Pd-catalyzed inter- and intramolecular carbene transfer from group 6 metal-carbene complexes.

The use of group 6 metal-carbene complexes in inter- and intramolecular carbene transfer reactions has been studied. Thus, pentacarbonyl[(aryl)(methoxy)carbene]chromium(0) and tungsten complexes, 10, efficiently dimerize at room temperature in the presence of diverse Pd(0) and Pd(II)/Et(3)N catalysts. The effect of additives (PPh(3), AsPh(3), or SbPh(3)) on the nature and the isomeric ratio of the reaction products is negligible. The nature of the reaction products is more catalyst-dependent for metal carbenes 12 bearing alkyl groups attached to the carbene carbon. In these cases, either carbene ligand dimerization or beta-hydrogen elimination reactions are observed, depending on the catalyst. The carbene ligand dimerization reaction can be used to prepare conjugated polyenes, including those having metal moieties at both ends of the polyene system, as well as enediyne derivatives. The intramolecular carbene ligand dimerization of chromium bis-carbene complexes 28 and 30 allows the preparation of mono- and bicyclic derivatives, with ring sizes from six to nine members. For bis-carbene derivatives the beta-hydrogen elimination reaction is inhibited, provided that both metal centers are tethered by an o-xylylene group. Other alkyl complexes 32 form new mononuclear carbene complexes 37 or decompose to complex reaction mixtures. The results obtained in these reactions may be explained by transmetalation from Cr(0) to Pd(0) and the intermediacy of Pd-carbene complexes. Aminocarbene-chromium(0) complexes 15, need harsher reaction conditions to transfer the carbene ligand, and this transfer occurs only in the presence of deactivated olefins. The corresponding insertion/hydrolysis products 48 resulted in these cases. A catalytic cycle involving transmetalation from a chromacyclobutane to a palladacyclobutane is proposed to explain these results.     

Tuning organogels and mesophases with phenanthroline ligands and their copper complexes by inter- to intramolecular hydrogen bonds

A novel family of highly functionalized molecules consisting of a central 4-methyl-3,5-diacylaminobenzene platform linked in close proximity to the methyl group by two lateral aromatic rings each equipped with two long alkoxy chains has been rationally designed. The presence of amide tethers and a chelating phenanthroline fragment connected via an ester dipole formed a new class of gelating reagents and mesomorphic materials. A few of these compounds have the tendency to form macromolecule-like aggregates through noncovalent interactions in hydrocarbon solvents and were found to exhibit thermotropic cubic mesophases. In light of the X-ray molecular structure of the methoxy ligand, an infinite network maintained by intermolecular hydrogen bonds as well as by pi-pi stacking of the phenyl subunits was evidenced. FT-IR studies confirm that the common driving force for aggregation in the organogels and microsegregation in the mesophase is the occurrence of a tight intermolecular H-bonded network that does not persist in diluted solution. This situation is switched when the ligands are interlocked by a copper(I) cation. A strong intramolecular H-bond confirmed by X-ray diffraction of a single crystal for the methoxy case provides very stable complexes but inhibits the gelation of the solvents. Heating the complexes bearing long paraffin chains (n = 12 and 16) in the dried state leads to a self-organization into a columnar liquid-crystalline phase in which the columns are arranged along a 2D oblique symmetry as deduced from powder XRD experiments. In this case, the complexes with the appended counteranions self-assemble in a specific way to form columns. A striking observation is that the intramolecular hydrogen bond persists in the mesophase as it does in solution without any evidence of an extended network. As far as we are aware, these ligands and complexes are rare examples in which organogelation and thermotropic mesomorphic behavior could be observed in parallel with molecules bearing a chelating platform. Due to the synthetic availability of the 4-methyl-3,5-diacylaminobenzene core and the simplicity by which the chelating platforms can be graphed, this methodology represents a practical alternative to the production of functionalized organogelators and mesomorphic materials.     

