Boronic acid hydrogen bonding in encapsulation complexes

Hydrogen bonding is a key determinant of much macromolecular structure in nature, but individual donor and acceptor pairs are rarely observed in solution. Their weak interactions result in nanosecond lifetimes and rapid exchange of partners. Reversible encapsulation isolates molecules in very small spaces for milliseconds to hours and allows their characterization by NMR methods. Here we report a competitive study of hydrogen-bonding functions--carboxylic acids, primary amides, and boronic acids--within a multicomponent capsular assembly. The pairwise co-encapsulation of these molecules allows the direct observation of homodimeric boronic acids and their heterodimeric complexes with carboxylic acids and primary amides. The efficiency of boronic acids as hydrogen-bonding partners derives from their adaptable structures rather than from their intrinsic acid/base properties.     

Infrared spectrophotometric investigations in polarized light of the clathrate formed by Ni(γ-picoline)4(NCS)2 and α-methylnaphthalene

Infrared spectra in polarized light of crystals of the clathrate by Ni (γ-picoline)₄(NCS)₂ and α-methylnaphthalene were investigated. A model is proposed in which two pairs of γ-picoline molecules have non-equivalent orientation. The α-methylnaphthalene molecule is probably sandwiched between γ-picoline molecules.     

Dynamic Equilibrium between a Supramolecular Capsule and Bowl Generated by Inter‐ and Intramolecular Metal Clipping

The metal‐induced self‐assembly of a resorcin[4]arene derivative 1 that has four pyridine units as pendent groups and two equivalents of [M(dppp)(OTf)₂] (M=Pd, Pt) results in a dynamic equilibrium between an interclipped supramolecular capsule 3 and an intraclipped bowl 4 in nitromethane, although the interclipped capsule 3 is formed as a sole adduct in chloroform/methanol and the intraclipped bowl 4 is formed exclusively in an aqueous phase. This demonstrates how metal‐induced self‐assembly can be tuned by subtle changes in the solvent system. The coexistence of the two structures in nitromethane was characterized by NMR spectroscopy and coldspray ionization mass spectrometry (CSI‐MS). The crystal structure of the interclipped capsule 3 b , which is composed of two units of ligand 1 and four Pt^II ions, reveals the capsule cavity to have nanoscale dimensions of 15×20 Å. NMR spectra show that the dynamic equilibrium between 3 and 4 is dependent on concentration and temperature. Temperature‐dependent ¹H NMR spectroscopy was carried out from 273 to 343 K to verify the thermodynamic parameters that control the dynamic equilibrium process; the conversion from the interclipped supramolecular capsule 3 a to the intraclipped bowl 4 a is entropically favored and enthalpically disfavored. The rotational barrier of the restricted rotation of pyridine units in the intraclipped bowl 4 was determined by line‐shape analysis.     

Paper Chromatographic Behavior of Some Tertiary Amine Pollutants and an Attempt at Structure-Activity-Correlation

Abstract

Ascending paper chromatography of some pesticides and toxicants containing a tertiary amino group has been performed to record their mobilities in acidic, basic and saline waters and some common organic solvents, Several binary separations of these pollutants have been achieved. The important separations are summarized below:

Amitrole from azobenzene, bavistin, calixin, 2,4-Lutidine, 2,6-Lutidine, N-ethylmorpholine, β-picoline, γ-picoline and quinoline; Azobenzene from bavistin, calixin, 2,4-Lutidine, 2,6-Lutidine, β-picoline, γ-picoline, pyridine and quinoline; Bavistin from 2,4-Lutidine, 2,6-Lutidine, β-picoline, γ-picoline and quinoline; and Quinoline from 2,4-Lutidine, 2,6-Lutidine, β-picoline, γ-picoline and N-ethylmorpholine from binary mixtures. An attempt at structure-activity-correlation reveals that the physical forces responsible for both the chromatographic behaviour as well as the toxicity are almost identical and the most important common physical interaction seems to be the hydrogen-bonding.     

The problem of the azatropylium ion: Hydrogen elimination from the molecular ion of γ-picoline

Comparison of the mass spectrum of γ-picoline with that of analogues, specifically deuterated in the methyl group, the ring or both, has shown that the molecular ion loses the α,β and methyl hydrogen atoms (ω-hydrogen') in the ratio 1.43: 1: 1. 13. The same trend is found for the elimination of HCN from the molecular ion. Moreover, a value of 1.52 is found for the isotope effect, expressing the favoured loss of H over D, irrespective of its position.     

