Geometrical Changes and Their Energies in the Formation of Donor–Acceptor Complexes

We have mapped the energy demands of the geometrical changes in donor–acceptor complexes BH₃NH₃ and AlCl₃NH₃ and in the course of their formation from their monomers. We have varied the individual geometrical parameters systematically and performed ab initio quantum chemical calculations for these structures. We investigated the energy requirements to change bond lengths and bond angles in both the monomers and complexes and the angles of torsion in the complexes. The changes of bond lengths require more energy in the monomers than in the complexes. The energies to change the acceptor bond angles in the monomers are markedly higher than in the complexes. The changes in the geometrical parameters during the complexation process are more moderate in donors than in acceptors, in agreement with prior experimental observations. The geometry versus energy variations related to the process of complexation are in agreement with the notion of relative rigidity of the donor parts and the more compliant nature of the acceptor parts as well as with the notion of competing effects in the structures of the complexes.     

Potentiometric Studies on Some α-Amino Acid-Schiff Bases and Their Manganese(III) Complexes in Dimethyl Sulfoxide–Water Mixtures at 25°C

In this study the stoichiometric protonation constants were determined for some -amino acids (glycine, L-alanine, L-methionine, L-phenylalanine, and L-threonine), the Schiff bases derived from them and 2-hydroxy-1-naphthaldehyde, along with the stoichiometric stability constants of Schiff base–Mn(III) complexes. These equilibrium constants were determined potentiometrically using a combined pH electrode system calibrated in concentration units of the hydrogen ion at 25°C, and at an ionic strength of 0.10 mol-dm^–3 NaCl in 30 and 50% dimethyl sulfoxide–water mixtures. The calculations of these constants were carried out using the PKAS and the BEST computer programs. In addition, the effects of solvent composition and structures on the protonation and the complex formation constants were investigated. The mole ratio of Mn(III) to amino acid-Schiff bases was also determined and it was found that the complexes were of the MnL₂ type.     

Spectrometric and 2D NMR Studies on the Complexation of Chlorophenols with Cyclodextrins

The formation and structure of inclusion complexes of - and-cyclodextrins with 2-chlorophenol (2CP), 3-chlorophenol (3CP),4-chlorophenol (4CP), 2,4-dichlorophenol (24DCP), 2,6-dichlorophenol(26DCP) and 3,4-dichlorophenol (34DCP) have been studied by UV-VIS and¹H NMR spectroscopy. Both cyclodextrins were found to form 1:1inclusion complexes. Bindingconstants estimated from titration studies revealed that the stability of the complexes was highly dependent on the structure and polarity of the chlorophenol and on the cyclodextrin used. In general, weaker binding constants were observed for a given chlorophenol with -cyclodextrin than with-cyclodextrin. The weakest binding constants (K_{b < 200} M^-1) were obtained for the ortho-substituted chlorophenols (2CP and 26DCP) and the largest binding constants were obtained between para-chlorophenols (4CP, 24DCP and 34DCP) and-cyclodextrin. 2D-TROESY studies of chlorophenol-cyclodextrincomplexes in D₂O provided insight into the structure of the complexes.     

Inclusion Behavior of α-Cyclodextrin with 2-Methylnaphthalene in Aqueous Solutions

By means of absorption and fluorescence spectroscopy, 2-methylnaphthalene (2MN) was found to be incorporated into the cavity of -cyclodextrin (-CD) to form a 1 : 1 inclusion complex. The 1 : 1 inclusion complex further associated with another -CD molecule, resulting in the formation of a 2 : 1 -CD-2MN inclusion complex. The equilibrium constants for the formation of the 1 : 1 and 2 : 1 inclusion complexes were estimated to be 44.6 and 376 mol-1 dm3, respectively, on the basis of a simulation of the observed 2MN fluorescence intensities. The induced circular dichroism spectra suggested that 2MN, buried within the -CD inclusion complexes, resided in a different orientation relative to the CD symmetry axis, as compared to 2MN within a -CD inclusion complex.     