On a semiclassical interpretation of inter- and intramolecular interactions

The semiclassical models considered here are composed by charge distributions coming from ab initio quantum-mechanical calculations on actual molecular systems. These charge distributions interact with one another according to the laws of classical electrostatics. This article describes some results of a systematic examination of the performances of this model in a variety of cases, with the aim of putting in evidence the usefulness and the limits of this inherently approximate representation of chemical interactions. Intermolecular interactions are examined first; the test cases are interactions of neutral molecules with H⁺, Li⁺, and C1^?, and the formation of H-bonded complexes. Attention is paid mainly to the energetics of the processes; each interacting molecule is considered as a unique entity and classical molecular reactivity indexes (electrostatic potential V, polarization term P) are introduced to compute the interaction energy, to interpret the details of the interaction process, and then to elaborate on less expensive computational procedures. Intramolecular interactions are considered. Attention is paid to the question of defining chemical groups starting from SCF molecular wavefunctions. The transferability and conservation degree of groups derived from localized orbitals of actual molecules is examined in detail, taking as tests their ability to reproduce charge distribution, one-electron observables, and energy. The effect of classical fields on these groups is then examined, taking into consideration external fields originated either by a point charge or by a solvent, and internal fields deriving from substitution of chemical groups. The intergroup analysis is then extended to the case of bimolecular reaction acts by considering the whole system as a supermolecule. Approximate computational procedures able to reproduce the main features of these interactions are proposed and tested. All through the article the performances of the classical models are compared with ab initio SCF calculations (mainly of low or intermediate quality).     

Carbocycles via enantioselective inter- and intramolecular iridium-catalysed allylic alkylations

Carbocycles with > 90% ee were prepared via Ir-catalysed asymmetric allylic alkylation/ring closing metathesis sequences or enantioselective Ir-catalysed intramolecular allylic alkylations.     

Reaction-phase-selective inter- and intramolecular photochemical reaction of 2-pyridone derivatives

Phase-selective photochemical reaction of 2-pyridone derivatives was examined. Irradiation of 1 in benzene mainly gave rearrangement products 2. However, intermolecular [4 + 4] photocycloaddition proceeded quantitatively in the solid state, affording photodimers 3. An effective pi-pi stacking and dipole-dipole interaction between two pyridone moieties might play important roles in an effective arrangement of 1 for photodimerization in their crystal structures. [reaction: see text]     

Prostaglandins and their cyclodextrin complexes

Generally, prostaglandins (PG) are unstable and insoluble in water, though they exhibit strong biological activities in minute amount. The most difficult problem in developing PG preparations is how to stabilize and solubilize PG without loss of their activities. We have successfully developed the pharmaceutical preparations contaning PG complexes with cyclodextrins (CD). These preparations are already on the market, namely PGE₂ ·-CD Tablet and PGE₁ ·-CD Injection. Moreover, PG and PGI₂ derivatives are now under development as a form of CD complex.     

Mechanisms of inter- and intramolecular communication in GPCRs and G proteins

This study represents the first attempt to couple, by computational experiments, the mechanisms of intramolecular and intermolecular communication concerning a guanidine nucleotide exchange factor (GEF), the thromboxane A2 receptor (TXA2R), and the cognate G protein (Gq) in its heterotrimeric GDP-bound state. Two-way pathways mediate the communication between the receptor-G protein interface and both the agonist binding site of the receptor and the nucleotide binding site of the G protein. The increase in solvent accessibility in the neighborhoods of the highly conserved E/DRY receptor motif, in response to agonist binding, is instrumental in favoring the penetration of the C-terminus of Gqalpha in between the cytosolic ends of H3, H5, and H6. The arginine of the E/DRY motif is predicted to be an important mediator of the intramolecular and intermolecular communication involving the TXA2R. The receptor-G protein interface is predicted to involve multiple regions from the receptor and the G protein alpha-subunit. However, receptor contacts with the C-terminus of the alpha5-helix seem to be the major players in the receptor-catalyzed motion of the alpha-helical domain with respect to the Ras-like domain and in the formation of a nucleotide exit route in between the alphaF-helix and beta6/alpha5 loop of Gqalpha. The inferences from this study are of wide interest, as they are expected to apply to the whole rhodopsin family, given also the considerable G protein promiscuity.     

Consistent treatment of inter- and intramolecular polarization in molecular mechanics calculations

A protocol is described for the treatment of molecular polarization in force field calculations. The resulting model is consistent in that both inter- and intramolecular polarization are handled within a single scheme. An analytical formula for removing intramolecular polarization from a set of atomic multipoles for an arbitrary static structure or conformation is given. With the help of the intramolecular polarization, these permanent atomic multipoles can then be applied in modeling alternative conformations of a molecule. Equipped with this simple technique, one can derive transferable electrostatic parameters for peptides and proteins using flexible model compounds such as dipeptides. The proposed procedure is tested for its ability to describe the electrostatic potential around various configurations of the N-methylacetamide dimer. The effect of different intramolecular polarization schemes on the accuracy of a force field model of the electrostatic potential of alanine dipeptide is investigated. A group-based scheme for including direct intramolecular polarization is shown to be most successful in accounting for the conformational dependence of electrostatic potentials.     

