Intramolecular Hydrogen-bonded Systems Research Articles

Spectroscopic, Spectrometric and Computational Studies of New Lasalocid Derivatives and Their Complexes with Selected Metal Cations.

A series of five esters of lasalocid with neopentyl alcohol (LasNeo), geraniol (LasGeran), 2-ethylhexanol (LasEtHex), eicosanol (LasEico) and vanillyl alcohol (LasVanil) were synthesized and studied by NMR, FT-IR and ESI-MS. Then, their complexes with lithium, sodium and potassium cations were obtained and examined using FT-IR. The analysis of the products confirmed the synthesis of new esters with good yields. The newly obtained compounds, as well as their complexes with monovalent cations, were proved to be stabilized by a strong system of intramolecular hydrogen bonds. The PM6 semiempirical calculations provided information on the heat of formation (HOF) and permitted the making of visual representations of the structures of the newly synthesized esters and their complexes with the investigated cations. All the computational outcomes were consistent with the spectroscopic data.

EXO-LIGAND COMPLEXES OF DIETHYLENTRIAMINE-PENTAACETATOGERMANATIC(IV) ACID

The synthesis of complexes based on diethylenetriaminepenta-acetategermanate(IV) acid and a number of exo-ligands was carried out. Their composition, thermal stability, method of coordination of diethylenetriaminepentaacetic acid (H5Dtpa) and protonation of exo-ligands (isoniazid Ind, diphenylguanidine Dphg, piracetam Pam, imidazole Im, cytosine Ctz, 1,10-phenanthroline Phen, 2,2´-bipyridine Bipy), were established. The structural scheme and molecular formula of the obtained compounds were proposed (HL)[Ge(OH)(HDtpa)]·nH2O, де L = Ind, n = 0 (1), Dphg, n = 8 (2), Pam, n = 4 (3), Im, n = 2 (4), Ctz, n = 2 (5), Phen, n = 5 (6), Bipy, n = 4 (7). Based on the elemental analysis of the synthesis products 1–7, it was determined that they exhibit a molar ratio of Ge:N = 1:6 (1, 2, 5), Ge:N = 1:5 (3, 4, 6, 7), therefore, Ge:Dtpa:Ind (Dphg, Pam, Im, Ctz, Phen, Bipy) = 1:1:1. The thermal decomposition of complexes 2–7 begins with an endothermic effect in the temperature range of 80–180 °C, during which a certain amount of crystallization water molecules is removed. The relatively high temperature of its removal is due to the formation of a broad system of intermolecular and intramolecular hydrogen bonds, which is characteristic of various metal complexonates. Thus, in the new compounds, the structure of the octahedral polyhedron of Germanium remains the same as in the original complex acid: the Ge atom is coordinated by two Nitrogen atoms and three Oxygen atoms of three Dtpa acetate groups. The coordination number of Germanium is complemented to 6 by the hydroxo-ligand. All carboxyl groups of the ligand are deprotonated, as evidenced by the presence of bands νas(COO⁻) at 1630–1690 cm⁻¹ and νs(COO⁻) at 1380–1420 cm⁻¹. The presence of Ge-N and Ge-O bonds in the synthesized complexes is confirmed by the bands of valence vibrations of these bonds in the range of 640–650 cm⁻¹ and 590–620 cm⁻¹, respectively. Particularly noteworthy is the band of deformation vibrations of the Ge-O-N group at 810–820 cm⁻¹. In complexes 1–7, a splitting of bands in the 3000 cm⁻¹ region (valence vibrations of the C-H bond) is observed, indicating that all nitrogen atoms in their molecules are coordinated or protonated. The obtained compounds are of interest as promising agents for biomedical applications.

New Hydrophilic Derivatives of Lasalocid and Their Complexes with Selected Metal Cations.

Two new esters of lasalocid, that are more hydrophilic, with glucose (LasGlu) and xylitol (LasX), have been synthesized, and their complexation of monovalent cations has been studied by various spectrometric and spectroscopic methods, such as ESI mass spectrometry, 1H, 13C NMR and FT-IR. Analyses of the results confirmed the synthesis of new esters with good yields. In order to carry out further studies, it was necessary to purify them using "flash" liquid chromatography. It was confirmed that the newly obtained molecules, as well as their complexes with lithium, sodium and potassium cations, were stabilized by a strong system of intramolecular hydrogen bonds. It was found that the hydroxyl groups of esters derived from xylitol and glucose were also involved in the complexation of cations. The results of the PM6 semiempirical calculations permitted determination of the heat of formation (HOF), and visualization of the structure of the new esters and their complexes with the cations studied. All computation results are in agreement with the spectroscopic data.

