Theoretical Study of Molecular Structure,Reactivity, Lipophilicity,and Solubility of N-Hydroxyurea,N-Hydroxythiourea,and N-Hydroxysilaurea

Ab initio molecular orbital methods at the CBS-QB3 level of theory have been used to study the structure and gas-phase stability of various tautomers and rotamers of N-hydroxyurea, N-hydroxythiourea, and N-hydroxysilaurea, their anions and protonated forms. The geometries of N-hydroxyurea, N-hydroxythiourea, and N-hydroxysilaurea, their anions and cations were optimized at the Becke3LYP/CBSB7 level of theory. For all compounds studied, the amidic form is computed to be substantially more stable than the iminolic tautomer. N-Hydroxyurea and its thio and sila derivatives are computed to behave as Nacids in the gas phase. These compounds are in gas-phase weak acids with a calculated acidity of about 1425 to 1355 kJ-mol^–1. Basicities increase in the order: N-hydroxyurea < N-hydroxythiourea < N-hydroxysilaurea. The most stable protonated structures are represented by several isomers with almost equal stability. Thus, in the N-hydroxyurea, N-hydroxythiourea, and N-hydroxysilaurea, both protonation at the double bonded (C=O, C=S and Si=O) oxygen and sulfur atoms, as well as the protonation at the N(H)OH nitrogen basic center is equally probable. The experimental pK _a value (10.6) of N-hydroxyurea and the computed value (9.7) for its monohydrated complex with the specifically hydrogen-bonded water molecule to the ionizable OH group are in a good agreement. The experimental partition coefficient of N-hydroxyurea is best reproduced by the Alog P_s method. The formation of nitroxide radical in the reaction of N-hydroxyurea and its sulfur and silicon substituted derivatives with the phenol radical is an exothermic process. Thus, the \bondN(H)OH moiety of these compounds may quench the structurally related tyrosyl radicals in the active site of ribonucleotide reductase.     

Effect of metal ions (Li+, Na+, K+, Mg2+, Ca2+, Ni2+, Cu2+, and Zn2+) and water coordination on the structure and properties of L-arginine and zwitterionic L-arginine

Interactions between metal ions and amino acids are common both in solution and in the gas phase. The effect of metal ions and water on the structure of L-arginine is examined. The effects of metal ions (Li(+), Na(+), K(+), Mg(2+), Ca(2+), Ni(2+), Cu(2+), and Zn(2+)) and water on structures of Arg x M(H2O)m , m = 0, 1 complexes have been determined theoretically by employing the density functional theories (DFT) and using extended basis sets. Of the three stable complexes investigated, the relative stability of the gas-phase complexes computed with DFT methods (with the exception of K(+) systems) suggests metallic complexes of the neutral L-arginine to be the most stable species. The calculations of monohydrated systems show that even one water molecule has a profound effect on the relative stability of individual complexes. Proton dissociation enthalpies and Gibbs energies of arginine in the presence of the metal cations Li(+), Na(+), K(+), Mg(2+), Ca(2+), Ni(2+), Cu(2+), and Zn(2+) were also computed. Its gas-phase acidity considerably increases upon chelation. Of the Lewis acids investigated, the strongest affinity to arginine is exhibited by the Cu(2+) cation. The computed Gibbs energies DeltaG(o) are negative, span a rather broad energy interval (from -150 to -1500 kJ/mol), and are appreciably lowered upon hydration.     

