Attachment Of Side Chains Research Articles

X-ray structures of fifty year old crystals of cholesterol iodide forms I and II

The molecular framework of steroids was firmly established from the successful X-ray analysis of cholesteryl iodide crystals over fifty years ago. At the time, this was a triumph for the rapidly developing technique of X-ray crystallography. We describe here new analyses of cholesteryl iodide using crystals of forms I and II(A) which are at least 50 years old. Comparison of these two structures reveals subtle differences in the geometry of the steroid skeleton, the attached side chain and the covalently bound iodine. The crystals of both forms occur in the same monoclinic space group, P2(1), with similar but nevertheless different unit cells, particularly in the b-axis length. As a consequence, there are subtle differences in the packing mechanisms of the two polymorphs. The two forms were originally classified by Bernal and Crowfoot, on the basis of their studies of more than 60 crystals of sterols and sterol derivatives, as "normal, type A - the common form" (corresponding to form II) and "reverse or type B" (corresponding to form I), respectively. Those crystals of form I which have survived for almost 55 years are poor X-ray diffractors at room temperature and have been analysed at liquid N temperature, diffracting well under these conditions. Form II crystals diffract well at room temperature and for this reason the crystals were not cooled. The main differences in geometry occur in the side-chain which is disordered in the room temperature form II crystals, whilst the individual ring conformations in the steroid skeleton are similar, ring A being a strained chair, ring B a 7 alpha/8 beta half-chair, ring C a symmetrical chair and D a 13 beta/14 alpha half-chair.

Water Exclusion and Enantioselectivity in Catalysis

High and dry. Enzymes perform catalyses in the interior of the protein, which is not aqueous in character. Polyethylenimine enzyme mimics with a hydrophobic core also achieve high rates by excluding water. Two different approaches to the synthesis of such artificial enzymes with chirally attached side chains are described, as well as the use of these enzymes in performing biomimetic transaminations with chiral selectivity

Why choice of contrast medium matters

Three generations of iodinized contrast media (CM) are available for use in visualization of X-ray procedures. The three types of CM are all primarily based on a tri-iodinated benzene ring structure but differ in the structure of the attached side chains. First-generation CM have an ionizing carboxyl group, meaning they dissociate into two particles in solution. Consequently, these CM have a high osmolality that has been found to result in toxic effects such as pain and heat sensation on injection and a significant risk of CM-induced nephropathy (CIN)—an important adverse event associated with CM use. Low-osmolar CM (LOCM) were developed to overcome these toxic effects and are indeed better tolerated than high-osmolar CM (HOCM). In particular, LOCM have been shown to carry a lower risk of CIN, especially in high-risk patients. However, renal failure is still one of the most severe reported adverse events associated with LOCM. Therefore, a third generation of CM has been developed that is iso-osmolar with plasma offering potential benefits with regards to tolerability compared to LOCM. Two studies in high-risk patients have shown that iodixanol is associated with a lesser effect on renal function than the LOCM iohexol. Thus, clinical data have shown that an iso-osmolar CM should be considered in patients at high risk for CIN undergoing CM-enhanced procedures.

A new approach to a vitamin D ring C/D building block from the Hajos dione, involving epoxide opening at the more substituted carbon atom

A new approach to a trans-hydrindane building block for 1α,25-dihydroxyvitamin D 3 (calcitriol) synthesis from the Hajos dione has been developed. The α,β-unsaturated carbonyl group in the Hajos dione has been protected and the carbonyl group in the five-membered ring has been used for the side chain attachment. Key steps in the six-membered ring transformation include: reduction of the carbonyl group, stereoselective epoxidation of the double bond in the allylic alcohol, opening of the epoxide at the more substituted carbon atom and regioselective deoxygenation.

