二元组装体集群时的高选择性杂化重组行为

多样性自组装体在混合时,通常表现出互不干扰的自分类性,能高度选择性地自分类堆积.但结构极为相似的组装子在相互混合时,会发生交互作用并表现出重组现象.文中合成和观测了具有芳香环边墙和不同酰胺侧链的C型甘脲分子夹为组装单元的混合组装行为.研究发现,此类分子在各自以单一态物质溶解于CDCl3时,能通过π-π相互作用和氢键形成二聚自组装体;若将两种具有不同酰胺侧链的C型甘脲分子夹两两混合,从理论上推测应有三种二聚自组装堆积态存在：A·A、B·B、A·B.但经1HNMR分析发现了一个有趣的现象,即当酰胺侧链上的取代基R′分别为具有C-H结构（如1和2）与PhF5基（5）的组装体两两混合时,二聚组装主要呈现出高度选择性杂化重组的A·B结构态.这种取代基控制的高选择性重组行为可能是基于π-π相互作用、N—H…O氢键,以及C—H…π等三重作用力的协同结果.     

Reassembly self-sorting triggered by heterodimerization

We report herein a five-component self-sorted system comprising molecular clips that form heterodimers 1·4 and 8·11, and homodimer 14·14 in C(6)D(5)CD(3)/CDCl(3). The three component self-sorting mixture comprising 1·1, 8·8, and 14·14 undergoes triggered reassembly self-sorting upon addition of 4·4 and 11·11.     

Substituent effects control the self-association of molecular clips in the crystalline state

We report the X-ray crystal structure of 11 molecular clips and analyze the influence of substituents (e.g., OMe, Me, and NO2) and their location on the observed crystal packing. Molecular clips 3a and 3b form tapelike structures in the crystal due to pi-pi interactions between the aromatic walls. Compounds 3d, 3eC, and 3fC form dimers driven by critical C-H...O interactions and then form tapes driven by pi-pi interactions in the crystal. These two building motifs, pi-pi and C-H...O interactions, can be used to rationalize the enantio- and diastereoselectivity observed in the X-ray crystal structures of the remaining five molecular clips. For example, the C-H...O interactions are found to dictate the formation of homochiral dimers in the structures of (+/-)-3eT and (+/-)-3fT and to control the diastereoselective formation of 6a2-6c2 dimeric motifs with internal p-dimethoxy-o-xylylene walls. Overall, the results suggest that substituent effects that induce even weak intermolecular interactions (e.g., C-H...O) can be used to reliably control crystal packing within glycoluril-based systems.     

Self-sorting: the exception or the rule?

In this paper, we pose the question of whether self-sorting in designed systems is exceptional behavior or whether it is likely to become a more general phenomenon governing molecular recognition and self-assembly. To address this question we prepared a mixture comprising two of Davis' self-assembled ionophores, Rebek's tennis ball and calixarene tetraurea capsule, Meijer's ureidopyrimidinone, Reinhoudt's calixarene bis(rosette), and two molecular clips in CDCl(3) solution and observed the behavior of this ensemble by (1)H NMR. As hypothesized, high-fidelity self-sorting behavior was observed. The influence of several key variables-temperature, concentration, equilibrium constants, and the presence of competitors-on the fidelity of self-sorting is described. These results show that self-sorting is neither the exception nor the rule. They suggest, however, that the subset of known molecular aggregates that exceed the criteria required for thermodynamic self-sorting is larger than previously appreciated and potentially quite broad.     

Molecular clips form isostructural dimeric aggregates from benzene to water

We report the synthesis and characterization of eight C-shaped methylene-bridged glycoluril dimers (1-8) bearing hydrogen-bonding amide groups on their aromatic rings. Compounds 1-6 undergo tight dimerization in CDCl3 solution (Ks > 9 x 10(5) M(-1)); binary mixtures of 1-7 form mixtures of homodimers and heterodimers in moderately selective dimerization processes (0.23 < or = Keq < or = 768; 0.253 < or = chiAB < 0.933). The high affinity formation of 1.1-6.6 is due to the commensurate nature of the geometrical constraints imposed by the pi-pi interactions and only two hydrogen bonds. The differential response of the strengths of the pi-pi interactions and H-bonds of 2.2 to changes in solvent polarity--from C6D6 to D2O--results in the formation of a solvent-independent isostructural aggregate that exhibits high affinity dimerization across the full range of solvents.     