Relationship between the Crystal Structure and Tuberculostatic Activity of Some 2-Amidinothiosemicarbazone Derivatives of Pyridine.

Tuberculosis remains one of the most common diseases affecting developing countries due to difficult living conditions, the rapidly increasing resistance of M. tuberculosis strains and the small number of effective anti-tuberculosis drugs. This study concerns the relationship between molecular structure observed in a solid-state by X-ray diffraction and the 15N NMR of a group of pyridine derivatives, from which promising activity against M. tuberculosis was reported earlier. It was found that the compounds exist in two tautomeric forms: neutral and zwitterionic. The latter form forced the molecules to adopt a stable, unique, flat frame due to conjugation and the intramolecular hydrogen bond system. As the compounds exist in a zwitterionic form in the crystal state generally showing higher activity against tuberculosis, it may indicate that this geometry of molecules is the “active” form.

Intramolecular Hydrogen Bonds in Normal and Sterically Compressed o-Hydroxy Aromatic Aldehydes. Isotope Effects on Chemical Shifts and Hydrogen Bond Strength.

A number of o-hydroxy aromatic aldehydes have been synthesized to illustrate the effect of steric compression and O···O distances on the intramolecular hydrogen bond and the hydrogen bond energies. Hydrogen bond energies have been calculated using the ‘hb and out’ method using either the MP2 method or the B3LYP functional with the basis set 6-311++G(d,p). However, several compounds cannot be treated this way. Hydrogen bond energies are also determined using electron densities at bond critical points and these results are in good agreement with the results of the ‘hb and out’ model. Two-bond deuterium isotope effects on 13C chemical shifts are suggested as an experimental way to obtain information on hydrogen bond energies as they easily can be measured. Isotope effects on aldehyde proton chemical shifts have also been measured. The former show very good correlation with the hydrogen bond energies and the latter are related to short O···O distances. Short O···O distances can be obtained as the result of short C=C bond lengths, conjugative effects, and steric compression of the aldehyde group. Short O···O distances are in general related to high hydrogen bond energies in these intramolecularly hydrogen-bonded systems of resonance assisted hydrogen bond (RAHB) type.

NOTA Complexes with Copper(II) and Divalent Metal Ions: Kinetic and Thermodynamic Studies.

H3nota derivatives are among the most studied macrocyclic ligands and are widely used for metal ion binding in biology and medicine. Despite more than 40 years of chemical research on H3nota, the comprehensive study of its solution chemistry has been overlooked. Thus, the coordination behavior of H3nota with several divalent metal ions was studied in detail with respect to its application as a chelator for copper radioisotopes in medical imaging and therapy. In the solid-state structure of the free ligand in zwitterionic form, one proton is bound in the macrocyclic cavity through a strong intramolecular hydrogen-bond system supporting the high basicity of the ring amine groups (log Ka = 13.17). The high stability of the [Cu(nota)]- complex (log KML = 23.33) results in quantitative complex formation, even at pH <1.5. The ligand is moderately selective for Cu(II) over other metal ions (e.g., log KML(Zn) = 22.32 and log KML(Ni) = 19.24). This ligand forms a more stable complex with Mg(II) than with Ca(II) and forms surprisingly stable complexes with alkali-metal ions (stability order Li(I) > Na(I) > K(I)). Thus, H3nota shows high selectivity for small metal ions. The [Cu(nota)]- complex is hexacoordinated at neutral pH, and the equatorial N2O2 interaction is strengthened by complex protonation. Detailed kinetic studies showed that the Cu(II) complex is formed quickly (millisecond time scale at cCu ≈ 0.1 mM) through an out-of-cage intermediate. Conversely, conductivity measurements revealed that the Zn(II) complex is formed much more slowly than the Cu(II) complex. The Cu(II) complex has medium kinetic inertness (τ1/2 46 s; pH 0, 25 °C) and is less resistant to acid-assisted decomplexation than Cu(II) complexes with H4dota and H4teta. Surprisingly, [Cu(nota)]- decomplexation is decelerated in the presence of Zn(II) ions due to the formation of a stable dinuclear complex. In conclusion, H3nota is a good carrier of copper radionuclides because the [Cu(nota)]- complex is predominantly formed over complexes with common impurities in radiochemical formulations, Zn(II) and Ni(II), for thermodynamic and, primarily, for kinetic reasons. Furthermore, the in vivo stability of the [Cu(nota)]- complex may be increased due to the formation of dinuclear complexes when it interacts with biometals.

