Pyridyl Side Chain Research Articles

Unique Crystal Structure of a Self-Assembled Dinuclear Cu Peptoid Reveals an Unusually Long Cu···Cu Distance.

Studies on a series of molecular dicopper peptoid complexes showed that the Cu···Cu distances measured in X-ray single-crystal diffraction are typically in the range of 4.2-6.9 Å. Herein, we designed a new peptoid, L1, having 2,2'-bipyridine, propyl, and pyridyl side chains and discovered that although it forms a typical dicopper self-assembled structure (complex 1), the Cu···Cu distance is exceedingly long -8.043 Å. By analyzing its structure and surface properties in comparison to a control Cu-peptoid complex (2), in which the pyridyl side chain is modified by an ethanolic side chain, we suggest that the long Cu···Cu distance is contributed by the hydrophilic-hydrophobic interaction influenced by the pyridyl side chain and the steric hindrance of the propyl side chain. This result may motivate the use of dinuclear Cu peptoid complexes for wider applications, such as cooperative catalysis and luminescence.

Highly stable and tunable peptoid/hemin enzymatic mimetics with natural peroxidase-like activities

Developing tunable and stable peroxidase mimetics with high catalytic efficiency provides a promising opportunity to improve and expand enzymatic catalysis in lignin depolymerization. A class of peptoid-based peroxidase mimetics with tunable catalytic activity and high stability is developed by constructing peptoids and hemins into self-assembled crystalline nanomaterials. By varying peptoid side chain chemistry to tailor the microenvironment of active sites, these self-assembled peptoid/hemin nanomaterials (Pep/hemin) exhibit highly modulable catalytic activities toward two lignin model substrates 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 3,3’,5,5’-tetramethylbenzidine. Among them, a Pep/hemin complex containing the pyridyl side chain showed the best catalytic efficiency (Vmax/Km = 5.81 × 10−3 s−1). These Pep/hemin catalysts are highly stable; kinetics studies suggest that they follow a peroxidase-like mechanism. Moreover, they exhibit a high efficacy on depolymerization of a biorefinery lignin. Because Pep/hemin catalysts are highly robust and tunable, we expect that they offer tremendous opportunities for lignin valorization to high value products.

A Molecular Shape Recognitive HPLC Stationary Phase Based on a Highly Ordered Amphiphilic Glutamide Molecular Gel.

Chiral glutamide-derived lipids form self-assembled fibrous molecular gels that can be used as HPLC organic phases. In this study, HPLC separation efficiency was improved through the addition of branched amphiphilic glutamide lipids to the side chains of a terminally immobilized flexible polymer backbone. Poly(4-vinylpyridine) with a trimethoxysilyl group at one end was grafted onto the surface of porous silica particles (Sil−VP15, polymerization degree = 15), and the pyridyl side chains were quaternized with a glutamide lipid having a bromide group (BrG). Elemental analysis indicated that the total amount of the organic phase of the prepared stationary phase (Sil−VPG15) was 38.0 wt%, and the quaternization degree of the pyridyl groups was determined to be 32.5%. Differential scanning calorimetric analysis of a methanol suspension of Sil−VPG15 indicated that the G moieties formed a highly ordered structure below the phase transition temperature even on the silica surface, and the ordered G moieties exhibited a gel-to-liquid crystalline phase transition. Compared with a commercially available octadecylated silica column, the Sil−VPG15 stationary phase showed high selectivity toward polycyclic aromatic hydrocarbons, and particularly excellent separations were obtained for geometrical and positional isomers. Sil−VPG15 also showed highly selective separation for phenol derivatives, and bio-related molecules containing phenolic groups such as steroids were successfully separated. These separation abilities are probably due to multiple interactions between the elutes and the highly ordered functional groups, such as the pyridinium and amide groups, on the highly ordered molecular gel having self-assembling G moieties.

Abstract 511: Targeted one-carbon (1C) metabolism inhibitors: Design, synthesis and biological evaluation of novel 5-substituted pyrrolo[3,2-d]pyrimidines with pyridyl- and ortho-fluoropyridyl glutamate side chains as selective folate receptors substrates

