Synthesis of a novel uracil-2,6-diaminopyridine-lithocholic acid conjugate that self-assembles into a cyclic dimer

Synthesis and self-association studies of a uracil-2,6-diaminopyridine-lithocholic acid conjugate are described. The dimeric supramolecular structure is characterized by NMR spectroscopic, ESI-MS, and size exclusion chromatographic studies.     

A heterodifunctionalised ferrocene derivative that self-assembles in solution through complementary hydrogen-bonding interactions

A heterodifunctionalised ferrocene, containing a carboxylic acid and an amidopyridine unit, self-assembles in organic solvents through complementary hydrogen bonds.     

Self-assembly of a nucleotide-calixarene hybrid in a triangular supramolecule

The self-assembly of a thymine nucleotide-calixarene hybrid (1) in CDCl₃ as a solvent was investigated. FT-IR, ESI-MS, ¹H and DOSY-NMR spectra evidenced that compound 1 (ammonium or sodium salt) self-assembles in a triangular trimeric supramolecule by thymine-thymine hydrogen bonding. The saline form is crucial for the arrangement in the cyclic trimer as the protonation of the nucleotide phosphate groups leads the assembly toward a dimeric species.     

Developing a computational model that accurately reproduces the structural features of a dinucleoside monophosphate unit within B-DNA

The ability of a dinucleoside monophosphate to mimic the conformation of B-DNA was tested using a combination of different phosphate models (anionic, neutral, counterion), environments (gas, water), and density functionals (B3LYP, MPWB1K, M06-2X) with the 6-31G(d,p) basis set. Three sequences (5'-GX(Py)-3', where X(Py) = T, U or (Br)U) were considered, which vary in the (natural or modified) 3' pyrimidine nucleobase (X(Py)). These bases were selected due to their presence in natural DNA, structural similarity to T and/or applications in radical-initiated anti-tumour therapies. The accuracy of each of the 54 model, method and sequence combinations was judged based on the ability to reproduce key structural features of natural B-DNA, including the stacked base-base orientation and important backbone torsion angles. B3LYP yields distorted or tilted relative base-base orientations, while many computational challenges were encountered for MPWB1K. Despite wide use in computational studies of DNA, the neutral (protonated) phosphate model could not consistently predict a stacked arrangement for all sequences. In contrast, stacked base-base arrangements were obtained for all sequences with M06-2X in conjunction with both the anionic and (sodium) counterion phosphate models. However, comparison of calculated and experimental backbone conformations reveals the charge-neutralized counterion phosphate model best mimics B-DNA. Structures optimized with implicit solvent (water) are comparable to gas-phase structures, which suggests similar results should be obtained in an environment of intermediate polarity. We recommend the use of either gas-phase or water M06-2X optimizations with the counterion phosphate model to study the structure and/or reactivity of natural or modified DNA with a dinucleoside monophosphate.     

Engineering human Fhit, a diadenosine triphosphate hydrolase, into an efficient dinucleoside polyphosphate synthase

The putative human tumor suppressor gene FHIT encodes Fhit, the fragile histidine triad protein. Fhit is thought to participate in a signal transduction pathway involving dinucleoside polyphosphates. Fhit catalyzes the Mg2+-dependent hydrolysis of P1-5'-O-adenosine-P3-5'-O-adenosine triphosphate (Ap3A) to AMP and MgADP. Mutation of His96 to glycine disables Fhit as a catalyst for the hydrolysis of phosphoanhydrides such as Ap3A. However, the mutated enzyme H96G-Fhit efficiently catalyzes the synthesis of phosphoanhydride bonds in reactions of nucleoside-5'-phosphimidazolides with nucleoside di- and triphosphates. H96G-Fhit can be employed in the synthesis of a wide range of dinucleoside tri- and tetraphosphates. We here describe the use of H96G-Fhit to catalyze the synthesis of Ap3A, Ap3C, Ap3G, Ap3T, Ap3U, Cp3U, Tp3U, dAp3U, Ap4A, Ap4U, and the fluorescent Ap4etheno-C.     