Host-guest assembly of ligand systems for metal ion complexation. Synergistic solvent extraction of copper(II) and silver(I) by 1,4,8,11-tetrabenzyl-1,4,8,11-tetraazacyclodecane in combination with carboxylic acids

Host-guest formation between 1,4,8,11-tetrabenzyl-1,4,8,11-tetraazacyclodecane (1) and lipophilic organic carboxylic acids in chloroform has been investigated and the effect of such ligand assembly on the solvent extraction of copper(II) and silver(I) has been probed. NMR titration experiments in the absence of a metal ion confirm the formation of weak 1:1 and 1:2 (macrocycle:carboxylic acid) assemblies in CDCl(3) between 1 and palmitic (hexadecanoic) acid or 4-tert-butylbenzoic acid while difunctional salicylic acid showed a 1 [ratio] 2 interaction that is somewhat stronger. The interaction between the former two acids and the tetra-N-benzylated macrocycle is significantly less than that reported previously for its non-substituted parent, cyclam; a result that likely reflects the presence of the less-basic, more sterically hindered tertiary nitrogens in 1 relative to the secondary nitrogens present in cyclam. Carboxylic acid-containing assemblies of this type have been used as extractants in a series of solvent extraction (water/chloroform) experiments. From both previous observations as well as from entropy considerations, it was anticipated that the use of a host-guest assembly of the above type for metal-ion complexation might contribute to enhanced metal ion binding (and concomitant enhanced metal ion extraction). Such behaviour is postulated to arise from the components of the coordination sphere being, at least in part, assembled for complex formation. In accord with this, the use of the ligand assembly involving palmitic acid/macrocycle 1 was found to lead to enhanced (synergistic) extraction of copper(II) at a metal ion concentration of 10(-3) mol dm(-3) while, for silver(I), synergism was somewhat marginal at this concentration but was clearly apparent under related conditions when the silver concentration was reduced to 10(-4) mol dm(-3). Similar behaviour towards silver was also observed when 4-tert-butylbenzoic acid was substituted for palmitic acid, while the use of salicylic acid resulted in enhanced (synergistic) extraction at both metal ion concentrations.     

Methyl group rotation barrier in γ-picoline

Ab initio calculations on γ-picoline predict a small methyl rotational barrier of approximately 14 calories mole^?1 in good agreement with the experimental value of 13.7 calories mole^?1 [1].     

State in solution, structure, and regioselectivity of reactions of the lithium 1-(2-methoxyphenyl)-3,3-diphenylpropyne derivative

According to the spectrophotometric data, the lithium 1-(2-methoxyphenyl)-3,3-diphenylpropyne derivative in diethyl ether exists as contact ion pairs, while in THF, according to the spectrophotometric and¹³C NMR data, solvent-separated ion pairs are predominantly formed. According to the¹³C NMR data, the carbanion in the solventseparated ion pairs has a structure close to the propargylic type. The regioselectivity of reactions of the lithium derivative with ethyl halides in diethyl ether, THF, and hexamethyphosphoramide, with benzyl chloride in the first two solvents, and with methanol in THF were studied. The protonation with methanol proceeds exclusively at the allenylic center (C-1) while the ethylation and especially benzylation proceed predominantly at the propargylic center (C-3). The selectivity of ethylation of the propargylic center of both solvent-separated ion pairs in THF and contact ion pairs in diethyl ether increases as the hardness of the ethylating agent increases, and in the case of the same ethyl halide, the selectivity increases from the solvent-separated ion pairs to the contact ion pairs. The spectral data obtained and the data on changes in the regioselectivity do not allow one to believe that the contact ion pairs of the lithium derivative in ether exhibit the intramolecular coordination of the lithium cation to the methoxy group, which might lead to the allenylic structure of contact ion pairs of this derivative. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2043–2051, November, 1997.     

