Bifunctional Brønsted Base Catalyzes Direct Asymmetric Aldol Reaction of α‐Keto Amides

The first enantioselective direct cross‐aldol reaction of α‐keto amides with aldehydes, mediated by a bifunctional ureidopeptide‐based Brønsted base catalyst, is described. The appropriate combination of a tertiary amine base and an aminal, and urea hydrogen‐bond donor groups in the catalyst structure promoted the exclusive generation of the α‐keto amide enolate which reacted with either non‐enolizable or enolizable aldehydes to produce highly enantioenriched polyoxygenated aldol adducts without side‐products resulting from dehydration, α‐keto amide self‐condensation, aldehyde enolization, and isotetronic acid formation.     

Synthesis and properties of new thiourea-functionalized poly(propylene imine) dendrimers and their role as hosts for urea functionalized guests

Five generations of poly(propylene imine) dendrimers have been modified by palmityl and adamantyl endgroups via a thiourea linkage. The synthesis of the thiourea dendrimers DAB-dendr-(NHCSNHAd)(n) and DAB-dendr-(NHCSNHC(16)H(33))(n) (n = 4, 8, 16, 32, 64) proceeds smoothly via the amino-terminated DAB dendrimer and the adamantyl and palmityl isothiocyanates, respectively. The properties of the thiourea dendrimers have been studied by IR and (1)H NMR, including relaxation (T1, T2) measurements. The thiourea dendrimers are used as multivalent hosts for a number of guest molecules containing a terminal urea-glycine unit in organic solvents. The host-guest interactions have been investigated using 1D- and NOESY-NMR. These investigations show that the guest molecules bind to the dendritic host via thiourea (host)-urea (guest) hydrogen bonding, and ionic bonding between the terminal guest carboxylate moiety and the outer shell tertiary amines of the dendrimer. The ability to bind guest molecules of the adamantyl- and palmitylthiourea dendrimers has been compared with their respective urea containing dendrimer analogues, by NMR-titration, and competition experiments. Upon complexation, the thiourea dendrimer hosts show a larger downfield NH shift than the corresponding urea dendrimer hosts, indicative of stronger hydrogen bonding in the complexed state. Furthermore, microcalorimetry has been used to determine binding constants for formation of the host-guest complexes; the binding constants are typically in the order of 10(4) M(-1). Both NMR and microcalorimetric studies show that the thiourea dendrimers bind the urea containing guests with somewhat higher affinity than the corresponding urea dendrimers.     

A nonpeptidic reverse-turn scaffold stabilized by urea-based dual intramolecular hydrogen bonding

A novel nonpeptidic reverse-turn scaffold containing urea fragments that are connected by a conformationally constrained D-prolyl-cis-1,2-diaminocyclohexane (D-Pro-DACH) linker is reported. The scaffold adopts a well-defined reverse-turn conformation that is stabilized by dual intramolecular hydrogen bonding in both solution and solid states.     

Efficient control of the diastereoselectivity and regioselectivity in the singlet-oxygen ene reaction of chiral oxazolidine-substituted alkenes by a remote urea NH functionality: comparison with dimethyldioxirane and m-chloroperbenzoic acid epoxidations

The singlet-oxygen ene reaction and the epoxidation by DMD of chiral oxazolidine-substituted alkenes, equipped with a free urea NH functionality and a conformationally fixed double bond, proceed in high like diastereoselectivity (up to >95:5); also a high regioselectivity was found for the (1)O(2) ene reaction. Capping of the free NH functionality by methylation erases this like selectivity for both oxidants and significantly reduces the regioselectivity in the ene reaction. These data demonstrate effective hydrogen bonding between the remote urea NH functionality and the oxidant that favors the like attack on the C-C double bond. For (1)O(2), the hydrogen bonding in the exciplex results in preferred hydrogen abstraction from the alkyl group cis to the directing urea functionality.     