Novel dinucleoside phosphotriester unit conjugated with an intercalative moiety in a stereospecific manner enhances thermal stability of an alternate-stranded triple helix

A novel phosphoramidite synthon of a dinucleoside phosphotriester unit bearing an intercalative moiety at its internucleotide linkage in a stereospecific manner was prepared and successfully incorporated into the middle portion of α-β chimeric oligoDNA. One of the resulting stereoisomeric chimera DNAs strongly enhances the thermal stability of an alternate-stranded triplex formed between the chimera and a double-stranded DNA.     

Novel imidazolium chiral ionic liquids that contain a urea functionality

Nine chiral room temperature ionic liquids (RTILs), which contain a chiral moiety and a urea functionality bonded to a imidazolium ring, have been designed and synthesized. The synthesis of these ionic liquids is concise and practical due to the commercial availability of the starting materials. These novel RTILs were readily prepared from 1-(3-aminopropyl)imidazole and amino acid ester derived isocyanates. We envision that these new chiral RTILs can serve as effective reaction media as well as chiral catalysts, which are presently being investigated in our laboratory.     

Construction of extended networks with a trimeric pyrazole synthon

A H-bonded pyrazole trimeric motif drives the self-association of bifunctional tetramethyl-4,4'-bipyrazole, yielding highly interpenetrated 3D frameworks and allowing the engineering by design of a novel supramolecular isomer.     

Photoexcitation of dinucleoside radical cations: a time-dependent density functional study

The excited states of dinucleoside phosphates (dGpdG, dApdA, dApdT, TpdA, and dGpdT) in their cationic radical states were studied with time-dependent density functional theory (TD-DFT). The ground-state geometries of all the dinucleoside phosphate cation radicals considered, in their base stacked conformation, were optimized with the B3LYP/6-31G(d) method. Further, to take into account the effect of the aqueous environment surrounding the dinucleoside phosphates, the polarized continuum model (PCM) was considered and the excitation energies were computed by using the TD-B3LYP/6-31G(d) method. From this study, we find that the first transition in all the dinucleoside molecules involves hole transfer from base to base. dG*+pdG and dApdA*+ were found to have substantially lower first transition energies than others with two different DNA bases. Higher energy transitions involve base to sugar as well as base to base hole transfer. The calculated TD-B3LYP/6-31G(d) transition energies are in good agreement with previous calculations with CASSCF/CAS-PT2 level of theory. This TD-DFT work supports the experimental findings that sugar radicals formed upon photoexcitation of G*+ in gamma-irradiated DNA and suggests an explanation for the wavelength dependence found.     

Symmetry induced supramolecular assembly of a resorcinarene trimeric molecular box

A novel trimeric resorcinarene molecular box is induced during hydrothermal synthesis by use of the 3-fold symmetric tripyridyl triazine linker molecule.     

Psychotripine: a new trimeric pyrroloindoline derivative from Psychotria pilifera

Psychotripine, a trimeric pyrroloindoline derivative with an unprecedented hendecacyclic system bearing a hexahydro-1,3,5-triazine unit, was isolated from the leaves of Psychotria pilifera. The structure was elucidated on the basis of spectroscopic and quantum theory. A possible biogenesis was also postulated.     

Highly-ordered selective self-assembly of a trimeric cationic surfactant on a mica surface

Novel trimeric cationic surfactant tri(dodecyldimethylammonioacetoxy)diethyltriamine trichloride (DTAD) has been synthesized, and its self-assembly morphology on a mineral surface has been studied. From its micelle solution, highly ordered bilayer patterns are obtained on a mica surface, whereas randomly distributed bilayer patches are formed on a silica substrate. The highly ordered bilayer patterns on mica are first caused by the matching of the special structure of DTAD headgroups with the negative charge sites on mica, which leads to the specific nucleation of DTAD on the mica surface via electrostatic interaction. Furthermore, hydrophobic interaction among the DTAD hydrocarbon chains results in the formation of the bilayer structure, and intermolecular hydrogen-bonding among the DTAD headgroups promotes the directional growth of such bilayer structures.     