Abstract One-carbon (1C) metabolism, in tumor cells, provides basic metabolites needed for proliferation and is compartmentalized into the cytosol and mitochondria. The key enzymes in 1C metabolism are de novo purine biosynthesis catalyzing enzymes, glycinamide ribonucleotide formyl transferase (GARFTase) and 5-​aminoimidazole-​4-​carboxamide ribonucleotide formyltransferase (AICARFTase) and mitochondrial serine hydroxymethyltransferase 2 (SHMT2) involved in glycine synthesis and maintaining 1C pools. We have previously designed and evaluated a series of multitargeted 5-substituted pyrrolo[3,2-d]pyrimidine antifolates with a phenyl glutamate side-chain (AGF291, AGF300 and AGF299), which inhibited KB tumor cell growth. AGF291 inhibited the enzymes crucial for both cytosolic and mitochondrial 1C metabolism. However, these compounds also were transported via the ubiquitously expressed reduced folate carrier (RFC) which can lead to dose-limiting toxicities as seen for classical antifolates such as pemetrexed (PMX). In this study, we designed conformationally restricted 5-substituted pyrrolo[3,2-d]pyrimidine antifolates with pyridyl glutamate side-chains (AGF363, AGF369 and AGF370) and ortho-fluoropyridyl glutamate side-chains (AGF377 and AGF379) to decrease normal cell uptake by the ubiquitously present RFC and maintain or increase transport via tumor-selective folate receptor α (FRα) and folate receptor β (FRβ). Replacing the phenyl with the pyridyl side-chain abrogated the transport via RFC, thereby improved (AGF363 vs AGF291) or maintained (AGF369 vs AGF300 and AGF370 vs AGF299) selective uptake by FRα and FRβ over RFC and showed potent KB tumor cell inhibition (AGF363, IC50 = 10.78 nM and AGF369, IC50 = 6.97 nM). The ortho-fluorinated pyridyl analogs were also selective for FRα and FRβ over RFC but showed moderate potency towards KB tumor cells. Overall, this study identified two key pharmacophores, i.e. the pyridyl and the o-fluoropyridyl side-chains, to obtain absolute selectivity for FRα and FRβ over RFC in the 5-substituted pyrrolo[3,2-d]pyrimidine series of 1Cmetabolism inhibitors. Further preclinical studies are underway to afford viable candidates for future clinical application of selective compounds without toxicities as an improvement of currently used agents. Citation Format: Arpit Doshi, Adrianne Wallace-Povirk, Carrie O'Connor, Zhanjun Hou, Larry Matherly, Aleem Gangjee. Targeted one-carbon (1C) metabolism inhibitors: Design, synthesis and biological evaluation of novel 5-substituted pyrrolo[3,2-d]pyrimidines with pyridyl- and ortho-fluoropyridyl glutamate side chains as selective folate receptors substrates [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 511.

Preparation and characterization of a novel hydrophilic interaction/ion exchange mixed-mode chromatographic stationary phase with pyridinium-based zwitterionic polymer-grafted porous silica.

Novel zwitterionic polymer-grafted porous silica microspheres were prepared by using sodium 2-bromoethanesulfonate to quaternize the pyridyl side chains of the polymer, which is anchored on the surface of porous silica. The separation behavior for toluene and benzoic acid proved that the zwitterionic polymer-grafted porous silica worked as a stationary phase in hydrophilic interaction/ion exchange mixed-mode chromatography. Compared with a conventional sulfobetaine-based zwitterion-grafted porous silica column, the prepared poly(vinylpyridinium ethanesulfonate)-immobilized porous silica afforded the highly selective separation of benzoic acid derivatives over a wide pH range, and the separation behavior was quite sensitive to the protonation state of the carboxylic acids. The high selectivity was attributed to the multiple interactions between the guest molecule and the zwitterionic groups on the polymer chains. The new zwitterionic stationary phase demonstrated excellent selectivity for hydrophilic biorelated molecules such as nucleobases and nucleosides.

Ionic hydrogenation-directed stereoselective construction of C-20(H) stereogenic center in steroid side chains: Scope and limitations

Stereoselective synthesis of steroidal C-20 tertiary alcohols with n-butyl, vinyl, furyl, thienyl, thiazolyl, aryl and pyridyl side chains via Grignard reaction or organolithium reagents have been realized starting from readily available 16-dehydropregnenolone acetate. The ionic hydrogenation of steroidal C-20 tertiary alcohols having furyl, methylfuryl, thienyl, phenyl and 4-methoxyphenyl side chains, resulted into the deoxygenated product with C-20 natural configuration in excellent yields. However, the alkyl, thiazolyl and pyridyl incorporated steroidal C-20 tertiary alcohols were failed under the same reaction condition. The scope of ionic hydrogenation is further highlighted through the stereoselective reduction of steroidal C-20,21-ene compounds with furyl, thienyl and 4-methoxyphenyl side chains gave the saturated compounds with C-20 natural configuration.