Vacuum Ultraviolet Photoionization of Complex Chemical Systems.

Tunable vacuum ultraviolet (VUV) radiation coupled to mass spectrometry is applied to the study of complex chemical systems. The identification of novel reactive intermediates and radicals is revealed in flame, pulsed photolysis, and pyrolysis reactors, leading to the elucidation of spectroscopy, reaction mechanisms, and kinetics. Mass-resolved threshold photoelectron photoion coincidence measurements provide unprecedented access to vibrationally resolved spectra of free radicals present in high-temperature reactors. Photoionization measurements in water clusters, nucleic acid base dimers, and their complexes with water provide signatures of proton transfer in hydrogen-bonded and π-stacked systems. Experimental and theoretical methods to track ion-molecule reactions and fragmentation pathways in intermolecular and intramolecular hydrogen-bonded systems in sugars and alcohols are described. Photoionization of laser-ablated molecules, clusters, and their reaction products inform thermodynamics and spectroscopy that are relevant to astrochemistry and catalysis. New directions in coupling VUV radiation to interrogate complex chemical systems are discussed.

Role of intramolecular hydrogen bonding in the excited-state intramolecular double proton transfer (ESIDPT) of calix[4]arene: A TDDFT study

Abstract The time-dependent density functional theory (TDDFT) method was performed to investigate the excited-state intramolecular double proton transfer (ESIDPT) reaction of calix[4]arene (C4A) and the role of the intramolecular hydrogen bonds in the ESIDPT process. The geometries of C4A in the ground state and excited states (S1, S2 and T1) were optimized. Four intramolecular hydrogen bonds formed in the C4A are strengthened or weakened in the S2 and T1 states compared to those in the ground state. Interestingly, upon excitation to the S1 state of C4A, two protons H1 and H2 transfer along the two intramolecular hydrogen bonds O1-H1···O2 and O2-H2···O3, while the other two protons do not transfer. The ESIDPT reaction breaks the primary symmetry of C4A in the ground state. The potential energy curves of proton transfer demonstrate that the ESIDPT process follows the stepwise mechanism but not the concerted mechanism. Findings indicate that intramolecular hydrogen bonding is critical to the ESIDPT reactions in intramolecular hydrogen-bonded systems.

The crystallochemical role of malonate ions in coordination polymers

All compounds that contain malonate dianions C3H2O42-(mal2-) and atoms of d- or f-metals were analyzed. Dianions mal2-in structures of examined compounds reveal 17 topological types of coordination against metal atoms. Available data shows that mal2-more often form six-membered metal cycles which is the most abundant case for all 570 crystallographic sorts of analyzed mal2-(80%). For those mal2-which form six-membered metal cycles the average observed valence angle SSS is equal to 1200. Results of regression analysis of all mal2-showed linear dependence of ∠SSS on dihedral angel (φ) between planes which go through oxygen and carbon atoms of different carboxyl groups of one anion. For the equation ∠SSS = 124.9 – 0.207φ, correlation coefficient is -0.90. Discovered that in structures of crystals when φ &lt; 600mal2-necessarily form six-membered metal cycles. Structural slackness of mal2-influence on characteristics of six-membered metal cycles formed by them. Those metal cycles usually have bath conformation. Coordination polymers with fixed type of metal atom and identical type of coordination of mal2-can have different dimension even in the absence of other linkers. This effect is evident on the example of [UO2(mal)(L)]·nH2O compounds. Reportedly [1], change of composition and structure of ligand L lead to changes in the system of intramolecular hydrogen bonds which influence on conformation of six-membered metal cycles. The change of conformation of this cycles lead to different relative spatial distribution of the three uranium atoms, connected with one mal2-. Although of the same stoichiometric composition and crystallochemical role of uranium atoms and coordinated ligand resulting polymeric groups [UO2(mal)(L)] in crystals have different dimension: 3D, 2D or 1D respectively for L – carbamide, water or dimethylacetamide. This work was supported by the base part of the government mandate of the Ministry of Education and Science of the Russian Federation.