Thermooxidative stability of spectra of fluorene-based copolymers

The origin of the low-energy emission of fluorene-based homo- and copolymers still remains controversial. In this work, the effect of thermal treatment on the emission properties of poly[(9,9-dihexylfluorene)-alt-co-(1,4-phenylene)] (PF6P) and its four derivatives modified by attaching different lengths of alkoxy side chains on the phenylene rings has been systematically investigated. By comparing the photoluminescence (PL) spectra of PF6P and the modified polymers, Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and PL lifetime measurements have revealed that the long wavelength emission could be attributed to the formation of fluorenone-based excimers rather than to the localized fluorenone π–π* transition, the energy transfer from fluorene segments to the fluorenone moieties, or the fluorenone defects generated by thermal oxidation during thermal treatment. Compared with PF6P, the attachment of alkoxy side chains on the phenylene rings effectively inhibits the aggregation of backbone chains, thus restrains the formation of fluorenone-based excimers and remarkably improves thermal stability of the spectra.

Dipeptide nitrile inhibitors of cathepsin K

A series of dipeptidyl nitriles as inhibitors of cathepsin K have been explored starting from lead structure 1 (Cbz–Leu–NH–CH 2–CN, IC 50 = 39 nM). Attachment of non-natural amino acid side chains in P1 and modification of the P3 subunit led to inhibitors with higher potency and improved pharmacokinetic properties.

Side-chain effects in molecular electronic devices

We discuss the effect of an abundant structural element of molecules on the transmission probabilities of molecular electronic devices. We show that an attachment of side chains to a molecular conductor may lead to zero transmission probabilities. The gaps in the transmission-probability appear approximately at the eigenvalues of the isolated side chains, provided that the corresponding eigenstates are not localized away from the molecular conductor. Simple Hückel-type calculations serve to illustrate the described effect. Furthermore, we show that complex transmission-probability curves, obtained with Kohn-Sham density-functional theory, also exhibit the described side-chain effect.

Very large electro-optic coefficients from in situ generated side-chain nonlinear optical polymers

A synthetic/processing method has been developed for achieving highly efficient nonlinear optical polymers. A maleimide-containing chromophore with large molecular nonlinearity was covalently attached onto a anthrathene-containing polymer to generate in situ a side-chain polymer via the Diels-Alder reaction. The poling and covalent side-chain attachment processes can be performed simultaneously in a solid state, resulting in high electro-optic (E-O) coefficients (r33 values up to 50pm∕V at 1310nm) and temporal stability (85% retention of the original dipole alignment after isothermal heating at 85°C for more than 500h). A very high chromophore loading level (39wt%) can be achieved by adding more chromophore into this side-chain polymer without causing any obvious phase separation. Poling of this chromophore-doped side-chain polymer (total dye content: 34wt%) showed a significantly increased E-O coefficient, from 50to110pm∕V.

Synthesis of side-chain functionalised ligands for the generation of quartet receptor arrays via self-assembly of [2×2] grid complexes

The decoration of bishydrazone compounds of types 2 and 3 by attachment of various side chains, in particular of biological nature, yields a set of functionalised ligands. Their self-assembly with zinc(II) and cobalt(II) ions into [2×2] grids provides an approach towards nanosized metallosupramolecular architectures presenting quartet receptor arrays of interest for the development of nanosized biochips.

Structural revision and total synthesis of azaspiracid-1, part 2: definition of the ABCD domain and total synthesis.

Structural revision and total synthesis of azaspiracid-1, part 2: definition of the ABCD domain and total synthesis.

A Model Route Toward the Synthesis of Conformationally Constrained Polyhydroxylated Dipeptides from Natural Carbohydrates.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Smart materials based on self-assembled hydrogen-bonded comb-shaped supramolecules.

Block copolymer self-assembly and supramolecular chemistry can be combined most naturally to prepare smart polymer nanomaterials. An attractive route is based on comb-shaped supramolecules, obtained by attaching side chains to (co)polymers by physical (non-covalent) interactions. Hydrogen bonding is a key element of our approach. It combines an ease of synthesis with other important approach-specific elements, such as hierarchical self-assembly, strongly enhanced processability, swelling, and cleaving. Functional properties discussed include anisotropic proton conductivity, switching proton conductivity, electronically conducting nanowires, polarized luminance, dielectric stacks (optical reflectivity), functional membranes, and nano objects.