Complex Formation Between Alkane-α,ω-Diols and Cyclodextrins Studied by Partial Molar Volume and Compressibility Measurements

The binding of a series of alkane-,-diols, HO(CH₂)_nOH, n = 4 to 7, to - and -cyclodextrin (CD) has been studied by measurements of partial molar volumes (PMVs) and isentropic partial molar compressibilities (PMCs) at 25°C. From the PMV and PMC data, changes in the partial molar quantities upon going from a free state in aqueous solution to a complexed state were evaluated for the diols. Negative changes in PMV and PMC were observed for complex formation with -CD, while positive values were obtained for the -CD complexes. Equilibrium constants for the different complexes, assuming the formation of 1:1 complexes, were evaluated from the PMV and/or PMC data, and were found to increase with increasing chain length of the included diol for both - and -CD complexes. The equilibrium constant for complex formation is generally higher for the -CD than for the -CD complexes.     

Synthesis of 4′-Carboxy-benzo-30-crown-10 and a Thermodynamic Study of Its Complexes with Thallium and Alkali Cations in Acetonitrile Solution

A synthetic procedure has been developed for the preparation of 4-carboxy-benzo-30-crown-10. The formation of Na+, K+, Rb+, Cs+ and Tl+ complexes with the large crown ether was investigated conductometrically in acetonitrile solution at various temperatures. The formation constants of the resulting 1:1 complexes were determined from the molar conductance-mole ratio data. It was found that the stability of the complexes vary in the order Tl+ > K+ > Rb+ > Cs+ > Na+. The data obtained in this study support the existence of a wrap around structure for the above complexes in solution. The enthalpy and entropy of complexation reactions were determined from the temperature dependence of the formation constants. In all cases, the complexes were enthalpy stabilized but entropy destabilized. The resulting TS° vs. H°plot showed a fairly good linear correlation, indicating the existence of an entropy-enthalpy compensation in the large crown complexation reactions.     

Alfaxalone: Effect of Temperature on Complexation with 2-Hydroxypropyl-β-cyclodextrin

Phase solubility analysis is used to investigate the complex formation of alfaxalone with various cyclodextrins(2-hydroxypropyl--cyclodextrine [HPBCD],-cyclodextrin [BCD] and2-hydroxypropyl--cyclodextrin [HPGCD]).The complexationwith HPBCD was studied in more detail by looking at the effect of temperature on the stability constants using phase solubility analysis. HPLC-analysis was used to measure the dissolved amount of alfaxalone.The solubility of alfaxalone increases linearly with increasing concentration of cyclodextrin, suggesting the formation of a 1 : 1 complex. For the parent BCD the complex starts precipitating out of solution when the solubilizer concentration exceeds 0.25% making the unsubstituted BCD less useful for the preparation of solutions of alfaxalone. Substituted cyclodextrins do not form insoluble complexes with alfaxalone. The complexation constant for BCD and HPBCD are comparable in magnitude, but for HPGCD, the constant is substantially lower.The effect of temperature on thecomplexation constant was also studied at elevated temperature. Increasing the temperature results in an increased S₀ (solubility without HPBCD) and a decrease in the value of the complexation constant. The net effect results in minor changes of the solubility of alfaxalone as a function of temperature. Based on regression analysis, the change in enthalpy for complex formation between alfaxalone and HPBCD is calculated as -4610 cal/mol.The results indicate that substitutedcyclodextrins are useful in the preparation of solutions of alfaxalone. Since 1 : 1 complexes are formed there is no theoretical danger for precipitation on dilution, e.g., after injection.     

Infrared matrix isolation and quantum chemical studies of the nitrous acid complexes with water

The 1:1 and 2:1 complexes between water and trans- and cis-isomers of nitrous acid have been isolated in argon matrices and studied using FTIR spectroscopy and DFT(B3LYP) calculations with a 6-311++G(2d,2p) basis set. The analysis of the experimental spectra indicate that 1:1 complexes trapped in solid argon involve very strong hydrogen bond in which acid acts as the proton donor and water as the proton acceptor. The perturbed OH stretches are −248, −228 cm⁻¹ red shifted from their free-molecules values in complexes formed by trans- and cis-HONO isomers, respectively. The calculated spectral parameters for the two complexes are in good agreement with experimental data. The calculations also predict stability of two more 1:1 weakly bound complexes formed by each isomer. In these the water acts as the proton donor and one of the two oxygen atoms of the acid as the acceptor. The experimental spectra demonstrate also formation of 2:1 complex between water and trans-HONO isomer in an argon matrix. The performed calculations indicate that the complex involves a seven-membered ring in which OH group of HONO forms very strong hydrogen bond with the oxygen atom of one water molecule and nitrogen atom acts as a weak proton acceptor for the hydrogen atom of the second water molecule of the water dimer. The observed perturbations of the OH stretch of trans-HONO (750 cm⁻¹ red shift) is much larger than that predicted by calculations (556 cm⁻¹ red shift); this difference is attributed to strong solvation effect of argon matrix on very strong hydrogen bond.     