Ureidopyrimidinones incorporating a functionalizable p-aminophenyl electron-donating group at C-6

[structure: see text] 2-Ureido-4-[1H]-pyrimidinones have been reported to dimerize via quadruple hydrogen bonding systems with dimerization constants >10(6) M(-1) in CDCl3. The dimerization constant, K(dim), is dependent on the solvent as well as the ring-substituents present, where previously alkyl (e.g., R1 = Me) and aromatic moieties (e.g., R1 = p-NO2C6H4, R1 = C6H2(OC13H27)3) have been incorporated at the C-6 position. To assess the influence of alternative, functionalizable, electron-donating groups on the dimerization motif and tautomeric distribution of isomers, the synthesis of compounds possessing aminophenyl functionality at the C-6 position has been achieved. NMR spectroscopy chemical shift analysis revealed that compound 2 (R1 = p-NH2C6H4, R2 = C6H13) existed as the 2-ureido-4-pyrimidinol dimeric DADA array in DMSO-d6, where a dimerization constant of 46 M(-1) was determined. This is the first time that a ureidopyrimidinone quadruple hydrogen bonding DADA array has been observed in pure DMSO, a highly polar solvent. The azo-derivative 5 of compound 2 was prepared which also adopted the pyrimidin-4-ol form in DMSO-d6. Compounds 7, 10 and 11 were then synthesized containing a more hydrophilic PEG unit in the lateral chain and the tautomeric distributions were determined.     

Bismuth 2,6-pyridinedicarboxylates: assembly of molecular units into coordination polymers, CO2 sorption and photoluminescence

Six inorganic-organic bismuth 2,6-pyridinedicarboxylate (pdc) compounds, [Bi(2,6-pdc)(3)]·3(dma), 1, [Bi(2,6-pdc)(3)]·3(dma)·2(H(2)O), 2, [Bi(2,6-pdc)(2)(dmf)]·(dma), 3, Bi(2,6-pdc)(2,6-pdcme)(MeOH), 4, [LiBi(2,6-pdc)(3)(H(2)O)]·2(dma), 5, and Li(5)Bi(2,6-pdc)(4)(H(2)O)(2), 6 (where dma = dimethyl ammonium cation, dmf = dimethylformamide and 2,6-pdcme = 6-methyl-oxycarbonyl pyridine 2-carboxylate) have been synthesized under solvothermal conditions and their structures determined by single crystal X-ray diffraction. Compounds 1-4 have molecular structures whereas compounds 5 and 6 form one- and three-dimensional frameworks, respectively. Compounds 1 and 2, both having similar monomeric bismuth coordination units, which are connected non-covalently into a (4,4)-connected square lattice by H-bonding interactions through dma cations. Compounds 3 and 4, both have a similar dimeric bismuth coordination unit. In 3, the dimers are connected into a one-dimensional chain by H-bonding interactions through dma cations. In the partially esterified and neutral 4, there was no such H-bonding interactions due to the absence of any dma cations. Compounds 5 and 6 have a similar monomeric bismuth coordination unit to that seen in 1 and 2. In 5, the monomers are connected through lithium cations into one-dimensional chains, which further interact non-covalently by H-bonding interactions through dma cations. In the lithium-rich 6, the monomers are connected by the lithium cations and 2,6-pdc anions into a three dimensional structure with intramolecular H-bonding interactions involving the water molecules. The non-porous 5 and 6 exhibit a reasonable amount of H(2) and CO(2) sorptions, respectively. Tb(3+)- and Eu(3+)-doped and co-doped 4 and 5 emit characteristic sensitized green/red/yellow-orange luminescence.     