Anion influence on extraction and transport of amino acid methyl esters by functionalised calix[4]arene

The liquid–liquid extraction of a series of amino acid methyl esters has been carried out with functionalised calix[4]arene (5,11,17,23-tetrakis(N-methylpiperazino)-25,26,27,28-tetrahydroxycalix[4]arene) from an aqueous phase into a chloroform phase as ion pairs in the presence of picrate ion or tropaeolin 00 as counter ion in order to study the molecular recognition properties of this receptor. The active transport assisted by pH gradient of amino acids as ion pairs through liquid membrane employing the functionalised calix[4]arene as carrier has been investigated. The results showed that the receptor exhibits good extractability towards amino acids and it can also act as carrier through liquid membrane aiming to the separation of amino acids. It was highlighted that the anion nature used as counter ion, the structure of calix[4]arene, and the structure of amino acids are responsible for the experimental results obtained. High yields in both amino acids extraction and transport were obtained for picrate ion used as counter ion.     

Diphosphine Capsules for Transition‐Metal Encapsulation

Self‐assembly and characterization of novel heterodimeric diphosphine capsules formed by multiple ionic interactions and composed of one tetracationic diphosphine ligand and one complementary tetraanionic calix[4]arene are described. Encapsulation of a palladium atom within a diphosphine capsule is achieved successfully by using the metal complex of the tetracationic diphosphine ligand for the assembly process. In this templated approach to metal encapsulation, the transition‐metal complex is an integrated part of the capsule with the transition metal located inside the capsule and is not involved in the assembly process. We present two approaches for capsule assembly by mixing solutions of the precharged building blocks in methanol and mixing solutions of the neutral building blocks in methanol. The scope of the diphosphine capsules and the metallodiphosphine capsules is easily extended by applying tetracationic diphosphine ligands with different backbones (ethylene, diphenyl ether, and xanthene) and cationic binding motifs (p‐C₆H₄‐CH₂‐ammonium, m‐C₆H₄‐ammonium, and m‐C₆H₄‐guanidinium). These tetracationic building blocks with different flexibilities and shapes readily associate into capsules with the proper capsular structure, as is indicated by ¹H NMR spectroscopy, 1D NOESY, ESI‐MS, and modeling studies.     

Structural alteration of hybrid supramolecular capsule induced by guest encapsulation

Heterofunctionalized C(2v) symmetrical cavitand 1 with 4-pyridylethynyl and 3-carbamoylphenyl groups in alternating arrangement was designed and synthesized. A 1:1 mixture of the cavitand 1 and a cis-coordinated palladium(II) or platinum(II) complex self-assembled into a hybrid supramolecular capsule via both metal-ligand coordination bonds and hydrogen bonds. Formation of the capsular assembly was confirmed by NMR spectroscopy and mass spectrometry. The hybrid capsule encapsulated the appropriate guest, the molecular sizes of which fit the size of the capsular cavity. Structural alteration of the hybrid capsule was induced by the guest encapsulation. A C(2h) structure for the encapsulation complex was assigned by 2D NMR spectra analysis. Thermodynamic and kinetic properties of the guest encapsulation were investigated. The kinetics of in/out guest exchange was strongly influenced by hydrogen bonding in the hybrid capsule.     

Chiral Encapsulation by Directional Interactions

The complexation of chiral guests in the cavity of dimeric self‐assembled chiral capsule 1 ₂ was studied by using NMR spectroscopy and X‐ray crystallography. Capsule 1 ₂ has walls composed of amino acid backbones forming numerous directional binding sites that are arranged in a chiral manner. The polar character of the interior dictates the encapsulation preferences towards hydrophilic guests and the ability of the capsule to extract guests from water into an organic phase. Chiral discrimination towards hydroxy acids was evaluated by using association constants and competition experiments, and moderate de values were observed (up to 59 %). Complexes with one or two guest molecules in the cavity were formed. For 1:1 complexes, solvent molecules are coencapsulated; this influences guest dynamics and makes the chiral recognition solvent dependent. Reversal of the preferences can be induced by coencapsulation of a nonchiral solvent in the chiral internal environment. For complexes with two guests, filling of the capsule’s internal space can be very effective and packing coefficients of up to 70 % can be reached. The X‐ray crystal structure of complex 1 ₂?((S) ‐6 )₂ with well‐resolved guest molecules reveals a recognition motif that is based on an extensive system of hydrogen bonds. The optimal arrangement of interactions with the alternating positively and negatively charged groups of the capsule’s walls is fulfilled by the guest carboxylic groups acting simultaneously as hydrogen‐bond donors and acceptors. An additional guest molecule interacting externally with the capsule reveals a possible entrance mechanism involving a polar gate. In solution, the structural features and dynamic behavior of the D₄‐symmetric homochiral capsule were analyzed by variable‐temperature NMR spectroscopy and the results were compared with those for the S₈‐symmetric heterochiral capsule.     