Specific crystal structure of poly(3-hydroxybutyrate) thin films studied by infrared reflection–absorption spectroscopy

Infrared reflection–absorption (IR-RAS) and transmission spectra were measured for poly(3-hydroxybutyrate) (PHB) thin films to explore its specific crystal structure in the surface region. As IR-RAS is sensitive to the vibration mode of perpendicular orientation of the surface, differences between IR-RAS and transmission spectra indicate an orientation of the lamella structure in the surface of PHB thin films. The relative intensity of the crystalline CO stretching band in the IR-RAS spectrum is significantly weaker than that in the transmission spectrum. It may be concluded that the transient dipole moment of the CO stretching mode of the crystalline state is not oriented perpendicular but nearly parallel to the substrate surface. On the other hand, the relative intensity of the band at 3009 cm⁻¹ due to the C–H stretching mode of the C–HOC hydrogen bonding is similar between the IR-RAS and transmission spectra, suggesting that the C–H bond is oriented neither perpendicular nor parallel to the substrate surface but in an intermediate direction. Since the CO group of the C–HOC hydrogen bonding is oriented nearly parallel to the surface and its C–H group is in the intermediate direction, it is very likely that the C–HOC hydrogen bonding has a somewhat bent structure. These results are in good agreement with our previous conclusion that the C–HOC hydrogen bonding of PHB exists along the a-axis (not the b-axis) between the CH₃ group of one helix and the CO group of another helix.     

Inclusion complexes of proteins: Interaction of cyclodextrins with peptides containing aromatic amino acids studied by competitive spectrophotometry

The stability constants were measured of inclusion complexes formed from aromatic amino acids and their oligopeptides with - and-cyclodextrin, hydroxypropyl-cyclodextrin, and partially methylated-cyclodextrin. The method of competitive spectrophotometry withp-nitrophenol as a competing reagent was used, and measurements were made at pH 7.4-Cyclodextrin formed complexes of higher stability than the other hosts. The stability of complexes of oligopeptides containing L-phenylalanine was invariably higher than that of L-phenylalanine itself. A model for interaction of proteins with cyclodextrins is proposed, in which the most stable complexes are formed when the native functional form of proteins is unfolded and the nonpolar residues that are buried inside the structure are exposed to water. The complexation of the unfolded structure favors its formation; thus thermal denaturation of proteins is easier in the presence of cyclodextrins. On the other hand, this complexation prevents the intermolecular association of unfolded structures by noncovalent hydrophobic bonding between the exposed nonpolar residues; furthermore, the unfolded complexed forms may revert to the native functional form. This prevention of intermolecular association may explain the stabilizing effect of cyclodextrins on solutions of proteins: a return to the native form is achieved more easily from the complexed, unfolded form than from the unfolded, aggregated forms.Dedicated to Professor József Szejtli.     

Spectroscopic Study of Charge-Transfer Complexes of Some Dicyclohexano-Crown Ethers with Π-acceptors in Dichloromethane Solution

A spectrophotometric study was conducted on solutions of dicyclohexano-18-crown-6 and dicyclohexano-24-crown-8 with some -acceptors in methylene choride at 25 °C. The spectroscopic data indicate the formation of a charge-transfer complex. In contrast to previous results, our study shows that the Ph-O-CH2 structure is not essential for the formation of charge-transfer complexes. The formation constants (Kf) were calculated and the effect of KCl and NaCl salts on the formation and stability of the complexes is discussed.     