Organometallic complexes that interconvert between trimeric and monomeric structures as a function of pH and their effect on human cancer and fibroblast cells

Organometallic half-sandwich complexes based on ruthenium with aminomethyl-substituted 3-hydroxy-2-pyridone ligands exist in aqueous solution as monomeric O,O′-chelate complexes or trimeric metallamacrocycles depending upon the pH. We hypothesized that administration of the compounds as stable trimers, which subsequently convert to active monomers at the reduced pH of the cancer environment, could facilitate their delivery to cancer cells without undergoing deactivation. Thus, the compounds were evaluated against cancer and fibroblast cell lines in vitro. A series of rhodium complexes, which exist mainly as monomers at neutral pH, were also studied for comparative purposes.     

A novel method for the synthesis of dinucleoside boranophosphates by a boranophosphotriester method

2'-Deoxyribonucleoside-3'-boranophosphates (nucleotide monomers), including four kinds of nucleobases, were synthesized in good yields by the use of new boranophosphorylating reagents. We have explored various kinds of condensing reagents as well as nucleophilic catalysts for the boranophosphorylation reaction with nucleosides. In the synthesis of dinucleoside boranophosphates, undesirable side reactions occurred at the O-4 of thymine and the O-6 of N2-phenylacetylguanine bases. To avoid these side reactions, additional protecting groups, benzoyl (Bz) and diphenylcarbamoyl (Dpc) groups, were introduced to thymine and guanine bases, respectively. As a result, the condensation reactions proceeded smoothly without any side reactions, and the dimers including four kinds of nucleobases were obtained in excellent yields. In the deprotection of the 5'-DMTr group, Et3SiH was found to be effective as a scavenger for the DMTr cation which caused a P-B bond cleavage. After removal of the other protecting groups by the conventional procedure, four kinds of dinucleoside boranophosphates were obtained in good yields.     

Structure and properties of a 1D supramolecule self-assembled by a copper(II) macrocycle with bicarbonate ligands

A new complex of composition [Cu(L3)(HCO^– ₃)₂] _n (1) (L3 = 3, 14-dimethyl-2, 6, 13, 17-tetraazatricyclo [14.4.0^1.18.0^7.12]docosane) has been synthesized and structurally characterized by a combination of analytical, spectroscopic, and crystallographic methods. The copper(II) coordination geometry in (1) consists of an axially elongated octahedron with four nitrogen atoms from the macrocycle and two oxygen atoms from the bicarbonate ligands. The [Cu(L3)(HCO₃ ^–)₂] unit extends its structure to form a novel 1D supramolecule (1) through intermolecular hydrogen bonding interactions between the bicarbonate ligands. Thus, the [Cu(L3)( HCO₃ ^–)₂] motif works as a metal complex synthon for the formation of the supramolecule (1).     

Transformation of Glucose into a Novel Carbasugar Amino Acid Dipeptide Isostere

The synthesis of a novel carbasugar amino acid (15), starting from D‐glucose and using the Ferrier rearrangement as a key step, is reported. Compound 15 is implemented as dipeptide isostere in the synthesis of a Leu‐enkephalin analog.     

A unique borotungstate containing a discrete Keggin-type anion and a trimeric saturated Keggin-type anion

A unique hybrid borotungstate, [Cu(En)(Phen)(H₂O)]₄[α-BW₁₂O₄₀]{[Cu(En)(Phen)]₂[Cu(En)₂ · (H₂O)]₂[Cu(En)(Phen)(H₂O)]₂[α-BW₁₂O₄₀]₃]} sd 10H₂O (I) (Phen = 1,10-phenanthroline, En = ethylenediamine), has been hydrothermally synthesized and characterized by elemental analyses, IR, and UV spectra, powder X-ray diffraction, thermogravimetric analysis, X-ray photoelectron spectroscopy, and singlecrystal X-ray diffraction analysis. X-ray crystallography shows that I contains a discrete saturated Keggin-type [BW₁₂O₄₀]⁵⁻ polyoxoanion and a rare trimeric saturated Keggin-type polyoxoanion {[Cu(En)(Phen)]₂[Cu(En)₂(H₂O)]₂[Cu(En)(Phen)(H₂O)]₂[α-BW₁₂O₄₀]₃]}³⁻. It is noteworthy that I represents the first example of borotungstate containing four saturated Keggin-type units in one molecule.