Dynamics of Solvent Controlled ESIPT of π-Expanded Imidazole Derivatives - pH Effect

A set of π-expanded imidazole derivatives employing excited state intramolecular proton transfer (ESIPT) was designed and synthesized. The relationship between the structure and photophysical properties were thoroughly elucidated by comparing with the analogue blocked with ESIPT functionality. The compound possessing an acidic NH function as part of an intramolecular hydrogen bond system has much higher fluorescence quantum yield and Stokes shift and the π-expansion strongly influences the optical properties. The occurrence of ESIPT for imidazole tosylamide derivatives were less affected by the hydrogen-bonding ability of the solvents compared to the unprotected amine. The low pKa values for the monocation ⇌ neutral equilibrium indicate the presence of intramolecular hydrogen bonding between the amino proton and tertiary nitrogen atom.

Molecular mobility of chitosan and its interaction with montmorillonite in composite films: Dielectric spectroscopy and FTIR studies

The interaction of chitosan in the basic form with montmorillonite at different concentrations in composite films is studied with the use of dielectric spectroscopy and FTIR measurements. It is shown that the interaction of amino groups and primary hydroxyl groups of chitosan with local charges on the surfaces of montmorillonite nanoparticles is responsible for a change in the system of intramolecular and intermolecular hydrogen bonds that is typical for polysaccharides. The glass-transition temperature of chitosan in the composite systems is measured.

Inherently Chiral Iminoresorcinarenes through Regioselective Unidirectional Tautomerization

Tetraformylresorcin[4]arene is obtained in 48% yield via a chromatography-free Duff reaction. The formylated resorcinarene reacts easily with primary aliphatic and aromatic amines. The resulting imines exist exclusively in keto-enamine forms. Owing to a system of intramolecular hydrogen bonds, the reaction selectively leads to regioisomers with C4 symmetry. They possess an inherent chirality due to a propeller-like skeleton. For chiral amines, inherently chiral diastereoisomers are observed.

Theoretical Study of H/D Isotope Effects on Nuclear Magnetic Shieldings Using an ab initio Multi-Component Molecular Orbital Method

We have theoretically analyzed the nuclear quantum effect on the nuclear magnetic shieldings for the intramolecular hydrogen-bonded systems of σ-hydroxy acyl aromatic species using the gauge-including atomic orbital technique combined with our multi-component density functional theory. The effect of H/D quantum nature for geometry and nuclear magnetic shielding changes are analyzed. Our study clearly demonstrated that the geometrical changes of hydrogen-bonds induced by H/D isotope effect (called geometrical isotope effect: GIE) is the dominant factor of deuterium isotope effect on 13C chemical shift.

X-ray structure analysis of a solid solution of milbemycins A3 and A4

Milbemycins A3 and A4 are pharmaceutically and agriculturally useful macrolides isolated from Streptomyces species. The molecular structures of the title compounds were unambiguously established by a single crystal X-ray analysis of the solid solution of both compounds. The crystals present trigonal system, space group P32 with Z = 3, unit cell dimensions: a = 12.2211(4), c = 17.5372(7) Å; V = 2268.4(1) Å3, μ = 0.082 mm− 1; d = 1.183 g cm− 3. An interesting system of intramolecular hydrogen bonds and weak intermolecular CH…O type hydrogen bond was observed in the solid state.

Lanthanide(iii) complexes of aminoethyl-DO3A as PARACEST contrast agents based on decoordination of the weakly bound amino group