Theoretical Study of the Nontraditional Enol‐Based Photoacidity of Firefly Oxyluciferin

A theoretical analysis of the enol‐based photoacidity of oxyluciferin in water is presented. The basis for this phenomenon is found to be the hydrogen‐bonding network that involves the conjugated photobase of oxyluciferin. The hydrogen‐bonding network involving the enolate thiazole moiety is stronger than that of the benzothiazole phenolate moiety. Therefore, enolate oxyluciferin should be stabilized versus the phenolate anion. This difference in strength is attributed to the fact that the thiazole moiety has more potential hydrogen‐bond acceptors near the proton donor atom than the benzothiazole moiety. Moreover, the phenol‐based excited‐state proton transfer leads to a decrease in the hydrogen‐bond acceptor potential of the thiazole atoms. The ground‐state enol‐based acidity of oxyluciferin is also studied. This phenomenon can be explained by stabilization of the enolate anion through strengthening of a bond between water and the nitrogen atom of the thiazole ring, in an enol‐based proton‐transfer‐dependent way.     

Co-ordination behaviour of a novel bisthiourea tripodal ligand: structural, spectroscopic and electrochemical properties of a series of transition metal complexes

The synthesis of a thiourea substituted derivative of tris(pyridyl-2-methyl)amine (TPA) is reported. Two of the three pyridine rings are substituted in the 6-position with benzoylthiourea groups. These thiourea groups undergo intramolecular hydrogen bonding to form six-membered rings which leaves one N-H group available to form hydrogen bonds with other molecules. This reports details how the complexation of this new ligand with transition metal ions yields complexes with differing geometries. Seven co-ordinate Mn(II) and Cd(II), six co-ordinate Ni(II) and five co-ordinate Co(II), Cu(II) and Zn(II) complexes have been isolated.     

Amide,urea and thiourea‐containing triphenylene derivatives: influence of H‐bonding on mesomorphic properties

The synthesis and thermotropic properties are reported for a series of hexaalkoxytriphenylenes that contain an amide, urea or thiourea group in one of their alkoxy tails. The intermolecular hydrogen bonding abilities of these molecules have a disturbing influence on the formation and stability of the columnar liquid crystalline phases. The stronger the hydrogen bonding the more the liquid crystallinity is suppressed, probably due to disturbance of the π–π stacking of the triphenylene discs. As a direct result, urea‐ and amide‐containing triphenylene derivatives are not liquid crystalline, but several thiourea derivatives show hexagonal columnar mesophases.     

Metal–Ligand Cooperation in Catalytic Intramolecular Hydroamination: A Computational Study of Iridium–Pyrazolato Cooperative Activation of Aminoalkenes

The present study comprehensively explores diverse mechanistic pathways for intramolecular hydroamination of prototype 2,2‐dimethyl‐4‐penten‐1‐amine by Cp*Ir chloropyrazole ( 1 ; Cp*=pentamethylcyclopentadienyl) in the presence of KOtBu base with the aid of density functional theory (DFT) calculations. The most accessible mechanistic pathway for catalytic turnover commences from Cp*Ir pyrazolato (Pz) substrate adduct 2 ?S, representing the catalytically competent compound and proceeds via initial electrophilic activation of the olefin C?C bond by the metal centre. It entails 1) facile and reversible anti nucleophilic amine attack on the iridium–olefin linkage; 2) Ir? C bond protonolysis via stepwise transfer of the ammonium N? H proton at the zwitterionic [Cp*IrPz–alkyl] intermediate onto the metal that is linked to turnover‐limiting, reductive, cycloamine elimination commencing from a high‐energy, metastable [Cp*IrPz–hydrido–alkyl] species; and 3) subsequent facile cycloamine liberation to regenerate the active catalyst species. The amine–iridium bound 2 a ?S likely corresponds to the catalyst resting state and the catalytic reaction is expected to proceed with a significant primary kinetic isotope. This study unveils the vital role of a supportive hydrogen‐bonded network involving suitably aligned β‐basic pyrazolato and cycloamido moieties together with an external amine molecule in facilitating metal protonation and reductive elimination. Cooperative hydrogen bonding thus appears pivotal for effective catalysis. The mechanistic scenario is consonant with catalyst performance data and furthermore accounts for the variation in performance for [Cp*IrPz] compounds featuring a β‐ or γ‐basic pyrazolato unit. As far as the route that involves amine N? H bond activation is concerned, a thus far undocumented pathway for concerted amidoalkene → cycloamine conversion through olefin protonation by the pyrazole N? H concurrent with N? C ring closure is disclosed as a favourable scenario. Although not practicable in the present system, this pathway describes a novel mechanistic variant in late transition metal–ligand bifunctional hydroamination catalysis that can perhaps be viable for tailored catalyst designs. The insights revealed herein concerning the operative mechanism and the structure–reactivity relationships will likely govern the rational design of late transition metal–ligand bifunctional catalysts and facilitate further conceptual advances in the area.     