Diverse Modes of Solvent Inclusion in Crystalline Pseudopolymorphs of the Anthelmintic Drug Niclosamide

Single crystal X-ray structures of solvated forms of theanthelmintic drug Niclosamide reveal distinctly differentmodes of inclusion for different solvents. These modes are,respectively, cavity occupation by water molecules in 1 : 1niclosamide.H₂O, channel occupation by tetrahydrofuranmolecules in 1 : 1 niclosamide.THF, and intercalation bytetraethylene glycol molecules in 2 : 1 niclosamide.TEG. Inall three compounds the host drug molecule adopts the same,nearly planar conformation, which is maintained by anintramolecular N-H.O hydrogen bond. Host-guest recognitioninvariably involves hydrogen bonding between the drughydroxyl group and an oxygen acceptor atom of the solventmolecule. The observed modes of solvent inclusion can bereconciled with the behaviour of the crystals on heating.     

Study of the Inclusion Complexes of β-Cyclodextrin with the Sodium Salt of Trisulfonated Triphenylphosphine

The formation of inclusion complexesbetween the sodium salt of trisulfonatedtriphenylphosphine and -cyclodextrin has beeninvestigated at two temperatures by high field nuclearmagnetic resonance, electrospray mass and UV-visspectroscopies. At 268 K, titration experiments andJob's method suggest that the major species insolution is a 1 : 1 inclusion complex. The moleculargeometry of this inclusion complex was studied usingthe ROESY NMR technique complemented by molecularmodelling. All these methods converged towards thestructure attained by inserting one aromatic ring intothe hydrophobic cavity of the host from the side ofthe secondary hydroxyls. At 298 K, a higher proportionof 2 : 1 and 3 : 1 complexes induces strong alterations ofthe NMR signals, preventing an easy and reliabledetermination of association constants. Nevertheless,an apparent association constant can be determinedfrom UV-vis data by assuming a 1 : 1 equilibrium. Thegeometry of the 2 : 1 and 3 : 1 complexes is also brieflydiscussed from ROESY NMR experiments.     

Synthesis, Properties, and Crystal and Molecular Structures of New Ni(II) Complexes with Sterically Hindered Methoxy-β-iminoketones

This paper describes a procedure for the synthesis of two new volatile complexes, C₂₂H₄₀N₂NiO₄ and C₂₀H₃₆N₂NiO₄, based on sterically hindered methoxy--iminoketones. The compounds were investigated by IR spectroscopy and DTA. Full crystal-chemical analysis has been carried out. The structures are molecular. The complexes have close geometrical characteristics; the distances are Ni–O 1.826 and Ni–N 1.842 ; the O–Ni–N chelate angle is 93.2°. The complexes have an intramolecular hydrogen bond N–H...O, estimated at 2.54 (2.08) . In both structures, the packing of complexes is similar to that in nickel(II) dipivalylmethanate.     

Potentiometric and Thermodynamic Studies of 5-(4′-Sulfonylazidophenylazo)-3-phenyl-2-thioxothiazolidin-4-one and Its Metal Complexes

The proton dissociation constant of 5-(4-sulfonylazidophenylazo)-3-phenyl-2-thio- xothiazolidin-4-one (SPT) and the stability constants of its complexes with some metal ions were calculated potentiometrically in 0.1 M KCl and 40% (v/v) ethanol–water mixture. The order of stability was found to be Mn²⁺ < Co²⁺ < Ni²⁺ < Cu²⁺ < Zn²⁺. The effect of temperature on the dissociation of SPT and the stability of its complexes were studied. The corresponding thermodynamic functions were derived and discussed. The dissociation process is unspontaneous, endothermic, and entropically unfavorable. The formation of the metal complexes was found to be spontaneous, endothermic and entropically favorable.     

Rearrangement of the crystal structure during solid-phase elimination of solvate acetic acid fromN′-(5-nitrofurfurylidene)isonicotinic hydrazide monohydrate

A new crystal modification ofN-(5-nitrofurfurylidene)isonicotinic hydrazide (1) was studied by IR spectroscopy and X-ray structural analysis. The compound studied is the product of solid-phase desolvation of solvate hydrate1 of the composition [MeCOOH · 1 · H₂O]. Spontaneous elimination of solvate acetic acid results in complex overall rearrangement of the crystal structure and formation of a new system of intermolecular hydrogen bonds. The crystal hydrate of 1 : 1 composition (1c) was formed from compound1. In the crystal structure of1c molecules1 are linked in infinite chains through intermolecular C=O...W...H-N hydrogen bonds. The second hydrogen atom of the molecule of the crystallization water is involved in formation of an intermolecular O-H...N(Py) hydrogen bond with the nitrogen atom of the pyridine ring of the molecule of the adjacent chain.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2501–2505, October, 1996.     