Molecular Basis of Proteinuria

Molecular Basis of Proteinuria

Design, synthesis, and evaluation of azepine-based cryptophycin mimetics

Cryptophycins, depsipeptides isolated from terrestrial blue–green algae, show potent activity against a variety of tumor cell lines. Given the potential of the cryptophycins for cancer therapy, we developed a new class of non-peptide peptidomimetic, designed to replace the 16-membered macrolide ring with a 7-membered azepine ring for attachment of the cryptophycin side chains with the required spatial orientation to mimic the conformation of the relevant region of the natural product. Monte Carlo conformational analysis revealed excellent overlay of the local minimum structural model 6 and X-ray structure of (+)-cryptophycin-3 ( 5 ). Starting from this structural model, we designed and synthesized compounds (+)- 25 , (+)- 30 , and (+)- 34 as potential mimics of cryptophycins. Compounds (+)- 25 , (+)- 30 , and (+)- 34 were tested for in vitro cytotoxicity against six human cancer cell lines. Although only modest activities were observed, these results suggested that a new series of bioactive cryptophycin analogues might be available by structural modification of the central ring system of the cryptophycins.

Investigation of the Photophysical and Electrochemical Properties of Alkoxy-Substituted Arylene−Ethynylene/Arylene−Vinylene Hybrid Polymers

High-molecular-weight, soluble and thermostable alkoxy-substituted arylene−ethynylene/arylene−vinylene conjugated polymers, 13 and 14, have been successfully synthesized through the Horner−Wadsworth−Emmons olefination of luminophoric dialdehydes 7 and 9 and bisphosphonate 12 in very good yields. They were characterized through 1H NMR, 13C NMR, IR, and elemental analysis. The investigation of their photophysical and electrochemical properties has been carried out. Although almost identical absorption and emission spectra were obtained in dilute chloroform solution for all polymers 13, the full width at half-maximum (fwhm) value of the emission curves depends on the length of the attached side chains. The presence of anthracenylene units in 14 leads to a red shift of its absorption and emission spectra relative to 13. Strong self-reabsorption after excitation in solution was observed for this polymer. The solid-state photophysical properties of 13 and 14 (photoconductivity, absorption and emission spectra, fluorescence quantum yield, Stokes shift, and fwhm) greatly depend on the nature (linear or branched), length, and location of the grafted alkoxy side groups. Photoconductivity is easily detected in polymers having octadecyloxy chains (13aa, 13ab, 14). Long linear (octadecyl, i.e., 13aa) or short branched (2-ethylhexyl, i.e., 13cc) side chains at position R2 (phenylene−vinylene segment) are necessary to obtain sharp and well-resolved emission spectra accompanied by high fluorescence quantum yields. The quasi-donor (phenylene−vinylene segment)−acceptor (arylene−ethynylene segment) nature of these polymers could explain the great discrepancy between the electrochemical band gap energy, Egec ≈ 1.60 eV, as obtained from the onset values of the redox potentials in cyclic voltammetry and in differential pulse polarography measurements, and the optical band gap energy, Egopt ≈ 2.30 eV, from the absorption spectra.

A Model Route Toward the Synthesis of Conformationally Constrained Polyhydroxylated Dipeptides from Natural Carbohydrates

Abstract: Enantiopure 6,7-diacetoxy-3- t -butoxycarbonylamino-azabicyclo[3.3.0]octan-2-one-8-carboxylic acid 14 (pyrrolizidi-none amino acid) was synthesized in 14 steps and 5.8% overallyield from tri- O -benzyl- D -arabinose 5 through the formyl C -imino-sugar 9 as a key intermediate. Key words: integrins, peptidomimetics, pyrrolizidinone aminoacids, reverse-turn, RGD The field of peptidomimetics 1 has gained an enormousimportance in recent years, particularly with the emer-gence of conformationally constrained systems that mim-ic certain structural features and therapeutic effects ofnatural peptides. 2 A special class of rigidified peptidomi-metics is constituted of the azabicyclo[X.Y.0]alkanoneamino acids 2b,3 1 (Figure 1), i. e. fused bicyclic dipeptidesthat simulate the bioactive conformation of the b-turnsites. 4 The stereocontrol 3,5 at the chiral carbon backboneand ring-fusion center, the side chain attachment, 6,7b andthe ring size, 5,8 are issues, which have been widely ad-dressed. These molecules have been used not only tomimic a dipeptide motif