Importance of Intermolecular Hydrogen Bonding for the Stereochemical Control of Allene–Enone (3+2) Annulations Catalyzed by a Bifunctional,Amino Acid Derived Phosphine Catalyst

The origin of stereoselectivity in the (3+2) annulation of allenes and enones catalyzed by an amino acid derived phosphine catalyst has been investigated by the use of dispersion‐corrected density functional theory. An intermolecular hydrogen bond between the intermediate zwitterion and the enone was found to be the key interaction in the two enantiomeric transition states. Additional stabilization is provided by intermolecular hydrogen‐bonding interactions between acidic positions on the catalyst backbone and the substrate. Enantioselectivity occurs because the intermolecular hydrogen bond in the transition state leading to the minor enantiomer is only possible at the expense of reactant distortion.     

Importance of Intermolecular Hydrogen Bonding for the Stereochemical Control of Allene–Enone (3+2) Annulations Catalyzed by a Bifunctional,Amino Acid Derived Phosphine Catalyst

The origin of stereoselectivity in the (3+2) annulation of allenes and enones catalyzed by an amino acid derived phosphine catalyst has been investigated by the use of dispersion‐corrected density functional theory. An intermolecular hydrogen bond between the intermediate zwitterion and the enone was found to be the key interaction in the two enantiomeric transition states. Additional stabilization is provided by intermolecular hydrogen‐bonding interactions between acidic positions on the catalyst backbone and the substrate. Enantioselectivity occurs because the intermolecular hydrogen bond in the transition state leading to the minor enantiomer is only possible at the expense of reactant distortion.     

Self‐association promoted conformational transition of (3R,4S,8R,9R)‐9‐[(3,5‐bis(trifluoromethyl)phenyl))‐thiourea](9‐deoxy)‐epi‐cinchonine

The conformational diversity of the (3R,4S,8R,9R)‐9‐[(3,5‐bis(trifluoromethyl)phenyl))‐thiourea](9‐deoxy)‐epi‐cinchonine organocatalyst is discussed. Low‐temperature NMR experiments confirmed a self‐association process, which promotes the quinoline rotation between two intramolecularly hydrogen‐bonded monomeric conformers of the catalyst. The balanced population of the coexisting monomeric and dimeric species allowed us to conduct a structural study of a rather complex conformational dynamics of the pure catalyst. The study is extended by a comparison with other members of the bifunctional amine‐thiourea organocatalyst family. Changes in the molecular structure of the catalysts influence the interplay between intra‐ and intermolecular hydrogen bonding, and yield different extent of catalyst self‐association. By assessing the conformation of the individual states, we established the thermodynamic model of a self‐association promoted conformational transition. Copyright © 2009 John Wiley & Sons, Ltd.     

水和甲醇混合溶剂氢键相互作用及对高分子链溶解能力的理论研究

用密度泛函理论对水和甲醇混合溶剂体系的氢键结构进行了详细研究.通过构象和频率分析发现在水团簇中五聚体和六聚体环状结构最为稳定,同时发现一个全新的特征,即甲醇分子能与水五聚体和六聚体形成双氢键.根据各相互作用的稳定化能,分析了水和甲醇混合溶剂对PNIPAM溶解能力的影响,并对实验现象给予了合理解释.     

Synthesis of pyrrole urea and pyrrole carbonylurea derivatives

A series of urea and carbonylurea distamycin analogs whereby the linker has two NH groups for hydrogen bonding with base pairs of DNA were synthesized. The urea and carbonylurea derivatives are prepared from the in situ generation of pyrrole isocyanate (prepared from compound 3) and acyl isocyanate (compound 9), followed by the reaction with an amine. The synthetic feasibility for the further transformations of the pyrrole urea and pyrrole carbonylurea derivatives was also addressed. The binding abilities of these molecules to calf thymus DNA were evaluated by DNA melting temperature (T_m) analysis.     

