cr(VI)) ions were investigated for the DMAEMA‐grafted PE (PE‐g‐PDAMEMA) films. The maximum adsorption capacity was obtained at the initial pH value of 3.0 for a PE‐g‐PDMAEMA film with 1.8 mmol/g and the maximum adsorption capacity obtained was higher than or compatible to those of many of the other polymeric adsorbents prepared for Cr(VI) ions. The adsorption kinetics obeyed the mechanism of the pseudo‐second order kinetic model and adsorption of Cr(VI) ions on PE‐g‐PDMAEMA films was well expressed by the Langmuir isotherm model. A high Langmuir adsorption constant suggests that the adsorption of Cr(VI) ions occurs between protonated dimethylamino groups and ions mainly through the electrostatic interaction. Cr(VI) ions adsorbed were successfully desorbed from a PE‐g‐PDMAEMA film in solutions of NaCl, NH4Cl, NH4Cl containing NaOH, and NaOH and a PE‐g‐PDMAEMA film was regenerated and repeatedly used for adsorption of Cr(VI) ions without appreciable loss in the adsorption capacity. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43360.

Oxytetracycline interactions at the soil–water interface: Effects of environmental surfaces on natural transformation and growth inhibition of Azotobacter vinelandii

The mechanism of oxytetracycline (OTC) adsorption to a silty clay loam soil was investigated using sorption isotherm experiments, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction spectroscopy (XRD). Sorption data fit well to a cation-exchange capacity sorption model. Spectroscopic data indicate that the interactions between oxytetracycline and silty clay loam soil were primarily through electrostatic interactions between the protonated dimethylamino group of OTC and the negatively charged moieties on the surface of the soil. Based on XRD results, OTC adsorption appeared to inhibit the ethylene glycol solvation of the expandable clay minerals, suggesting that OTC had diffused into the clay interlayer space. The presence of adsorbed OTC did not significantly affect the transformation frequency of the soil bacterium Azotobacter vinelandii with plasmid DNA (soil alone 3 × 10(6) ± 4 × 10(6) and soil with adsorbed OTC 4 × 10(6) ± 0.5 × 10(6) ). Growth was inhibited by adsorbed OTC, although a greater mass of adsorbed OTC was required to achieve the same degree of inhibition as the system of dissolved OTC alone. These results suggest that the interactions of tetracyclines at the soil-water interface will affect the growth of sensitive microorganisms in soil microbial communities.

Dichloridobis{2-[(dimethyl-amino)-meth-yl]phen-yl}bis-{2-[(dimethyl-aza-nium-yl)meth-yl]phen-yl}di-μ-hydroxido-di-μ(3)-oxido-tetra-phenyl-tetra-tin(IV) dichloride deuterochloro-form deca-solvate.

The ladder-like structure of the tetranuclear title compound, [Sn4(C6H5)4Cl2O2(OH)2(C9H13N)2(C9H12N)2]Cl2·10CDCl3, consists of two five- and two six-coordinated SnIV atoms bridged by oxide or hydroxide groups. The chelating ligands reveal rather strong Sn—N bonds [2.517 (4) Å], but the protonated dimethylamino groups in the periphery of the complex show no interaction with the metal atoms. The complex cation is located on an inversion centre. The chloride anion is linked to the complex mol­ecule by strong intra­molecular O—H⋯Cl and N—H⋯Cl hydrogen bonds. Five independent deuterochloroform accompany the complex, two of them are disordered [occupancy ratios 0.63 (2):0.27 (2) and 0.60 (2):0.40 (2)].

Interactions of Oxytetracycline with a Smectite Clay: A Spectroscopic Study with Molecular Simulations

Binding of antibiotics to clay minerals can decrease both their physical and biological availability in soils. To elucidate the binding mechanisms of tetracycline antibiotics on smectite clays as a function of pH, we probed the interactions of oxytetracycline (OTC) with Na-montmorillonite (MONT) using X-ray diffraction (XRD), infrared (IR), and solid-state nuclear magnetic resonance (NMR) spectroscopies, and Monte Carlo molecular simulations. The XRD patterns demonstrate the presence of OTC in the MONT interlayer space at acidic pH whereas complexation of OTC by external basal and edge sites seems to prevail at pH 8. At both pH, the (1)H-(13)C NMR profile indicates restricted mobility of the adsorbed OTC species; and, -CH(3) deformation and C-N stretching IR vibration bands confirm a binding mechanism involving the protonated dimethylamino group of OTC. Changes in the (23)Na NMR environments are consistent with cation-exchange and cation complexation reactions at the different sites of adsorption. Molecular simulations indicate that MONT interlayer spacing and structural charge localization dictate favorable binding conformations of the intercalated OTC, facilitating multiple interactions in agreement with the spectroscopic data. Our results present complementary insights into the mechanisms of adsorption of TETs on smectites important for their retention in natural and engineered soil environments.