Charge Transfer Complexes of Crown Ethers with Π-Acceptors. The Influence of NaCl and KCl on Their Stability

A spectrophotometric study was conducted on solutions of benzo-15-crown-5, dibenzo-18-crown-6 and dibenzo-24-crown-8 with the -acceptors, DDQ, and CHL in dichloromethane at room temperature. The stabilities of the resulting charge transfer complexes with the -acceptors DDQ were found to decrease in the order DB18C6>DB15C5>DB24C8 and with CHL it follows the order DB18C6>DB24C8. The addition of either NaCl or KCl affects the values of formation constants (K_c) and the order of stabilities of the charge transfer complexes. The formation constants in the absence and presence of NaCl and KCl salts were calculated and discussed.     

Naphthalene Complexation by β-Cyclodextrin: Influence of Added Short Chain Branched and Linear Alcohols

Naphthalene forms 1 : 1 complexes with -cyclodextrin (-CD)in water. The binding constant is 377 ± 35 M^-1. Addition of linear or branched alcohols causes a reduction in the apparent strength of naphthalene binding (K_app) compared to the value in the absence of additives. For example, 1% 1-pentanol reduces K_app to 184 ± 31 M^-1. Branching does not alter K_app much for a given number of carbon atoms, e.g., it is 113 ± 9 M^-1for 2-pentanol and 116 ± 8 M^-1for 3-pentanol. The exception to this is tert-butanol for which K_app is 577 ± 40 M^-1. The variation in K_app as a function of [1-pentanol] yields values for the individual equilibrium constants contributing to K_app. This reveals that a ternary complex forms involving naphthalene, the CD and 1-pentanol. The constant for formation of the ternary complex is 99 ± 29 M^-2. NaI quenching of naphthalene fluorescence indicates that the CD cavity partially protects the naphthalene excited state fromthis water phase quencher. Interestingly, the Stern–Volmer constant is lower in the presence of 1-pentanol than in its absence, although there should be more unbound (and therefore more NaI accessible) naphthalene in the former system than in the latter. These apparently contradictory results are discussed in terms of ternary complex formation.     

A spectrophotometric determination of the formation constants of the inclusion complexes ofα- andβ-cyclodextrins with the azonium and ammonium tautomers of methyl orange and methyl yellow

The color fading caused by the addition of-cyclodextrin or-cyclodextrin to an aqueous solution of a tautomeric mixture of methyl orange or methyl yellow is studied spectrophotometrically at pH 1.1 and 25.0°C. A model involving 1 : 1 stoichiometry has been used to analyze the spectrophotometric data. The addition of a cyclodextrin shifts the tautomeric mixture towards the side of the ammonium tautomer. An expression allowing the calculation of the tautomeric equilibrium constant of the inclusion complexes is derived. The formation constants of the inclusion complexes of the individual tautomers are determined. Both- and-cyclodextrins bind the ammonium tautomer stronger than the azonium tautomer. The inclusion complexes of-cyclodextrin are more stable than the corresponding ones of-cyclodextrin.     

Effect of the Formation of Inclusion Complexes With β-Cyclodextrin on the Photoisomerization and Fluorescence Properties of Aromatic Norbornadiene Derivatives

The valence photoisomerization of four aromatic norbornadiene (NBD)derivatives has been studied in ethanol and in 0.01 M -cyclodextrin(-CD) water–ethanol (v/v, 99/1) solution (WECD). Observedfirst-order rate constants are found to be of the same order of magnitude inethanol and WECD, ranging between 0.1 and 0.28 s^-1, accordingto the compound. These photoisomerization kinetic properties are attributedto the formation of inclusion complexes between NBDs and -CD. Thestoichiometry is 1 : 1, and association constants ranging between 310 and390 M^-1 have been determined fluorimetrically, usingBenesi–Hildebrand plots and a nonlinear regression method. Thestructure of the inclusion complexes is discussed on the basis of AMIsemiempirical dimension calculations and photophysical properties.