Transition state docking: a probe for noncovalent catalysis in biological systems. Application to antibody-catalyzed ester hydrolysis

A strategy for pinpointing favorable noncovalent interactions between transition states and active sites of biological catalysts is described. This strategy combines high-level quantum mechanical calculations of transition state geometries with an automated docking procedure using AutoDock. By applying this methodology to antibody-catalyzed hydrolyses of aryl esters (by the 48G7, CNJ206, and 17E8 families of antibodies), varying levels of catalysis are explained in terms of specific hydrogen bonding interactions between combining site residues and transition states. Although these families of antibodies were produced in separate experiments by different researchers using related but different haptens, the mechanism of transition state stabilization appears to be highly conserved. Despite being elicited in response to anionic phosphonate haptens, the best catalysts often utilize hydrogen bond acceptors to stabilize transition states. A mutant of antibody CNJ206, designed based on this observation and predicted to be a better catalyst, is proposed. In the case of antibody 48G7, affinity maturation is shown to produce a catalyst that is highly selective for one of two enantiomeric transition states from a nonselective germline precursor.     

Acyclic Janus‐AT Nucleoside Host Channels Precisely Lock Water into Single‐File Wires with Local Rotational Flexibility

Confining polar water molecules to particular geometries demands sophisticated intermolecular interactions, and not many small synthetic molecules have accomplished such a task. Herein, regioisomeric acyclic Janus‐AT nucleosides ( 1 and 2 ), with a self‐complementary fused genetic alphabet and conformationally flexible side chains, have been selectively synthesized. 1 and 2 adopt disparate base‐pair motifs from the π–π stacked hydrophobic base moieties and distinct hydrogen bond (HB) interconnections from the hydrophilic sugar residues, which in turn lead to divergent, intricate intermolecular interaction networks with different capacities to confine water molecules. Under the precise control of the host framework of the N⁸‐regioisomer, separate ordered single‐file water wires can be locked through special three‐HB clamps into unique inter‐ and intra‐wire geometrical alignments. Localized dynamic synchronized rotations within the fixed framework coordinated by both the host hydroxy groups and guest water molecules were observed in a temperature‐induced reversible single‐crystal‐to‐single‐crystal transition (SCSCT).     

Metal-ligand cooperation in catalytic intramolecular hydroamination: a computational study of iridium-pyrazolato cooperative activation of aminoalkenes

The present study comprehensively explores diverse mechanistic pathways for intramolecular hydroamination of prototype 2,2-dimethyl-4-penten-1-amine by Cp*Ir chloropyrazole (1; Cp*=pentamethylcyclopentadienyl) in the presence of KOtBu base with the aid of density functional theory (DFT) calculations. The most accessible mechanistic pathway for catalytic turnover commences from Cp*Ir pyrazolato (Pz) substrate adduct 2?S, representing the catalytically competent compound and proceeds via initial electrophilic activation of the olefin C=C bond by the metal centre. It entails 1) facile and reversible anti nucleophilic amine attack on the iridium-olefin linkage; 2) Ir-C bond protonolysis via stepwise transfer of the ammonium N-H proton at the zwitterionic [Cp*IrPz-alkyl] intermediate onto the metal that is linked to turnover-limiting, reductive, cycloamine elimination commencing from a high-energy, metastable [Cp*IrPz-hydrido-alkyl] species; and 3) subsequent facile cycloamine liberation to regenerate the active catalyst species. The amine-iridium bound 2?a?S likely corresponds to the catalyst resting state and the catalytic reaction is expected to proceed with a significant primary kinetic isotope. This study unveils the vital role of a supportive hydrogen-bonded network involving suitably aligned β-basic pyrazolato and cycloamido moieties together with an external amine molecule in facilitating metal protonation and reductive elimination. Cooperative hydrogen bonding thus appears pivotal for effective catalysis. The mechanistic scenario is consonant with catalyst performance data and furthermore accounts for the variation in performance for [Cp*IrPz] compounds featuring a β- or γ-basic pyrazolato unit. As far as the route that involves amine N-H bond activation is concerned, a thus far undocumented pathway for concerted amidoalkene → cycloamine conversion through olefin protonation by the pyrazole N-H concurrent with N-C ring closure is disclosed as a favourable scenario. Although not practicable in the present system, this pathway describes a novel mechanistic variant in late transition metal-ligand bifunctional hydroamination catalysis that can perhaps be viable for tailored catalyst designs. The insights revealed herein concerning the operative mechanism and the structure-reactivity relationships will likely govern the rational design of late transition metal-ligand bifunctional catalysts and facilitate further conceptual advances in the area.     