Structural Colored Balloons Responsive to pH Change

Structural colored balloons (SCBs) composed of poly(4-vinylpyridine-co-styrene) (P4VP-PS) exhibited a pH-controlled structural color change in the presence and absence of p-toluenesulfonic acid. The diameter of the SCBs increased and decreased under acidic and neutral conditions, respectively. The different colors exhibited at different pH values supposedly resulted from a change in the shell thickness not only due to the change in the diameter of the SCBs but also due to the uptake of p-toluenesulfonic acid to the pyridyl side chain of P4VP-PS.

Phase II Metabolic Pathways of Spectinamide Antitubercular Agents: A Comparative Study of the Reactivity of 4-Substituted Pyridines to Glutathione Conjugation.

Spectinamides are promising new semisynthetic anti-tubercular agents that are modified with a pyridyl side chain, which blocks native efflux from the tuberculosis cell. This study, describes the stability of an advanced panel of spectinamide analogs, with varying substitutions to the pyridyl side chain, to Phase-II conjugative metabolism by glucuronosyl transferase, sulfotransferase and glutathione-S-transferase enzymes using both human and rat S9 enzyme fractions. All solely 5-substituted pyridyl spectinamides exhibited complete stability towards Phase II conjugative enzymes. However, 4-chloro substituted pyridyl spectinamides were susceptible to glutathione conjugation with rates dependent on other substitutions to the pyridine ring. Electron donating 5-substitutions increased the propensity for glutathione conjugation and conversely the introduction of an electron withdrawing 5-fluoro group blocked all observed glutathione conjugation. Based on these Phase II metabolism studies, lead spectinamides 1329, 1445, 1599, 1661 and 1810 were found to have favorable properties for potential lead compounds with no Phase II liabilities.

Porous silica particles grafted with an amphiphilic side-chain polymer as a stationary phase in reversed-phase high-performance liquid chromatography.

The amphiphilic polymer-grafted silica was newly prepared as a stationary phase in high-performance liquid chromatography. Poly(4-vinylpyridine) with a trimethoxysilyl group at one end was grafted onto porous silica particles and the pyridyl side chains were quaternized with 1-bromooctadecane. The obtained poly(octadecylpyridinium)-grafted silica was characterized by elemental analysis, diffuse reflectance infrared Fourier transform spectroscopy and Brunauer-Emmett-Teller analysis. The degree of quaternization of the pyridyl groups on the obtained stationary phase was estimated to be 70%. The selective retention behaviors of polycyclic aromatic hydrocarbons including some positional isomers were investigated using poly(octadecylpyridinium)-grafted silica as an amphiphilic polymer stationary phase in high-performance liquid chromatography and results were compared with commercially available polymeric octadecylated silica and phenyl-bonded silica columns. The results indicate that the selectivity toward polycyclic aromatic hydrocarbons exhibited by the amphiphilic polymer stationary phase is higher than the corresponding selectivity exhibited by a conventional phenyl-bonded silica column. However, compared with the polymeric octadecylated silica phase, the new stationary phase presents similar retention behavior for polycyclic aromatic hydrocarbons but different retention behavior particularly for positional isomers of disubstituted benzenes as the aggregation structure of amphiphilic polymers on the surface of silica substrate has been altered during mobile phase variation.

Anticonvulsant activity of 1,2,4-triazine derivatives with pyridyl side chain: synthesis, biological, and computational study

A series of 5,6-bisaryl-1,2,4-triazine-3-thiol-substituted derivatives were synthesized by condensation of 1,2-diketones and thiosemicarbazide under microwave irradiations and subsequent alkylation of thiol group by chloromethylpyridinium chloride. Evaluation of anticonvulsant activity of compounds was performed by maximal electroshock and pentylenetetrazole-induced seizures tests. In order to evaluate their neuroprotective potential, the ability of compounds to inhibit soybean 15-lipoxygenase was also assessed. Further molecular modeling and docking study on Na+ channel and GABAA receptor was performed to elucidate their mechanisms of action and necessary interactions in the active site. Compounds 2c and 2d with bis(4-bromophenyl) and pyridyl substituents showed highest protection up to 70 and 80 % in PTZ and MES-induced seizures, respectively, compared to the control group. Molecular docking study revealed their possible antiseizure mechanism of action through GABAA receptor, and in silico assessment of their BBB permeability indicated them as CNS active agents.