The relevance of carbohydrate hydrogen-bonding cooperativity effects: a cooperative 1,2-trans-diaxial diol and amido alcohol hydrogen-bonding array as an efficient carbohydrate-phosphate binding motif in nonpolar media

Carbohydrates with suitably positioned intramolecularly hydrogen-bonded hydroxyl and amide groups have the potential to act as efficient bidentate phosphate binders by taking advantage of sigma- and/or ,sigma,pi-H-bonding cooperativity in nonpolar solvents. Donor-donor 1,2-trans-diaxial amido alcohol (1) and diol (3), in which one of the donor centres is cooperative, are very efficient carbohydrate-phosphate binding motifs. We have proven and quantified the key role of hydrogen-bonding centres indirectly involved in complexation, which serve to generate an intramolecular H-bond (six-membered cis H-bond) in 1 and 3. This motif enhances the donor nature of the H-bonding centres that are directly involved in complexation. A comparison of the thermodynamic parameters of the complexes formed between phosphate and a cooperative (1-Phos) or anti-cooperative (2-Phos) bidentate H-bonded motif of a carbohydrate has allowed us to quantify the energetic advantage of H-bonding cooperativity in CDCl3 and CDCl3/CCl4 (1:1.3) (Delta Delta G degrees=-2.2 and -2.0 kcal mol(-1), respectively). The solvent dependences of the entropy and enthalpy contributions to binding provide a valuable example of the delicate balance between entropy and enthalpy that can arise for a single process, providing effective cooperative binding in terms of Delta G degrees.     

Tubular hydrogen-bonded networks sustained by water molecules.

The design concept of functional solids relies on controlling the topology of crystal packing through exploitation of weak intermolecular forces. In the context of cyclic aggregates, the ability to anticipate the consequences of ring constituents and their stereochemistries on ring conformation is vitally important since even an apparently slight structural change effected on molecules can dramatically alter the crystal structure. We have found that solid-state structures formed by hydroxy acids with a general structure (+/-)-1 depend on steric interactions. Thus, with the exception of molecules 1b and 1e, compounds (+/-)-1a-(+/-)-1m, which possess bulky and conformationally rigid substituents, aggregate by forming tapes and sheets by alternating (+) and (-) subunits held together through carboxylic acid-to-alcohol hydrogen bonds. Homologue (+/-)-1n, with conformationally flexible substituents which allow conformational deformation, gives, by incorporation of molecules of water, an efficient hexagonal assembly which extends to the third dimension to form tubular H-bonding networks. Each puckered channel can be described as interconnected closely packed hexagons in chairlike conformations. The ethyl groups presented in (+/-)-1n gave the volume required to lock the inner hexagonal wall into a rigid structure. Attempts to obtain cyclic aggregates using small substituents, compounds (+/-)-1o-(+/-)-1q, failed. The observed supramolecular assemblies of the anhydrous compounds can be classified into one-dimensional strands and two-dimensional sheets, while three-dimensional networks are present only in the hydrated molecules (1b, 1e, and 1n). The crystal structure of the anhydrous (+/-)-1n compound confirms the important role played by water molecules in the formation of tubular structures.     

Study of inversion isomerism in some 4,5-cis-substituted-2-isoxazolidineethanols by NMR spectroscopy

A series of beta-phenyl-2-isoxazolidineethanols having cis-disposed substituents at C(4) and C(5) has been prepared by asymmetric nitrone cycloaddition reactions and their NMR spectra recorded over a wide range of temperatures. The spectra in CDCl(3) at low temperatures indicate the presence of two interconverting invertomers for some of the tri-substituted isoxazolidines. The effect of H-bonding - intramolecular in CDCl(3) and intermolecular in CD(3)OD - on the population ratio of the nitrogen invertomers has been investigated. The nitrogen inversion barriers are determined using complete line-shape analysis, and their dependence on solvent is discussed.     