Highly stable self-assembly in water: ion pair driven dimerization of a guanidiniocarbonyl pyrrole carboxylate zwitterion

The synthesis of a novel water-soluble guanidiniocarbonyl pyrrole carboxylate zwitterion 2 is described, and its self-association in aqueous solutions is studied. Zwitterion 2 forms extremely stable 1:1 dimers which are held together by an extensive hydrogen bonding network in combination with two mutual interacting ion pairs as could be shown by ESI MS and X-ray structure determination. NMR dilution studies in different highly polar solvents showed that dimerization is fast on the NMR time scale with association constants ranging from an estimated 10(10) M(-1) in DMSO to a surprisingly high 170 M(-1) in water. Hence, zwitterion 2 belongs to the most efficient self-assembling systems solely on the basis of electrostatic interactions reported so far. Furthermore, an amidopyridine pyrrole carboxylic acid 10 was developed as a neutral analogue of zwitterion 2, which also dimerizes with an essentially identical hydrogen bonding pattern (according to ESI MS and X-ray structure determination) but lacking the ionic interactions. NMR binding studies demonstrated that the solely hydrogen-bonded neutral dimer of 10 is stable only in organic solvents of low polarity (K > 10(4) M(-1) in CDCl3 but <10 M(-1) in 5% DMSO in CDCl3). The comparison of both systems impressively underlines the importance of ion pair interactions for stable self-association of such H-bonded binding motifs in water.     

Selfcondensation of some γ-keto acids in sulphuric acid

A novel type of selfcondensation of some aliphatic and aromatic γ-keto acids (capable of forming γ-lactols) in concentrated sulphuric acid is described. A mechanism for the reaction is proposed, where the key intermediates are the carbonium ion formed by loss of the OH group in the γ-lactols and the α,β-unsaturated γ-lactone with an exocyclic double bond in γ-position formed by loss of one molecule of water from the γ-lactols. The proposal is supported by deuteration experiments. Structure determinations are based on IR, PMR and MS.     

五氯化磷辅助下氨基酸的自组装成肽反应研究

L-α-氨基酸和D-α-氨基酸可与五氯化磷直接发生磷酰化反应，随后自组装成多肽，但β-氨基酸不能成肽，DL-α-氨基酸成肽困难；在SOCl2存在下，α-氨基酸也不能成肽，用电喷雾质谱研究了氨基酸的自组装反应，反应过程中有五元环状的氨基酸五配位磷中间体生成，使用硅烷基保护的氨基酸，在^31PNMR中可观察到五配位磷中间体。     

N-羟基-1,6-亚甲基桥[10]轮烯-3,4-酰亚胺/乙酸钴液相催化氧化3-甲基吡啶制备烟酸

以1,6-亚甲基桥[10]轮烯-3,4-二甲酸酐为原料,与羟胺基盐酸盐经酰化和脱水反应制得N-羟基-1,6-亚甲基桥[10]轮烯-3,4-酰亚胺(2);构建了2/乙酸钴催化体系,以氧分子为氧源,乙腈为溶剂,在1 MPa氧气压力下于120℃反应20 h,氧化3-甲基吡啶制备烟酸,产率70%,其结构经~1H NMR和IR确证。     

Detection and Chiral Recognition of α‐Hydroxyl Acid through 1H and CEST NMR Spectroscopy Using a Ytterbium Macrocyclic Complex

Chiral α‐hydroxyl acids are of great importance in chemical synthesis. Current methods for recognizing their chirality by ¹H NMR are limited by their small chemical shift differences and intrinsic solubility problem in organic solvents. Herein, we developed three YbDO3A(ala)₃ derivatives to recognize four different commercially available chiral α‐hydroxyl acids in aqueous solution through ¹H NMR and chemical exchange saturation transfer (CEST) spectroscopy. The shift difference between chiral α‐hydroxyl acid observed by proton and CEST NMR ranged from 15–40 and 20–40 ppm, respectively. Our work demonstrates for first time, that even one chiral center on the side‐arm chain of cyclen could set the stage for rotation of the other two non‐chiral side chains into a preferred position. This is ascribed to the lower energy state of the structure. The results show that chiral YbDO3A‐like complexes can be used to discriminate chiral α‐hydroxyl acids with a distinct signal difference.     