Abstract LB-6: Non-covalent assembly of meso-tetra-4-pyridyl porphine with single-stranded DNA to form nano-sized complexes with pH-dependent DNA release and anti-tumor activity.

Abstract Porphyrin-based nanomaterials frequently require non-physiological conditions to promote non-covalent assembly limiting therapeutic utility. In the present studies, we demonstrate that single-stranded DNA (ssDNA) modulates non-covalent assembly of meso-tetra-4-pyridyl porphine (MTP) and that the resulting porphyrin:DNA nano-sized complexes (PDN) are stable indefinitely in aqueous solution under physiologically relevant conditions and undergo pH-dependent DNA release under moderately acidic conditions (pH 5.1) that protonate the pyridyl nitrogens of MTP. The biological utility of pH-dependent DNA release from PDN was demonstrated by endosomal release of DNA in cancer cells. PDN formation is DNA-dependent with the ratio of porphyrin:DNA being approximately two DNA nucleobases per porphyrin consistent with half the pyridyl side chains of MTP interacting with DNA nucleobases. Raman spectra display surface-enhanced features for the porphyrin in the context of PDN consistent with π-π stacking of porphyrins and DNA nucleobases being a principal driving force for PDN assembly, a result also consistent with enhanced PDN dissociation in more hydrophobic solvent systems. PDN produce reactive oxygen species (ROS) in a light-dependent manner under conditions that favor dissociation, such as in hydrophobic environments as occurs upon endocytosis or in the presence of hydrophobic solvents. PDN induce light-dependent cytotoxicity in vitro and anti-tumor activity towards bladder cancer xenografts in vivo. Light-dependent, PDN-mediated cell death resulted from ROS-mediated localized membrane damage with mass spectrometry confirming the generation of the lipid peroxidation products9- and 13-hydroxy octadecanoic acid. Our results demonstrate that PDN have properties useful for therapeutic applications, including cancer treatment. Citation Format: William H. Gmeiner, Supratim Ghosh, Kamil B. Ucer, Richard T. Williams, Ralph D'Agostino, Ken Grant, Joseph Sirintrapun, Michael Thomas, Roy Hantgan, Manish Bharadwaj. Non-covalent assembly of meso-tetra-4-pyridyl porphine with single-stranded DNA to form nano-sized complexes with pH-dependent DNA release and anti-tumor activity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-6. doi:10.1158/1538-7445.AM2013-LB-6

Self‐Assembly of Arylboronate Esters with Pyridyl Side Chains

AbstractBoronate esters that contain N‐donor groups are self‐complementary structures, which can assemble by means of dative boron–nitrogen bonds to form macrocycles or polymers. Herein, we describe the synthesis of dioxaborinanes and benzodioxaboroles containing pyridyl side chains. In the solid state, the dioxaborinanes were found to exist predominantly as monomers. Upon crystallization, aggregation into one‐dimensional polymers was observed, but only for boronate esters that contained electron‐withdrawing groups. The more Lewis acidic benzodioxaboroles, on the other hand, were found to form macrocycles both in solution and in the solid state.

A Small Molecule That Targets r(CGG)exp and Improves Defects in Fragile X-Associated Tremor Ataxia Syndrome

The development of small molecule chemical probes or therapeutics that target RNA remains a significant challenge despite the great interest in such compounds. The most significant barrier to compound development is defining which chemical and RNA motif spaces interact specifically. Herein, we describe a bioactive small molecule probe that targets expanded r(CGG) repeats, or r(CGG)(exp), that causes Fragile X-associated Tremor Ataxia Syndrome (FXTAS). The compound was identified by using information on the chemotypes and RNA motifs that interact. Specifically, 9-hydroxy-5,11-dimethyl-2-(2-(piperidin-1-yl)ethyl)-6H-pyrido[4,3-b]carbazol-2-ium binds the 5'CGG/3'GGC motifs in r(CGG)(exp) and disrupts a toxic r(CGG)(exp)-protein complex in vitro. Structure-activity relationship studies determined that the alkylated pyridyl and phenolic side chains are important chemotypes that drive molecular recognition of r(CGG)(exp). Importantly, the compound is efficacious in FXTAS model cellular systems as evidenced by its ability to improve FXTAS-associated pre-mRNA splicing defects and to reduce the size and number of r(CGG)(exp)-containing nuclear foci. This approach may establish a general strategy to identify lead ligands that target RNA while also providing a chemical probe to dissect the varied mechanisms by which r(CGG)(exp) promotes toxicity.