A generalized supramolecular strategy for self-sorted assembly between donor and acceptor gelators

An effective supramolecular strategy for self-sorting between naphthalene-diimide (NDI) acceptor and dialkoxy-naphthalene (DAN) donor organogelators is reported. The concept is based on mismatch in the placement of the two amide functionalities in the donor and acceptor chromophores so that self-sorting ensured maximum effect of H-bonding.     

Role of the azinomycin naphthoate and central amide in sequence-dependent DNA alkylation and cytotoxicity of epoxide-bearing substructures

Studies report a strong correlation between duplex DNA alkylation and in vitro cytotoxicity for a series of azinomycin partial structures 2-6 bearing the biologically relevant epoxide. Compounds lacking the naphthoate ester (e.g., 5 and 6) were poorly reactive toward DNA and were biologically inactive, as were compounds bearing the naphthoate but lacking the terminal carboxamide (e.g., 2). Compounds were evaluated for cytotoxicity against two breast cancer cell lines. [structure: see text]     

Marked dependence on carrier-ligand bulk but not on carrier-ligand chirality of the duplex versus single-strand forms of a DNA oligonucleotide with a series of G-Pt(II)-G intrastrand cross-links modeling cisplatin-DNA adducts

The N7-Pt-N7 adjacent G,G intrastrand DNA cross-link responsible for cisplatin anticancer activity is dynamic, promotes local "melting" in long DNA, and converts many oligomer duplexes to single strands. For 5'-d(A1T2G3G4G5T6A7C8C9C10A11T12)-3' (G3), treatment of the (G3)2 duplex with five pairs of [LPt(H2O)2]2+ enantiomers (L = an asymmetric diamine) formed mixtures of LPt-G3 products (1 Pt per strand) cross-linked at G3,G4 or at G4,G5 in all cases. L chirality exerted little influence. For primary diamines L with bulk on chelate ring carbons (e.g., 1,2-diaminocyclohexane), the duplex was converted completely into single strands (G3,G4 coils and G4,G5 hairpins), exactly mirroring results for cisplatin, which lacks bulk. In sharp contrast, for secondary diamines L with bulk on chelate ring nitrogens (e.g., 2,2'-bipiperidine, Bip), unexpectedly stable duplexes having two platinated strands (even a unique G3,G4/G4,G5 heteroduplex) were formed. After enzymatic digestion of BipPt-G3 duplexes, the conformation of the relatively nondynamic G,G units was shown to be head-to-head (HH) by HPLC/mass spectrometric characterization. Because the HH conformation dominates at the G,G lesion in duplex DNA and in the BipPt-G3 duplexes, the stabilization of the duplex form only when the L nitrogen adducts possess bulk suggests that H-bonding interactions of the Pt-NH groups with the flanking DNA lead to local melting and to destabilization of oligomer duplexes. The marked dependence of adduct properties on L bulk and the minimal dependence on L chirality underscore the need for future exploration of the roles of the L periphery in affecting anticancer activity.     

Conformational analysis of Na,K-ATPase in drug-protein complexes

This review reports the effects of several drugs such as AZT (anti-AIDS), cis-Pt (antitumor), aspirin (anti-inflammatory) and vitamin C (antioxidant) on the stability and conformation of Na,K-ATPase in vitro. Drug-enzyme binding was found to be via H-bonding to the polypeptide CO and C-N groups with two binding constants K(1(AZT))=5.30 (+/-2.1)x10(5)M(-1) and K(2(AZT))=9.80 (+/-2.9)x10(3)M(-1) for AZT and one binding constant K(cis)(-Pt)=1.93 (+/-1.2)x10(4)M(-1) for cis-Pt, K(aspirin)=6.45 (+/-2.5)x10(3)M(-1) and K(ascorbate)=1.04 (+/-0.5)x10(4)M(-1) for aspirin and ascorbic acid. The enzyme secondary structure was altered with major increase of alpha-helix from 19.9% (free protein) to 22-26% and reduction of beta-sheet from 25.6% (free protein) to 17-23% upon drug complexation indicating a partial stabilization of protein conformation. The order of induced stability is AZT>cis-Pt>ascorbate>aspirin.     

