Current Organic Chemistry - Volume 15, Issue 6, 2011

In 1998, the development of cyclodextrin chemistry was reviewed comprehensively by a special issue in Chemical Review. Until now, thousands of papers about cyclodextrin chemistry have been published, including many new discoveries and achievements concerning organic chemistry. Here we present a special issue “Application of Cyclodextrins in Modern Chemistry—Based on Weak Molecule-molecule and Molecule-ion Interactions” to document the recent trends in the field of cyclodextrin chemistry. We would appreciate those scholars who wish to contribute a review article to the special issue. The contents of this special issue are listed as followed from many aspects. Kraus summarized his work in this field of cyclodextrins bearing pendant cationic or anionic moieties published till the year 2009, including most common synthetic methods for the preparation of charged cyclodextrin derivatives, and examples of their applications in bioorganic chemistry and pharmacy. Caira discussed structural aspects of crystalline cyclodextrin derivatives and their inclusion complexes. First, the role of single crystal XRD and the under-utilized power of powder XRD were evaluated, and a survey of crystal structures of pure CD hosts and CD inclusion compounds carried out during the last six years is presented. Then, the entries range from simple alkylated derivatives to elegant multisubstituted target CD molecules, with and without included guests. For the majority of the entries described, the main structural features gleaned by XRD methods are outlined and their relevance to applications is highlighted. Yamamoto et al. described effects of cyclodextrins on the conformation of proteins. The effects can be classified to those on the main chains as well as those on the side chains of amino acid residues of proteins. As another application using the effect of cyclodextrins on the main chain of protein, the technique of so called molecular imprinting is extensively studied. Cai et al. summarized a number of free-energy methods and how they were applied recently to the estimation of association free energies of CD inclusion complexes as a quantitative route towards an improved understanding of complexation processes. Dang et al. analyzed representative PXRD spectra of all kinds of CD complexes reported in these years. CD hydrates and CD inclusion complexes of organic compounds, polymers and transition metal coordination compounds were evaluated systematically. According to the results, the geometric differences in spatial structures of CD supramolecules were associated with the different intermolecular interactions due to different inclusion behaviors between CDs and guests. And several influence factors for the PXRD spectra of CD complexes were summarized. Pan et al. attempted to elucidate the role of CDs and their derivatives in regulation of the formation of inorganic nano particles (INPs) and formulates a simple relationship that will provide an insight into some of the strategies developed to improve the crystalline phase, surface area, particle size and morphology of INPs.

Cyclodextrins bearing pendant cationic or anionic moieties have been shown to form highly stable inclusion complexes with oppositely charged organic molecules. These charged hosts are also capable of molecular recognition of various organic cations and anions such as nucleotides and other phosphates, sulfates, sulfonates, carboxylates, enantiomers of amino acids, bile acids and many others. This review summarizes work in this field published till the year 2009 including most common synthetic methods for the preparation of charged cyclodextrin derivatives and examples of their applications in bioorganic chemistry and pharmacy.

Derivatization of cyclodextrins (CDs) demands creative chemistry and sound analytical characterization. Structural characterization of solid cyclodextrins and their inclusion compounds places strong reliance on X-ray diffraction (XRD) analysis. In this review, following introductory remarks on the role of single crystal XRD and the under-utilized power of powder XRD, a survey of crystal structures of pure CD hosts and CD inclusion compounds carried out during the last six years is presented. The entries range from simple alkylated derivatives to elegant multi-substituted target CD molecules, with and without included guests. For the majority of the entries described, the main structural features gleaned by XRD methods are outlined and their relevance to applications is highlighted.

The effects of cyclodextrins on the conformation of proteins can be classified to those on the main chains as well as those on the side chains of amino acid residues of proteins. Among those effects of cyclodextrins associated with the main chain, artificial chaperon function of large sized cyclodextrins, applied for the purpose of renaturating denatured synthesized proteins which were genetically produced using Bacillus coli as hosts, is widely utilized. As another application using the effect of cyclodextrins on the main chain of protein, the technique of so-called molecular imprinting is extensively studied. Those applications in these two fields will be shortly reviewed with regard to recent developments. Those effects of cyclodextrins associated with the side chains of proteins are interpreted as a result of inclusions of the side chains of aromatic amino acid residues. One typical effect of such inclusions, the lowering of the thermal stability of proteins will be introduced in this mini review.