Comparison of yttrium binaphthylamido alkyl and amide complexes for enantioselective intramolecular hydroamination

A chiral trisamido yttrium complex Y[(R)-C₂₀H₁₂(NC₅H₉)₂][NiPr₂][THF]₂·LiCl coordinated by N-cyclopentyl binaphthylamine ligand has been prepared in situ and characterised by NMR spectroscopy. It has been revealed as an efficient catalyst for intramolecular hydroamination of aminoolefins. Comparison with neutral alkyl, ate alkyl or ate tetraamido complexes coordinated by the same ligand indicated that this complex was the most efficient catalyst of the series for its both activity and enantioselectivity values.     

Effect of salt on the inter- and intramolecular hydrophobic interactions of macromolecules

The effect of salt on the structure of a low density lipoprotein (LDL) and on the reversible polymerization of bovine serum albumin (BSA) reduced with 2-mercaptoethanol was investigated by means of ultracentrifugal analysis. The chaotropic anion, e.g., SCN^– and I^–, at 5M completely disrupted the LDL structure and effectively dissociated BSA oligomers at lower concentrations. The parallelism between the anion order of these effects and that of the chaotropic effect suggested that the observed salt effects are primarily based on the disruption of hydrophobic interactions. The cation effectiveness disrupting the LDL structure followed the order of their promoting effect on the water structure, i.e., Li⁺>Na⁺>K⁺>Cs⁺. However, Cs⁺ was most effective in dissociating BSA oligomers, and this was attributed to the -complex formation with the aromatic amino acid side chains which otherwise contribute to the promotion of the intermolecular hydrophobic association.     

Contribution of inter- and intramolecular energy transfers to heat conduction in liquids

The molecular dynamics expression of heat flux, originally derived by Irving and Kirkwood [J. Chem. Phys. 18, 817 (1950)] for pairwise potentials, is generalized in this paper for systems with many-body potentials. The original formula consists of a kinetic part and a potential part, and the latter term is found in the present study to be expressible as a summation of contributions from all the many-body potentials defined in the system. The energy transfer among a set of sites for which a many-body potential is defined is discussed and evaluated by the rate of increase in the kinetic energy of each site due to the potential, and its accumulation over all the potentials in the system is shown to make up the potential part of the generalized expression. A molecular dynamics simulation for liquid n-octane was performed to demonstrate the applicability of the new expression obtained in this study to measure the heat flux and to elucidate the contributions of inter- and intramolecular potentials to heat conduction.     

Lattice self-assembly of cyclodextrin complexes and beyond

While lipids form soft, fluidic membranes (soft assembly), proteins can readily assemble into rigid, crystalline structures such as viral capsids and bacterial compartments (lattice assembly). The key difference has to do with the driving forces, where the former is driven by the weak, directionless hydrophobic effect and the latter, by a combination of relatively strong, directional intermolecular interactions. In synthetic systems, the lipid assembly has been massively replicated but the protein assembly has been rarely rivaled. Herein, we briefly review these two kinds of assemblies with special emphasis on a recently reported lattice self-assembly system of cyclodextrin complexes. The complexes arrange themselves into an in-plane, rhombic lattice that develops into lamellar, tubular, and polygonal structures depending on concentration. We will then cover the formation mechanisms, driving forces, and an application of the tubes in particle encapsulation. We hope that this short review would draw people's attention to this emerging field of lattice self-assembly.     

人参皂苷与环糊精包合物的研究进展

人参皂苷是从人参、西洋参和三七中提取的主要活性成分,其药效价值相当高,但因其在水中几乎不溶,生物利用度极低,因此极大的限制了其在临床上的应用.环糊精具有独特的性质,其"腔内疏水、腔外亲水",可以选择性的包合人参皂苷等客体分子.环糊精与人参皂苷形成包合物后可以改变客体分子的某些物理化学性能,如水溶性、稳定性以及光学性质等,以此来提高其生物利用度.     

Separation ability and stoichiometry of cyclodextrin complexes

Gas-liquid chromatography has been applied to search relations between selectivity towards isomers and stoichiometry of cyclodextrin complexes. The model tested compounds were: dimethylnaphthalenes and alpha- and beta-pinenes as constitutional isomers; cis/trans decalins, anetholes and isosafroles as diastereomers and as enantiomers (+/-)-alpha-pinenes and (+/-)-camphenes. Experimental retention data are used to confirm a simple theoretical model that allows distinguishing formation of G x CD complexes (1:1) and G x CD2 complexes (1:2). Based on the experimental data, stability constants K were evaluated. It has been found that remarkable selectivity factor alpha may appear both within the range of 1:1 stoichiometry (beta-CD complexes of decalins and of alpha- and beta-pinenes) and 1:2 stoichiometry (alpha-CD complexes with (+/-)-alpha-pinenes and (+/-)-camphenes). Occasionally selectivity arises from a different composition, when one isomer forms a 1:1 stoichiometry complex while another forms a 1:2 complex (dimethylnaphthalenes, cis/trans-anetholes and cis/trans-isosafroles).     