Theoretical study of structure and properties of hexuronic acid and <Emphasis Type="SmallCaps">d</Emphasis>-glucosamine structural units of glycosaminoglycans

The Becke3LYP functional of DFT theory was used to investigate molecular structure and sodium affinity of the systems CH₃CO₂Na (1), CH₃–O–SO₃Na (2), CH₃–NH–SO₃Na (3), saccharide_1Na₂ (4), saccharide_2Na (5), saccharide_3Na₃ (6), saccharide_4Na₂ (7), and saccharide_5Na₂ (8), respectively, which are models of N- and O-sulfate glycosaminoglycans. Interaction enthalpies, entropies and Gibbs energies of the sodium-coordinated systems in the gas phase were determined with the B3LYP/6-311+G(d,p) and B3LYP/6-31+G(d) methods. The computed Gibbs energies, ΔG ^o , of model systems 1–3 are negative and span a rather broad energy interval (from −500 to −1,500 kJ mol⁻¹). Gibbs interaction energies for sodium acetate, sodium sulfate and sodium sulfamate functions of the five saccharides, systems 4–8 are always lower than those values found for the model compounds 1–3. The ionization of sodium salts of saccharides studied in gas phase is in most cases connected with considerable conformational rearrangement of the ionic species. This rearrangement causes an additional energetic stabilization of anionic species and is connected with the substantial release of entropy.     

Polylactide microspheres prepared by premix membrane emulsification—Effects of solvent removal rate

Polylactide microspheres were prepared by pre-mix membrane emulsification and subsequent extraction of solvent in a coagulation bath, and ultimately to the gas phase. The polymer was dissolved in dichloromethane and emulsified with water or water–methanol mixtures by repeated passage through a glass membrane. During and after emulsification, the droplets are exposed to a bath consisting of a mixture of water and methanol. Transfer of dichloromethane takes place into the bath and (subsequently) to the gas phase. Compared to water, the solubility of dichloromethane is increased when using water–methanol mixtures; the continuous phase can quickly dissolve a significant amount of the solvent, while transfer to the gas phase is strongly enhanced as well. This was observed experimentally and by computer simulation, using a combined model based on the Maxwell–Stefan theory for non-ideal, multi-component mass transfer.

With increasing methanol concentration, the size and span of the microspheres became smaller, and was approximately 1 μm at 30% methanol. The surface morphology of these particles was solid and smooth, whereas holes were observed in those prepared in pure water. At methanol concentrations higher than 30%, the size of the microspheres increased again. This is probably due to the swelling of the particles because of the high in-diffusion of methanol which increases the porosity of the particles. Our main conclusion is that particles of defined size and size distribution can be produced by simply adjusting the non-solvent composition of the pre-mix.     

Polymer microcapsules with a fiber-reinforced nanocomposite shell

Polymer microcapsules can be used as controlled release systems in drugs or in foods. Using layer-by-layer adsorption of common food proteins and polysaccharides, we produced a new type of microcapsule with tunable strength and permeability. The shell consists of alternating layers of pectin and whey protein fibrils, yielding a fiber-reinforced nanocomposite shell. The strength can be tightly controlled by varying the number of layers or the density and length of the fibrils in the protein layers. The mechanical stability of these microcapsules appears to be superior to that of currently available multilayer capsules. The method involves only standard unit operations and has the potential for scaling up to industrial production volumes.     

Microchannel emulsification: from computational fluid dynamics to predictive analytical model

Emulsion droplet formation was investigated in terrace-based microchannel systems that generate droplets through spontaneous Laplace pressure driven snap-off. The droplet formation mechanism was investigated through high-speed imaging and computational fluid dynamics (CFD) simulation, and we found good agreement in the overall shape of the phases during droplet formation. An analytical model was derived from the insights that were gained from the CFD simulations, which describes the droplet diameter as a function of applied pressure. The analytical model covers the influence of both process parameters and geometry of the terrace well and can be used for fast optimization and evaluation studies.     