X-ray evidence for the relationship between pyridyl side chain basicity and the Z/E preferences of 5-halogen substituted(pyridin-2-yl)aminomethane-1,1-diphosphonic acids; implications for metal ions coordination in solution

The crystal structures of three salts ( 1-a−3-a), products of the reactions between 5-chloro ( 1), 5bromo ( 2) and 5-iodo ( 3) substituted (pyridin-2-yl)aminomethane-1,1-diphos phonic acids and 4aminopyridine were determined by single crystal X-ray diffraction and discussed with respect to molecular geometry and solid state organization. In all 1-a−3-a, bisphosphonate dianion adopts the opposite (E) conformation with respect to the C2 −N1 bond, compared with the parent zwitterion. This provides further evidence that int ermolecular N−H··· O hydrogen bonds involving both exocyclic and pyridinium N atoms as proton donors and an O atom of the phosphonic/phosphonate group as acceptor play a significant role in stabilizing the Z conformation of this particular subclass of acids. The solution behavior and complex-formation abilities of [(5-iodopyridin-2-yl)amino]methane-1,1 -diphosphonic acid (3) were also studied. Compound 3 exists in solution as the Z/E mixture. However, the barrier to rotation around t he C2 −N1 bond in 3 is lower, compared with 1 and 2. This is important for the complex-formation processes in the Zn(II), Mg(II) and Ca(II) solution s with 3.

Synthesis of Macrosphelides Containing a Heterocyclic Side Chain as a Novel Apoptosis Inducer

Synthesis of macrosphelides containing a pyridyl or benzimidazolyl side chain is described. The synthesis was accomplished through sequential assembling of suitable chiral blocks and ring-closing metathesis (RCM) with a high efficiency. These novel derivatives were evaluated on the apoptosis-inducing activity against human lymphoma cells.

Reactions of pyridyl side chain functionalized cyclopentadiene with ruthenium carbonyl

Reactions of the pyridyl side-chain-functionalized cyclopentadiene [C5H5CR2(CH2C5H4N)] [R 2 = Et2 (1), (CH2)4 (2)] with Ru3(CO)12 in refluxing xylene gave the new intramolecular C–H activated trinuclear product [μ-(C5H3N)CH2C(C2H5)2(C5H4)Ru(CO)]2Ru(CO)2 (3) and the normal dinuclear metal complex [(C5H4N)CH2C(CH2)4(C5H4)Ru(CO)]2(μ-CO)2 (4). The structures of the trinuclear complex 3 and dinuclear complex 4 were characterized by elemental analysis, IR spectra, 1H-NMR and X-ray diffraction. Reactions of the pyridyl side-chain-functionalized cyclopentadiene [C5H5CR2(CH2C5H4N)] [R 2 = Et2 (1), (CH2)4 (2)] with Ru3(CO)12 in refluxing xylene gave the new intramolecular C–H activated trinuclear product [μ-(C5H3N)CH2C(C2H5)2(C5H4)Ru(CO)]2Ru(CO)2 (3) and the normal dinuclear metal complex [(C5H4N)CH2C(CH2)4(C5H4)Ru(CO)]2(μ-CO)2 (4). The structures of the trinuclear complex 3 and dinuclear complex 4 were characterized by elemental analysis, IR spectra, 1H-NMR, and X-ray diffraction.