Solubility and Solution Structure of Cellulose Derivatives

Strongly interacting solvents are needed to dissolve cellulose; therefore, in the past the interpretation of the uncommon solution behavior of cellulose and its derivatives was based mainly on energetic (enthalpic) considerations, for example, hydrogen bonding. These attempts have not been very successful. The present paper demonstrates that entropic effects influence the solution behavior much stronger than hitherto supposed. In the well-known Flory–Huggins theory the driving force for dissolution of flexible chains is the configurational entropy of mixing. This large entropy is strongly reduced by the chain stiffness of the cellulose backbone and by the strictly regular primary structure of this polysaccharide. It strongly reduces the driving force for dissolution. The entropy of mixing becomes largely increased again by the attachment of long side chains and causes solubility with surprising efficiency (hairy rod principle). This effect is demonstrated with several examples. Among others, the surprising insolubility of short, regular-selectively substituted cellulose chains is explained, although long chains of the same substitution pattern are soluble. The striking behavior of cellulose ethers in water is based on the hydrophobic effect, which causes an increased order of the polymer surrounding water molecules. The induced order results in a very pronounced decrease of entropy of mixing that overcompensates the positive configurational entropy of mixing. Common rules of basic thermodynamics now predict phase separation on heating, contrary to the Flory–Huggins theory, which can only predict phase separation on cooling.

Synthesis, characterisation and optical spectroscopy of diynes and poly-ynes containing derivatised fluorenes in the backbone

A series of trimethylsilyl-protected and terminal mono- and bis-alkynes based on 9,9-dioctylfluorene, 2-(trimethylsilylethynyl)-9,9-dioctylfluorene 1a, 2-ethynyl-9,9-dioctylfluorene 1b, 2,7-bis(trimethylsilylethynyl)-9,9-dioctylfluorene 2a, 2,7-bis(ethynyl)-9,9-dioctylfluorene 2b, have been synthesised. Reaction of trans-[(PnBu3)2PtCl2] with 2 equivalents of the terminal ethyne 1b yields the mononuclear platinum(II) diyne 3, reaction of trans-[(Ph)(Et3P)2PtCl] with 0.5 equivalents of the diterminal ethyne 2b gives the dinuclear platinum(II) diyne 4 while 1 ∶ 1 reaction between trans-[(PnBu3)2PtCl2] and 2b gives the platinum(II) poly-yne 5. Treatment of 2,5-dioctyloxy-1,4-diiodobenzene with 1b in 1 ∶ 2 stoichiometry produces the organic di-yne 6 while 1 ∶ 1 reaction between 2,5-dioctyloxy-1,4-diiodobenzene and 2b, 2,7-bis(ethynyl)fluorene or 2,7-bis(ethynyl)fluoren-9-one produces the organic co-poly-ynes 7–9. All the new materials have been characterised by analytical and spectroscopic methods and the single crystal X-ray structures of 2a and 3 have been determined. The diynes and poly-ynes are soluble in organic solvents and are readily cast into thin films. Optical spectroscopic measurements reveal that the attachment of octyl side-chains on the fluorenyl spacer reduces inter-chain interaction in the poly-ynes while a fluorenonyl spacer creates a donor–acceptor interaction along the rigid backbone of the organometallic poly-ynes and organic co-poly-ynes.

Highly Functionalized Pyrans Designed for Multipoint Side Chain Attachment to the F-Ring Sector of Spongistatin 1 (Altohyrtin A)

The synthesis of three potential F-ring components, variably functionalized for attachment to the chlorodiene side chain by differing chemical means, has been accomplished from D-(+)-mannose as the generic precursor.

Exciton migration to chain aggregates in conjugated polymers: influence of side-chain substitution

We have performed time-resolved photoluminescence (PL) measurements to study the transfer of excitons from non-interacting polymer chains to chain aggregates for thin films of polyindenofluorene with different attached side chains. The transfer time is shown to be fast (≈35 ps) and side-chain independent indicating that the substitution of different side chains does not affect the local concentration of aggregate sites within aggregate-containing domains, but rather the extent to which such domains are formed. We find the aggregate emission efficiency to be relatively high (≳20%) while still lower than the efficiency of emission from non-interacting chains.