Captopril and its dimer captopril disulfide: comparative structural and conformational studies

The crystal structures of captopril {systematic name: (2S)‐1‐[(2S)‐2‐methyl‐3‐sulfanylpropanoyl]pyrrolidine‐2‐carboxylic acid}, C₉H₁₅NO₃S, (1), and its dimer disulfide metabolite, 1,1′‐{disulfanediylbis[(2S)‐2‐methyl‐1‐oxopropane‐3,1‐diyl]}bis‐L‐proline, C₁₈H₂₈N₂O₆S₂, (2), were determined by single‐crystal X‐ray diffraction analysis. Compound (1) crystallizes in the orthorhombic space group P2₁2₁2₁, while compound (2) crystallizes in the monoclinic space group P2₁, both with one molecule per asymmetric unit. The molecular geometries of (1) and (2) are quite similar, but certain differences appear in the conformations of the five‐membered proline rings and the side chains containing the sulfhydryl group. The proline ring adopts an envelope conformation in (1), while in (2) it exists in envelope and slightly deformed half‐chair conformations. The conformation adopted by the side chain is extended in (1) and folded in (2). A minimum‐energy conformational search using Monte Carlo methods in the aqueous phase reveals that the optimized conformations of the title compounds differ from those determined crystallographically, which depend on their immediate environment. Intermolecular O—H...O and relatively weak C—H...O interactions seem to be effective in both structures and, together with S—H...O and C—H...S contacts, they create three‐dimensional networks.     

Interaction of local anaesthetics with an anionic receptor site. An ab initio SCF study on procaine, lidocaine, tocainide and mexiletine and their HCO2 complexes

The ab initio SCF method was used to study the interaction of the local anaesthetics (LAs) procaine, lidocaine, tocainide and mexiletine with anionic receptor binding sites (Asp⁻, Glu⁻) represented by formate. In the case of procaine a two-centre binding site model for the binding of LAs was constructed. This model allows optimum interactions with the cationic amine part and the polar oxygen regions of procaine. The binding of procaine base was also investigated proving that this interaction is much weaker than the interaction of charged LA with its receptor binding sites. Finally, the effect of medium was studied (employing direct reaction field theory). The solvent changes the equilibrium geometry and decreases the energy of the complexes.     

Lower Rim-Upper Rim Hydrogen-Bonded Adducts of Calix[4]arenes

An upper-rim-substituted calix[4]arene tetracarboxylic acid forms hydrogen-bonded duplexes with lower-rim-substituted tetra(4-pyridyl)- and tetra(3-pyridyl)calix[4]arenes in chloroform. The formation of these adducts was studied by extraction experiments. The association constants determined via (1)H NMR dilution experiments in CDCl(3) are 7.6 x 10(3) and 1.3 x 10(3) M(-1) for the 4-pyridyl and the 3-pyridyl derivative, respectively. IR studies in the solid state and in solution indicate that the interaction is based on hydrogen bonding and that the degree of proton transfer is negligible. VPO measurements support the formation of 1:1 adducts.     

Theoretical Study of Molecular Structure, Tautomerism, and Geometrical Isomerism of N-Methyl- and N-Phenyl-Substituted Cyclic Imidazolines, Oxazolines, and Thiazolines

The geometries of various tautomers and isomers of 2-methylamino-2-imidazoline, 2-methylamino-2-oxazoline, 2-methylamino-2-thiazoline, 2-phenylamino-2-imidazoline, 2-phenylamino-2-oxazoline, and 2-phenylamino-2-thiazoline have been studied using the Becke3LYP/6–31+G(d,p) DFT, ONIOM(Becke3LYP/6–31+G(d,p):HF/3–21G^*) and ONIOM(Becke3LYP/6–31+G(d,p):AM1) methods. The optimized geometries indicate that these molecules show a distinctly nonplanar configuration of the cyclic moieties. In the gas phase, the amino tautomers (with exception of 2-phenylamino-2-imidazoline) are computed to be more stable than the imino tautomers. Of the two possible (E and Z) isomers of methyl and phenyl derivatives of imino-oxazolidine and imino-thiazolidine species, the (Z) isomers have the lowest energy. The iminozation free energies in the gas phase were found to be 5 – 15 kJ/mol. Absolute values of K _T depend strongly on the accuracy of the method used for calculation of free energy. Solvation (using the MD simulations) causes, in most cases, a shift in tautomeric preference toward the imino species.