Reactions of Pyridyl Side Chain Functionalized Indenes with Ru3(CO)12

AbstractReactions of the pyridyl side chain functionalized indenes 3‐R‐C9H7 [R = (C5H4N)CH2CMe2 (1), (MeC5H3N)CH2CMe2 (2), (C5H4N)CH2 (6)] with Ru3(CO)12 in refluxing xylene gave the facial coordinated indenyl cluster [μ3‐η5:η2:η2‐(C5H3N)CH2Me2C(C9H6)]Ru4(μ3‐CO)(CO)7 (8), the syn‐η5:η6‐coordinated indenyl cluster [μ‐η5:η6‐(MeC5H3N)CH2CMe2(C9H6)Ru2(CO)3]2 (10), and the η1:η2‐coordinated indenyl complex[η2‐(C5H3N)CH2(C9H7)][η1:η2‐(C5H4N)CH2(C9H6)]Ru2(CO)4(18), respectively, in addition to the normal diruthenium complexes [(η5‐RC9H6)Ru(CO)]2(μ‐CO)2 [R = (C5H4N)CH2CMe2 (7), (MeC5H3N)CH2CMe2 (9), (C5H4N)CH2 (17)]. When the pyridyl side chains were replaced by other bulky groups [R = tBu (3), PhCH2Me2C (4), (C9H6N)CH2Me2C (5)], the similar syn‐η5:η6‐coordinated indenyl clusters 12, 14, and 16 were also obtained. When 1 or 2 were treated with Ru3(CO)12 in refluxing heptane, the ionic clusters {[(C5H4N)CH2Me2C(C9H6)]Ru(CO)2}+[HRu6(CO)18]– (19), [(C5H4N)CH2Me2C(C9H8)]+[HRu6(CO)18]– (20), and complex 8 or ionic clusters {[(MeC5H3N)CH2Me2C(C9H6)]Ru(CO)2}+[HRu6(CO)18]– (21) and [(MeC5H3N)CH2Me2C(C9H8)]+[HRu6(CO)18]– (22) were obtained. Similar treatment of 5 or 6 with Ru3(CO)12 in refluxing heptane gave the ionic clusters [(C9H6N)CH2Me2C(C9H8)]+[HRu6(CO)18]– (23) or {[η3‐(C5H4N)CH(C9H7)][η2‐(C5H4N)CH2(C9H7)]Ru(CO)}+[HRu6(CO)18]– (24), respectively, in addition to complex 18 in the latter case. The molecular structures of 8, 9, 10, 14, 17, 18, 21, 22, and 24 were determined by X‐ray diffraction analysis.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Orally active cephalosporins. Part 2: Synthesis, structure–activity relationships and oral absorption of cephalosporins having a C-3 pyridyl side chain

A series of 7β-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]cephalosporins having a pyridine ring connected through various spacer moieties at the C-3 position was designed and synthesized and evaluated for antibacterial activity and oral absorption in rats. All compounds showed potent antibacterial activity against Staphylococcus aureus, whereas antibacterial activity against Gram-negative bacteria was markedly influenced by the spacer moiety between the pyridine and cephem nucleus. Oral absorption was influenced by the position of the pyridine nitrogen as well as by the spacer moiety. Among these compounds, FR86830 (14 ), having a 4-pyridylmethylthio moiety at the C-3 position, showed the most well balanced activity and moderate oral absorption.

Copper ion complex formation of polypeptide containing side-chain pyridyl groups

The complex formation behaviors of an α-helical polypeptide containing pyridyl ligands in the side chains, poly (Nω-2-pyridylmethyl L-glutamine) (P2PG), were investigated by absorption and CD spectroscopy using Cu2+ ion as a guest molecule in 2,2,2-trifiuoroethanol solution. In the low Cu2+ ion concentration, P2PG exhibited the predominant formation of Cu2+ and two pyridyl side-chain complexes, involving a regular arrangement of the pyridyl side chains. On the other hand, the complexes were converted to Cu2+ and one pyridyl side-chain species with increasing Cu2+ ion concentration. The conversion was accompanied by the disappearance of the side-chain ordered structure without any changes in the backbone conformation. Moreover, the still remaining coordination sites of Cu2+ were capable of complexing monomer pyridine (Py) added as a second guest to form ternary complexes, P2PG-Cu2+-Py, following the reconstitution of the ordered structure on the periphery of the α-helix backbone. The unique characteristics of P2PG can be explained in terms of the restriction of the pyridyl side chains to form intramolecular chelate complexes, depending on the rigid α-helix conformation. © 1994 John Wiley & Sons, Inc.

Interaction between an α-Helical Polypeptide Containing Side-Chain Pyridyl Groups and Poly(4-vinylpyridine) in the Ternary Cu2+ Ion Complex

Abstract Interaction between a Cu2+-α-helical polypeptide containing side-chain pyridyl groups, poly(Nω-2-pyridylmethyl-l-glutamine) (P2PG), and poly(4-vinylpyridine) (P4VP) as a macromolecular guest was investigated by absorption and circular dichroism spectroscopies in 2,2,2-trifluoroethanol solutions. P4VP was added to the Cu2+-one pyridyl side chain complex system prepared in advance. One or two P4VP nitrogens could bind to the remaining coordination sites of the Cu2+ ion in the host system, yielding ternary Cu2+ complexes. The circular dichroism spectra of Cu2+-P2PG with P4VP indicated that P4VP might bind to the α-helix of P2PG in such a manner as to form a left-handed superhelix around the α-helical core resulting from the formation of ternary Cu2+ complexes. The structure of the interpolymer complex system was also investigated by a monolayer method. The surface pressure–area isotherm of a Cu2+-P2PG-P4VP monolayer and its hysteresis supported the formation of the supramolecular structure suggested by the spectroscopic methods.