Modeling the interplay of inter- and intramolecular hydrogen bonding in conformational polymorphs

The predicted stability differences of the conformational polymorphs of oxalyl dihydrazide and ortho-acetamidobenzamide are unrealistically large when the modeling of intermolecular energies is solely based on the isolated-molecule charge density, neglecting charge density polarization. Ab initio calculated crystal electron densities showed qualitative differences depending on the spatial arrangement of molecules in the lattice with the greatest variations observed for polymorphs that differ in the extent of inter- and intramolecular hydrogen bonding. We show that accounting for induction dramatically alters the calculated stability order of the polymorphs and reduces their predicted stability differences to be in better agreement with experiment. Given the challenges in modeling conformational polymorphs with marked differences in hydrogen bonding geometries, we performed an extensive periodic density functional study with a range of exchange-correlation functionals using both atomic and plane wave basis sets. Although such electronic structure methods model the electrostatic and polarization contributions well, the underestimation of dispersion interactions by current exchange-correlation functionals limits their applicability. The use of an empirical dispersion-corrected density functional method consistently reduces the structural deviations between the experimental and energy minimized crystal structures and achieves plausible stability differences. Thus, we have established which types of models may give worthwhile relative energies for crystal structures and other condensed phases of flexible molecules with intra- and intermolecular hydrogen bonding capabilities, advancing the possibility of simulation studies on polymorphic pharmaceuticals.     

Macrocyclization of alpha-(alkynyloxy)silyl-alpha-diazoacetates by inter-/intramolecular

Thermally induced intra-/intermolecular [3 + 2] cycloaddition reaction sequences of alpha-(alkynyloxy)silyl-alpha-diazoacetates 1 lead to [3.3](1,4)pyrazolophanes (2)2 and higher cyclooligomers thereof [(2)n, n > 2]. In most cases, the cyclodimer was isolated by crystallization, while a complete separation of the mixture of the higher cyclooligomers was not possible. Solid state structures of cyclodimers (2b)2 and (2c)2, cyclotrimer (2b)3, and cyclotetramer (2e)4 were determined by X-ray diffraction analysis. Field-desorption mass spectra were used to characterize the cyclooligomer mixtures. The relative amounts of the cyclooligomers depend on the substitution pattern of the diazo compound. The cyclooligomerization reactions reported herein demonstrate, for the first time, the involvement of diazo functions in macrocyclization reactions via 1,3-dipolar cycloaddition.     

Synthesis of zigzag-chain and cyclic-octanuclear calcium complexes and hexanuclear bulky aryl-phosphate sodium complexes with ortho-amide groups: structural transformation involving a network of inter- and intramolecular hydrogen bonds

Three new polynuclear Ca(II)- and Na(I) phosphate complexes with two strategically oriented bulky amide groups, 2,6-(PhCONH)(2)C(6)H(3)OPO(3)H(2), were synthesized, including one with a zigzag-chain, [Ca(II)[O(3)POC(6)H(3)-2,6-(NHCOPh)(2)](H(2)O)(4)(EtOH)](n), a cyclic-octanuclear form, [Ca(II)(8)[O(3)POC(6)H(3)-2,6-(NHCOPh)(2)](8)(O=CHNMe(2))(8)(H(2)O)(12)], and a hexanuclear complex, (NHEt(3))[Na(3)[O(3)POC(6)H(3)-2,6-(NHCOPh)(2)](2)(H(2)O)(MeOH)(7)]. X-ray crystallography revealed that all have an unsymmetric ligand position due to the bulky amide groups. A dynamic transformation of the Ca(II) zigzag-chain structure to the cyclic-octanuclear complex was induced by changing coordination of DMF molecules, which caused a reorganization of the intermolecular/intramolecular hydrogen bond network.     

Synthesis of macrocyclic heteroarylenes by consecutive inter- and intramolecular cycloadditions of thiophenylene-tethered triynes

Consecutive inter- and intramolecular [2+2+2] cycloadditions of various thiophenylene-tethered triynes were comprehensively studied by using chiral Rh catalysts. When we started from 2,3- and 3,4-thiophenylene-tethered substrates, dimerization proceeded and chiral tetraheteroarylenes were obtained. In contrast, reactions of 2,5-thiophenylene-tethered substrates gave hexaheteroarylenes as trimers. When bis- and tris(2,5-thiophenylene)-tethered triynes were used, mixtures of dimers and trimers were obtained, which included macrocyclic systems that contained up to 12 aromatic rings, and their photophysical properties were measured.