Analysis of Transient and Catalytic Desosamine-binding Pockets in Cytochrome P-450 PikC from Streptomyces venezuelae

The cytochrome P-450 PikC from Streptomyces venezuelae exhibits significant substrate tolerance and performs multiple hydroxylation reactions on structurally variant macrolides bearing the deoxyamino sugar desosamine. In previously determined co-crystal structures (Sherman, D. H., Li, S., Yermalitskaya, L. V., Kim, Y., Smith, J. A., Waterman, M. R., and Podust, L. M. (2006) J. Biol. Chem. 281, 26289-26297), the desosamine moiety of the native substrates YC-17 and narbomycin is bound in two distinct buried and surface-exposed binding pockets, mediated by specific interactions between the protonated dimethylamino group and the acidic amino acid residues Asp(50), Glu(85), and Glu(94). Although the Glu(85) and Glu(94) negative charges are essential for maximal catalytic activity of native enzyme, elimination of the surface-exposed negative charge at Asp(50) results in significantly enhanced catalytic activity. Nevertheless, the D50N substitution could not rescue catalytic activity of PikC(E94Q) based on lack of activity in the corresponding double mutant PikC(D50N/E94Q). To address the specific role for each desosamine-binding pocket, we analyzed the x-ray structures of the PikC(D50N) mutant co-crystallized with narbomycin (1.85A resolution) and YC-17 (3.2A resolution). In PikC(D50N), the desosamine moiety of both YC-17 and narbomycin was bound in a catalytically productive "buried site." This finding suggested a two-step substrate binding mechanism, whereby desosamine is recognized in the two subsites to allow the macrolide substrate to sequentially progress toward a catalytically favorable orientation. Collectively, the binding, mutagenesis, kinetic, and x-ray structural data suggest that enhancement of the catalytic activity of PikC(D50N) is due to the facilitated relocation of substrate to the buried site, which has higher binding affinity, as opposed to dissociation in solution from the transient "surface-exposed site."

Stability of Hoogsteen‐Type Triplexes – Electrostatic Attraction between Duplex Backbone and Triplex‐Forming Oligonucleotide (TFO) Using an Intercalating Conjugate

AbstractSyntheses are described for two novel twisted intercalating nucleic acid (TINA) monomers where the intercalator comprises a benzene ring linked to a naphthalimide moiety via an ethynediyl bridge. The intercalators Y and Z have a 2‐(dimethylamino)ethyl and a methyl residue on the naphthalimide moiety, respectively. When used as triplex‐forming oligonucleotides (TFOs), the novel naphthalimide TINAs show extraordinary high thermal stability in Hoogsteen‐type triplexes and duplexes with high discrimination of mismatch strands. DNA Strands containing the intercalator Y show higher thermal triplex stability than DNA strands containing the intercalator Z. This observation can be explained by the ionic interaction of the protonated dimethylamino group under physiological conditions, targeting the negatively charged phosphate backbone of the duplex. This interaction leads to an extra binding mode between the TFO and the duplex, in agreement with molecular‐modeling studies. We believe that this is the first example of an intercalator linking the TFO to the phosphate backbone of the duplex by an ionic interaction, which is a promising tool to achieve a higher triplex stability.

A new, highly stable cationic-thermosensitive microgel: Uniform isopropylacrylamide-dimethylaminopropylmethacrylamide copolymer particles

New monodisperse, thermosensitive, cationic microgel particles up to 1930 ± 56 nm in size were obtained by the dispersion copolymerization of N-isopropylacrylamide (NIPA) and N-3-dimethyl-aminopropylmethacrylamide (DMAPM). In the developed protocol, an amide based comonomer, DMAPM was tried as a new alternative material for introducing positive charge to the thermosensitive microgel. Poly(NIPA-co-DMAPM) microgel exhibited pH-sensitivity and the particle size linearly decreased with increasing pH. Poly(NIPA-co-DMAPM) microgel synthesized without making any pH adjustment in the aqueous medium exhibited colloidal stability between pHs 3 and 10 while similar cationic microgels were reported to be unstable at pHs higher than 6. The stronger cationic character of selected comonomer originated from its amide based structure (i.e. higher p K a of DMAPM) provided higher colloidal stability to the poly(NIPA-co-DMAPM) microgel. The interaction of poly(NIPA-co-DMAPM) particles with albumin was investigated by using plain poly(NIPA) particles as control material. The albumin adsorptions up to 96 mg/g particles were obtained at the isolelectric point via the reversible complexation between carboxyl groups of albumin and protonated dimethylamino groups on the particles. The albumin adsorption was effectively controlled by changing the surface characteristics of poly(NIPA-co-DMAPM) particles by both switches (i.e. pH and temperature). The hydrophilicity increase of particles induced by temperature decrease and the deprotonation of dimethylamino groups with increasing pH provided nearly quantitative albumin desorption from the poly(NIPA-co-DMAPM) particles. These advantages make poly(NIPA-co-DMAPM) microgel as a promising material for the development of new surface related biotechnological applications.