Determination of the structure of quinolone-γ-cyclodextrin complexes and their binding constants by means of UV–Vis and <Superscript>1</Superscript>H NMR

The host–guest inclusion complex structure and binding ability of two different quinolones with γ-cyclodextrin (γ-CD) were investigated in solution by means of UV–Vis and ¹H NMR spectroscopy. Competition of oxolinic and nalidixic acid molecules for the γ-CD cavity was evaluated by determination of association constants. Both quinolones form 1:1 inclusion complexes, their binding constants at room temperature (25 °C) under acidic and basic conditions were calculated using Benesi–Hildebrand equation. The stability of the complexes was dependent on the structure of the quinolone. In general, the weaker binding constants were observed for oxolinic acid-γ-CD complexes (1616 and 1765 M^?1) and the larger binding constants were obtained for nalidixic acid-γ-CD complexes (3760 and 3840 M^?1). ¹H NMR studies in D₂O were performed to elucidate the structure of each inclusion complex, nalidixic acid molecule penetrates more deeply into the γ-CD cavity and an intermolecular hydrogen bond is formed. Knowledge about structure and relative stability of quinolone-γ-CD complexes will be useful for future applications of these antimicrobial agents in medicinal chemistry.     

Encapsulation of small polar guests in molecular apple peels

Three aromatic oligoamides have been prepared that have alternating 1,6-diaminopyridine and 1,6-pyridinedicarboxylic acid units at the center of the sequence and two 8-amino-2-quinolinecarboxylic acid units at each extremity. The three oligomers differ in the number--3, 5, or 7-of pyridine units in the sequence. They were designed to adopt helically folded conformations in solution and in the solid state. The sequence of monomers was chosen so that the diameter of the helix is larger in the center than at each extremity, and hence they resemble helically wrapped apple peels. According to modeling studies, the pyridine units were expected to define a polar hollow within the helix that is large enough to accommodate small polar guests, whereas the quinoline units at each end of the oligomeric sequences were expected to completely cap the hollow and transform the helix cavities into a closed shell that may act as a capsule. Crystallographic studies demonstrate that the oligomers do fold into helices that define a cavity isolated from the surrounding medium in the solid state. Depending on the number of pyridine rings, one or two water molecules are bound within the capsules. The crystal structure of a capsule fragment shows that MeOH can also be hosted by the largest oligomer. Solution NMR studies confirm that binding of water also occurs in solution with the same stoichiometry as observed in the solid state. The capsules have distinct signals depending on whether they are empty, half-full, or full, and these species are in slow exchange on the NMR timescale at low temperature. Indeed, the binding and release of water molecules requires a significant conformational distortion of the helix that slows down these processes. The addition of small polar molecules such as methanol, hydrazine, hydrogen peroxide, or formic acid to the largest capsule leads to the observation of new sets of NMR signals of the capsules that were assigned to complexes with these guests. However, water appears to be the preferred guest.     

Synthesis of phthalimidines. Acid-catalyzed cyclodehydration versus cyclodeamination of γ-hydroxyamides obtained from dilithio-N-substituted benzamides and ketones

An earlier method of preparation of γ-hydroxyamides from N-substituted benzamides and ketones or aldehydes by means of n-butyllithium was improved and extended. The γ-hydroxyamides were found to undergo cyclodehydration to form γ-lactams with relatively strong acids, but cyclodeamination formed γ-lactones with relatively weak acids; the γ-lactams are substituted phthalimidines. The predominant course of cyclization was dependent also on the structure of the γ-hydroxyamide. Certain γ-hydroxyamides afforded phthalimidines with cold, concentrated sulfuric acid whereas certain others yielded γ-lactones with this acid. The latter γ-hydroxyamides, however, produced phthalimidines with the stronger acid, perchloric acid. The cyclodehydration reaction furnished a convenient and, apparently, quite general method for the synthesis of 2,3,3-trisubstituted or 2,3-disubstituted phthalimidines. Mechanisms are considered.