2-Aminoethyl DOTA analogues with unsubstituted (H3L1), monomethylated (H3L2) and dimethylated (H3L3) amino groups were prepared by improved synthetic procedures. Their solid-state structures exhibit an extensive system of intramolecular hydrogen bonds, which is probably present in solution and leads to the rather high value of the last dissociation constant. The protonation sequence of H3L1 in solution corresponds to that found in the solid state. The stability constants of the H3L1 complexes with La(3+) and Gd(3+) (20.02 and 22.23, respectively) are similar to those of DO3A and the reduction of the pK(A) value of the pendant amino group from 10.51 in the free ligand to 6.06 and 5.83 in the La(3+) and Gd(3+) complexes, respectively, points to coordination of the amino group. It was confirmed in the solid state structure of the [Yb(L1)] complex, where disorder between the SA' and TSA' isomers was found. A similar situation is expected in solution, where a fast equilibration among the isomers hampers the unambiguous determination of the isomer ratio in solution. The PARACEST effect was observed in Eu(III)-H3L1/H3L2 and Yb(III)-H3L1/H3L2 complexes, being dependent on pH in the region of 4.5-7.5 and pH-independent in more alkaline solutions. The decrease of the PARACEST effect parallels with the increasing abundance of the complex protonated species, where the pendant amino group is not coordinating. Surprisingly, a small PARACEST effect was also observed in solutions of Eu(III)/Yb(III)-H3L3 complexes, where the pendant amino group is dimethylated. The effect is detectable in a narrow pH region, where both protonated and deprotonated complex species are present in equilibrium. The data points to the new mechanism of the PARACEST effect, where the slow coordination-decoordination of the pendant amine is coupled with the fast proton exchange between the free amino group and bulk water mediates the magnetization transfer. The pH-dependence of the effect was proved to be measurable by MRI and, thus, the complexes extend the family of pH-sensitive probes.

Bright, emission tunable fluorescent dyes based on imidazole and π-expanded imidazole

A diverse set of imidazole- and π-expanded imidazole derivatives displaying excited state intramolecular proton transfer (ESIPT) was designed and synthesized. The effect of structural variation on photophysical properties was studied in detail for nine dyes. The relationship between the structure and photophysical properties was thoroughly elucidated also by comparing with analogues with blocked ESIPT functionality. All but one of the obtained compounds exhibit ESIPT, as demonstrated by large Stokes shifts (6500–15 600 cm−1). The type of π-expansion strongly influences the overall optical phenomena: while typical π-expansion preserves ESIPT activity, the direct fusion of imidazole with a naphthalene unit at positions 4 and 5 results in dyes which do not exhibit ESIPT. The compound possessing an acidic NH group as part of an intramolecular hydrogen bond system has a much higher fluorescence quantum yield and Stokes shift than its analogue bearing an OH group. The occurrence of ESIPT for tosylamide analogues is less affected by the hydrogen-bonding ability of the solvents compared to the unprotected amines. Two-photon absorption cross-sections of the selected derivatives are in the range of 5–100 GM.

Hydrogen bond assisted activation of a dinitrile towards nucleophilic attack

The possibility of tunable regioselective activation of a dinitrile towards nucleophilic attack was demonstrated. For that, a sulfo-arylhydrazone unit was introduced into malononitrile and the thus formed intramolecular hydrogen bond systems assisted specific nucleophilic attacks to the cyano moieties leading to a variety of amidines, carboxamides and iminoesters depending on the nucleophiles and conditions used.

ChemInform Abstract: An Intramolecular Hydrogen-Bonded System with Large Proton Polarizability - A Model with Regard to the Proton Pathway in Bacteriorhodopsin and Other Systems with Collective Proton Motion.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Molecular structure of basic oligomeric building units of heparan-sulfate glycosaminoglycans

This study reports in detail the results of systematic large-scale theoretical investigations of the acidic dimeric structural units (D–E, E–F, F–G, and G–H) and pentamer D–E–F–G–H (fondaparinux) of the glycosaminoglycan heparin, and their anionic forms. The geometries and energies of these oligomers have been computed using HF/6–31G(d), Becke3LYP/6–31G(d), and Becke3LYP/6–311+G(d,p) methods. The optimized geometries indicate that the most stable structure of these units in the neutral state is stabilized via a system of intramolecular hydrogen bonds. The equilibrium structure of these species changed appreciably upon dissociation. Water has a remarkable effect on the geometry of the anions studied. Because of high negative charge, the solvent effect also resulted in an appreciable energetic stabilization of biologically active anionic forms of these glycosaminoglycans. The stable energy conformations around glycosidic bonds found for dimers and pentamer investigated are compared and discussed with the available experimental X-ray structural data for the structurally related heparin-derived pentasaccharides in cocrystals with proteins.

Strongly Emitting Fluorophores Based on 1-Azaperylene Scaffold

A novel blue-emitting polycyclic aromatic system was synthesized via anion-radical coupling. Its efficient direct hydroxylation led to a phenol possessing an intramolecular hydrogen-bond system. Since the energy gap difference between the enol and keto forms of this molecule is very small, characteristic of ESIPT chromophores, bathochromically shifted fluorescence was not observed.