Enols and thioenols of substituted cyanomonothiocarbonylmalonamides: structures, enolization vs. thioenolization, equilibria and conformations

Condensation of organic isothiocyanates with cyanoacetamides gave 24 N- and N'-substituted cyanomonothiocarbonylmalonamides in different tautomeric ratios i.e., amide-thioamides (TMA)R3NHCSCH(CN)CONR1R2 (12), thioamide-enols of amides (E) R3NHCSC(CN)=C(OH)NR1R2 (11)or amide-thioenols (TE) R3NHC(SH)=C(CN)CONR1R2 (13). The equilibrium constants (K(thioenol) =[TE]/[TMA] and K(enol) = [E]/[TMA]) in solution depend on R1, R2, R3 and the solvent. The %(E + TE)for NR1R2 increases in the order NMe2 < NHMe < NH2. The (K(thioenol) + K(enol)) in various solvents follows the order CCl4 > CDCl3 > C6D6 > THF-d8 > (CD3)2CO > CD3CN > DMF-d7 > DMSO-d6. The delta(OH) values are 16.46-17.43 and the delta(SH) values are 3.87-5.26 ppm in non polar solvents, e.g.,CDCl3 and 6.34-6.97 ppm in THF-d8 and CD3CN. An intramolecular O-H...O hydrogen bond leads to the preferred Z-configuration of the enols, and an N-H...O bond stabilizes the thioenols' preferred E-configuration with a non-bonded SH in solution. X-Ray crystallography revealed that systems with high %(E + TE) in solution mostly display the enols 11 in the solid state and systems with lower %(E +TE) in solution display structure 12. The differences in delta(OH), delta(NH), K(enol) and crystallographic data for analogous enol and thioenol systems are compared.     

Solution and solid state structure and tautomerism of azo coupled enaminone derivatives of benzoylacetone

The reaction of 4-substituted benzenediazonium tetrafluoroborates with 3-amino-1-phenylbut-2-en-1-one, 4-amino-4-phenylbut-3-en-2-one and their N-aryl derivatives 1a-1g has been used to prepare the respective azo coupling products i.e. compounds 2-5 from enaminone 1a, compounds 6-9 from enaminone 1c, compound 10 from enaminone 1d, compound 11 from enaminone 1e, compounds 12, 13 from enaminone 1f, compounds 14, 15 from enaminone 1b and compound 16 from enaminone 1g. Tautomerism of the azo coupling products prepared has been investigated in CDCl3 solutions by means of 1H, 13C and 15N NMR spectra. Crystal structures of selected products have also been investigated by means of X-ray diffraction.     

1H and 13C NMR assignments and X-ray structures for three monocyclic benzoannelated dilactam polyethers

Three monocyclic polyether dilactams, 17,18-dihydro-5H, 9H-dibenzo[e,n]1,4,10,7,13trioxadiazacyclopentadecine-6,10(7H,11H)-dione (1); 9,10,20,21-tetrahydro-5H, 12H-dibenzo[e,q]1,4,10,13,7,16tetraoxadiazacyclooctadecine-6, 13(7H,14H)-dione (2); and 6,7,9,10-tetrahydro-16H, 20H-dibenzo[h,q]1,4,7,13, 10,16tetraoxadiazacyclooctadecine-17, 21(18H,22H)-dione (3) were isolated during the synthesis of several benzoannelated cryptands. The complete assignments of the 1H and 13C NMR spectra of 1, 2 and 3 in CDCl3 were made using gCOSY, gHMBC, gHMQC, HMQC, HSQC, and NOESY 1D techniques. The ortho (H2) benzene protons show significant downfield shifts (1.16-1.43 ppm) that are consistent with an exodentate orientation for the amide carbonyl groups. The X-ray crystal structures of 1, 2 and 3 show that the carbonyl groups adopt an exodentate conformation in the solid state.     