Study of H-bond characteristics in sub- and supercritical methanol

Classical molecular dynamics simulations of various methanol phase lines near the saturation curve and the critical point have been performed to study the changes in H-bonded clusters structure at transition of methanol to supercritical state. Analysis of H-bonds statistics with combined distance-energy H-bond criterion showed that the correlations between topological characteristics of H-bonds and the mole fraction of H-bonded molecules have unique functional representation despite the phase path applied. In the present study, an attempt has been also made to evaluate the degree of hydrogen bonding by combining the DFT computations on classical MD configurations with the natural bond orbital analysis of the waves functions obtained.     

Revisiting the electronic excited-state hydrogen bonding dynamics of coumarin chromophore in alcohols: Undoubtedly strengthened not cleaved

In the present work, the electronic excited-state hydrogen bonding dynamics of coumarin chromophore in alcohols is revisited. The time-dependent density functional theory (TDDFT) method has been performed to investigate the intermolecular hydrogen bonding between Coumarin 151 (C151) and methanol (MeOH) solvent in the electronic excited state. Three types of intermolecular hydrogen bonds can be formed in the hydrogen-bonded C151–(MeOH)₃ complex. We have demonstrated again that intermolecular hydrogen bonds between C151 and methanol molecules can be significantly strengthened upon photoexcitation to the electronically excited state of C151 chromophore. Our results are consistent with the intermolecular hydrogen bond strengthening in the electronically excited state of Coumarin 102 in alcoholic solvents, which has been demonstrated for the first time by Zhao et al. At the same time, the electronic excited-state hydrogen bond cleavage mechanism of photoexcited coumarin chromophores in alcohols proposed in some other studies about the hydrogen bonding dynamics is undoubtedly excluded. Hence, we believe that the two contrary dynamic mechanisms for intermolecular hydrogen bonding in electronically excited states of coumarin chromophores in alcohols are clarified here.     

Molecular association in polyethylene glycol

Summary Existence of intra and intermolecular hydrogen bonds has been confirmed in the literature. Present reduced viscosity studies of PEG solution in urea and thiourea also confirm the view of the presence of the molecular association of PEG in water by intermolecular hydrogen bonding as well as of the existence of intramolecular hydrogen bonding in PEG molecules. The existence of intramolecular hydrogen bonding is more appreciated in the case of PEG solution in relatively smaller concentration of urea and thiourea. The presence of urea and thiourea is responsible for the breaking of hydrogen bonds which result in the change of molecular size and conformation.

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Zusammenfassung Das Auftreten von intra- und intermolekularen Wasserstoff bindungen bei Polymeren wird in der Literatur schon bestätigt. Wir zeigten an Polyäthylenglycollösungen in Wasser mit und ohne Harnstoff und Thioharnstoff, daß sich die Existenz von solchen Wasserstoffbrücken in vorliegendem Falle ebenfalls bestätigen läßt.

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With 2 figures     

Amide, urea and thiourea-containing triphenylene derivatives: influence of H-bonding on mesomorphic properties

The synthesis and thermotropic properties are reported for a series of hexaalkoxytriphenylenes that contain an amide, urea or thiourea group in one of their alkoxy tails. The intermolecular hydrogen bonding abilities of these molecules have a disturbing influence on the formation and stability of the columnar liquid crystalline phases. The stronger the hydrogen bonding the more the liquid crystallinity is suppressed, probably due to disturbance of the π-π stacking of the triphenylene discs. As a direct result, urea- and amide-containing triphenylene derivatives are not liquid crystalline, but several thiourea derivatives show hexagonal columnar mesophases.