Acridinecarboxamide topoisomerase poisons: structural and kinetic studies of the DNA complexes of 5-substituted 9-amino-(N-(2-dimethylamino)ethyl)acridine-4-carboxamides.

For a series of antitumor-active 5-substituted 9-aminoacridine-4-carboxamide topoisomerase II poisons, we have used X-ray crystallography and stopped-flow spectrophotometry to explore relationships between DNA binding kinetics, biological activity, and the structures of their DNA complexes. The structure of 5-F-9-amino-[N-(2-dimethylamino)ethyl]-acridine-4-carboxamide bound to d(CGTACG)(2) has been solved to a resolution of 1.55 A in space group P6(4). A drug molecule intercalates between each of the CpG dinucleotide steps, its protonated dimethylamino group partially occupying positions close to the N7 and O6 atoms of guanine G2 in the major groove. A water molecule forms bridging hydrogen bonds between the 4-carboxamide NH and the phosphate group of the same guanine. Intercalation unwinds steps 1 and 2 by 12 degrees and 8 degrees, respectively compared with B-DNA, whereas the central TpA step is overwound by 10 degrees. Nonphenyl 5-substituents, on average, decrease mean DNA dissociation rates by a factor of three, regardless of their steric, hydrophobic, H-bonding, or electronic properties. Cytotoxicity is enhanced on average 4-fold and binding affinities rise by 3-fold, thus there is an apparent association between kinetics, affinity, and cytotoxicity. Taken together, the structural and kinetic studies imply that the main origin of this association is enhanced stacking interactions between the 5-substituent and cytosine in the CpG binding site. Ligand-dependent perturbations in base pair twist angles and their consequent effects on base pair-base pair stacking interactions may also contribute to the stability of the intercalated complex. 5-Phenyl substituents modify dissociation rates without affecting affinities, and variations in their biological activity are not correlated with DNA binding properties, which suggests that they interact directly with the topoisomerase protein.

Crystal structure of the topoisomerase II poison 9-amino-[N-(2-dimethylamino)ethyl]acridine-4-carboxamide bound to the DNA hexanucleotide d(CGTACG)2.

The structure of the complex formed between d(CGTACG)(2) and the antitumor agent 9-amino-[N-(2-dimethylamino)ethyl]acridine-4-carboxamide has been solved to a resolution of 1.6 A using X-ray crystallography. The complex crystallized in space group P6(4) with unit cell dimensions a = b = 30.2 A and c = 39.7 A, alpha = beta = 90 degrees, gamma = 120 degrees. The asymmetric unit contains a single strand of DNA, 1. 5 drug molecules, and 29 water molecules. The final structure has an overall R factor of 19.3%. A drug molecule intercalates between each of the CpG dinucleotide steps with its side chain lying in the major groove, and the protonated dimethylamino group partially occupies positions close to ( approximately 3.0 A) the N7 and O6 atoms of guanine G2. A water molecule forms bridging hydrogen bonds between the 4-carboxamide NH and the phosphate group of the same guanine. Sugar rings adopt the C2'-endo conformation except for cytosine C1 which moves to C3'-endo, thereby preventing steric collision between its C2' methylene group and the intercalated acridine ring. The intercalation cavity is opened by rotations of the main chain torsion angles alpha and gamma at guanines G2 and G6. Intercalation perturbs helix winding throughout the hexanucleotide compared to B-DNA, steps 1 and 2 being unwound by 8 degrees and 12 degrees, respectively, whereas the central TpA step is overwound by 17 degrees. An additional drug molecule, lying with the 2-fold axis in the plane of the acridine ring, is located at the end of each DNA helix, linking it to the next duplex to form a continuously stacked structure. The protonated N,N-dimethylamino group of this "end-stacked" drug hydrogen bonds to the N7 atom of guanine G6. In both drug molecules, the 4-carboxamide group is internally hydrogen bonded to the protonated N-10 atom of the acridine ring. The structure of the intercalated complex enables a rationalization of the known structure-activity relationships for inhibition of topoisomerase II activity, cytotoxicity, and DNA-binding kinetics for 9-aminoacridine-4-carboxamides.