Total syntheses of five indole alkaloids from the marine bryozoan Flustra foliacea

A general, efficient, and conceptually new approach to the total syntheses of marine-derived indole alkaloids, including (+/-)-flustramines A (1) and B (2), (+/-)-flustramides A (3) and B (4), and (+/-)-debromoflustramine B (5), is outlined. The key step in the syntheses involves the conjugated addition of an organomagnesium species derived from prenyl bromide to 2-hydroxyindolenines. Compounds 1, 2, and 5 have been synthesized in five steps with 23%, 17%, and 16% overall yield, respectively, whereas flustramides 3 and 4 have been synthesized in only four steps with 24% and 18% overall yield, respectively, on the basis of 2-hydroxyindolenines.     

Preparation of site-differentiated mixed ligand and mixed ligand/mixed metal metallacrowns

Assembly reactions that can prepare reliably regioselective metallamacrocyclic complexes have been a target in the development of metallacrowns. To this end, a series of mixed ligand and mixed ligand/mixed metal metallacrowns have been synthesized in high yield and structurally characterized. Two distinct connectivities have been observed in these types of metallacrowns. The monomeric, vacant metallacrown with mixed ligand composition [12-MC(Ni(II)N(Hshi)2(pko)2-4)] (1a) shows the connectivity pattern [-O-Ni-O-N-Ni-N-]2 while the other Ni metallacrowns, [12-MC(Ni(II)N(shi)2(pko)2-4)] (2a) and the coupled [12-MC(Ni(II)N(shi))2(pko)2-4)][12-MC(Ni(II)N(shi))3(pko)-4)] (3a) fused metallacrowns as well as the mixed metal Mn-Ni metallacrown [12-MC(Ni(II)Mn(III)N(shi)2(pko)2-4)] (4a), follow the pattern [-Ni-O-N-]4. Also, three distinct arrangements of the chelate rings around the metal ions have been observed. The syntheses are completely general, allowing for the substitution of different ligands into the metallacrown core. Compounds 1 and 4 show the 6-5-6-5-6-5-6-5 arrangement, compounds 2 and 3(1) the 6-6-5-5-6-6-5-5, and the 3(2) component the 6-6-5-5-6-5-6-5. The obtained structures can be rationalized by balancing the charge at each metal site in the metallacrown. Variable temperature magnetic susceptibility measurements show that exchange interactions for all the compounds are weak and dominantly antiferromagnetic (e.g., 2a gives an exchange coupling of J = -1.2 cm(-1) with g = 2.2). In solution, the metallacrowns are shown to be stable both to decomposition and ligand exchange.     

Hydrogen-bonding-mediated anthranilamide homoduplexes. Increasing stability through preorganization and iterative arrangement of a simple amide binding site

This paper describes the assembly of two new series of self-complementary duplexes by making use of amide units, the simplest assembling units of hydrogen bonding, as binding sites. All the new monomers possess a rigidified anthranilamide skeleton, which is stabilized by intramolecular hydrogen bonding. Amide units are iteratively introduced to one side of the preorganized skeletons to facilitate the formation of intermolecular hydrogen bonding. Compounds 2 and 3 bear two and three CONH(2) units, respectively, while 4, 6, and 7 are incorporated with two, three, and four AcNH units, respectively. For comparison, compound 5, which is similar to 4 but contains one AcNH and one CF(3)CONH unit, is also prepared. X-ray diffraction analysis of 2, 4, and 5 revealed homodimeric motifs in the solid state which are stabilized by two or more intermolecular hydrogen bonds. (1)H NMR investigations in CDCl(3) indicated that all the compounds form hydrogen-bonded homoduplexes. Duplexes 3.3, 6.6, and 7.7 are highly stable in CDCl(3), with a lower K(assoc) limit of 2.3 x 10(5) M(-1). The K(assoc) values of the three duplexes in more polar CDCl(3)/CD(3)CN (9:1, v/v) were determined with the (1)H NMR dilution method. The result opens the way for the development of new polymeric duplexes of well-ordered structures.