A Mechanistic Study of the Hydrolytic Stability of Poly(2-(dimethylamino)ethyl methacrylate)

The hydrolytic stability of poly(2-(dimethylamino)ethyl methacrylate) was investigated and compared with the stability of its monomer 2-(dimethylamino)ethyl methacrylate (DMAEMA), with 2-(dimethylamino)ethyl isobutyrate (DMAEIB), representing the repeating unit in the polymer, and with the related 3-(dimethylamino)propyl methacrylate (DMAPMA) (H0/pH range −0.5 to +12, at 37 °C, in aqueous solution). At pH < 3, the unsaturated DMAEMA and DMAPMA were more stable than the saturated DMAEIB. At pH 4−8, DMAEMA and DMAEIB were equally stable, but less stable than DMAPMA. This has been ascribed to a coordination of the protonated dimethylamino group and the ester carbonyl, rendering the ester more susceptible to nucleophilic attack of a hydroxyl ion. At alkaline pH (>pKa) no differences in stability between the compounds were found. P(DMAEMA), either in its free form or complexed to DNA, was substantially more stable to hydrolytic degradation than DMAEMA and DMAEIB. Fluorescence measurements performed with a copolymer of DMAEMA and dansyl ethyl methacrylamide showed that the dielectric constant (εr) experienced in the environment of the polymer backbone, was low (about 7). This microenvironment might be the reason for the hydrolytic stability of the polymer, since the hydrolysis of the monomer decreased substantially with decreasing εr of the medium. Accelerated degradation (80 °C, pH 1 and 7) of p(DMAEMA) and poly(2-(dimethylamino)ethyl acrylate), p(DMAEA), showed that p(DMAEA) was more sensitive to hydrolysis. This can be explained by the assumption that, due to the lack of the methyl group, the εr in the environment of the acrylate backbone is higher than the εr in the environment of the p(DMAEMA) backbone.

Molecular Association of Water-Soluble Calixarenes with Several Stilbene Dyes and Its Application to the Facile Determination of Cationic Surfactant Concentrations

Abstract The molecular association of water-soluble p-sulfonatocalix[n]arenes (1n; n = 4, 6, and 8) with several stilbene dyes (D) has been studied by spectrophotometric and 1H NMR methods. It was found that 1n reacts in 1 : 1 stoichiometry with, D such as 4-[(4-dimethylamino)styryl]-1-methylpyridinium (St–4Me), 2-[(4-dimethylamino)styryl]-1-methylpyridinium (St–2Me) and 2-[(4-dimethylamino)styryl]-1-ethylpyridinium (St–2Et) iodides to form their complexes (1nD). The apparent association constants for 18-complexes are larger by about ten times than those of 14- and 16-complexes. Examinations of the CPK molecular models and the spectrophotometric studies suggested that 14 complexes D mainly with its 1-methyl- or 1-ethylpyridinium group, whereas 16 complexes D either with its pyridinium ring or with its protonated dimethylamino group in a similar probability, and in 18-complexes the molecule is wholly incorporated into the cavity of 18. The absorbance of D, which was decreased by association with 1n, was regenerated by the addition of other colorless cationic surfactants (A) such as cetylethyldimethylammonium ion. Studies on the substitution reaction of 1nD with A indicated that a 1 : 1 complex (1nA) is formed by releasing a free dye molecule (D). This was applied to a convenient determination of the cationic surfactant concentration in water.

Dopamine receptor blockade by imidoline and its proposed active conformation

Imidoline, 1-[2-(N,N-dimethylamino)ethyl]-3-m-chlorophenyl-2-imidazolidinone, has been found to be as potent as chlorpromazine in increasing striatal DOPA accumulation and prolactin secretion in vivo. In contrast, imidoline exhibited only weak inhibitory activity towards dopamine-sensitive adenylate cyclase and 3H-spiroperidol binding to striatal membranes in vitro. These neuroleptic effects in vivo are probably caused by blockade of dopamine receptors, since imidoline did not deplete the striatum of dopamine. Imidoline is of interest because its structure is distinct from those of other neuroleptics. A proposed active conformation involves intramolecular hydrogen bonding between the protonated dimethylamino group and the oxygen of the imidazolidinone ring. The spatial relationship between the amine nitrogen and phenyl ring in this conformation allows proper fit of imidoline with key dimensions described for the dopamine receptor.