In recent years, a variety of computational methods has been employed to investigate cyclodextrin (CD)-based systems. Among these methods, free-energy calculations occupy a prominent position, because they provide the key thermodynamic quantity that underlies the formation and the stability of CD complexes, together with the atomic-level detail often inaccessible to experiment. This review summarizes a number of free-energy methods and how the latter were applied recently to the estimation of association free energies of CD inclusion complexes as a quantitative route towards an improved understanding of complexation processes.

In the past three decades, powder X-ray diffraction (PXRD) analysis was widely used in the characterization of cyclodextrins (CDs) and their inclusion complexes. In this paper, representative PXRD spectra of all kinds of CD complexes reported in these years were reviewed. First of all, after comparing XRD spectra of CD hydrates, we found that some of water molecules crystallized in a crystal form played an important role in constructing a three-dimension structure. Next, differences and similarities in PXRD spectra of the inclusion complexes formed by CDs with organic compounds, polymers and transition metal coordination compounds were evaluated systematically. According to the results, the geometric differences in spatial structures of CD supramolecules were associated with the different intermolecular interactions due to different inclusion behaviors between CDs and guests. Finally, several influence factors for the PXRD spectra of CD complexes were summarized.

In recent years, nanomaterial science and supramolecular chemistry have experienced rapid development and attracted the interests of scientists from many diverse fields. Novel features have frequently served as paradigms for the study of the evolution of structural recombination between cation and anion ions by the means of molecule-ion interactions between inorganic ions and organic additives such as cyclodextrins (CDs). Actually, the presence of CDs as well as other additives has a significant influence on the size and morphology of inorganic nanoparticles (INPs) during the formation processes of INPs. However, why and how does the existence of CDs affect the growth of INPs? There was little information reported in available literatures. Accordingly, this current work attempts to elucidate the role of CDs and their derivatives in regulation of the formation of INPs and to compare with the effects of some surfactants, other amylases and polymers. Our motivation is to formulate a simple relationship that will provide an insight into some of the strategies developed to improve the crystalline phase, surface area, particle size and morphology of INPs.

The 2,3-dihydro-1,4-benzodioxin ring system is present in a large number of structures of therapeutic agents possessing important biological activities. Some of them are antihypertensive agents. Others are involved in nervous breakdown and schizophrenia or represent an attractive therapeutic target for the treatment of glaucoma. The 2,3-dihydro-1,4-benzodioxin core has also been developed for the synthesis of inhibitors of 5-lipoxygenase and accordingly, these 2,3-dihydro-1,4-benzodioxins are useful for the treatment of inflammatory diseases such as asthma and arthritis. The synthesis and reactivity of several bioisosteres of the non-aromatic ring will be discussed. The occurrence of the 2,3-dihydro-1,4-benzodioxin structure in various naturally abundant compounds is also known. The total synthesis of angustureine (a novel 1,2,3,4-tetrahydroquinoline alkaloid with a n-pentyl side chain at position 2) will be presented. The bioisosteric replacement of benzene by pyridine in compounds containing the 2-substituted-2,3-dihydro-1,4-benzodioxin core has yielded derivatives of biological interest in diverse therapeutic areas such as central nervous system and cardiovascular diseases. These promising results have prompted interest in the area of 1,4-dioxino-[2,3-b]pyridine analogues. Several modifications on both the aromatic and the non-aromatic rings will be reviewed, including several transformations of the new heterocycles, such as the Smiles rearrangement. Moreover, the enantiomers of 2- and 3-hydroxymethyl- 2,3-dihydro-1,4-dioxino-[2,3-b]pyridines, important chiral building blocks for the preparation of several biologically active compounds, have been synthesized. We have made an attempt to take into account the largest possible number of original papers, including our research and others. Publications of the last eleven years are included in this review.

Onopordum is an interesting genus belonging to the tribe Cardueae (Asteraceae family), and the species of this genus are used as food and in the popular medicine of several countries. The present paper reviews all the metabolites present in all the species of this genus, reported up to 2009, and several chemotaxonomic consideration have been made. Furthermore, the occurrence in other genus, the spectral data, the synthetic approaches, the chemical modifications and the biological properties of the sesquiterpenes of genus Onopordum have been reviewed.

Steroids comprise several classes of structurally related molecules with multiple bioactivities. Due to their complexity, the selective modification of these polycyclic compounds is challenging. This review outlines recent developments in the use of biocatalysts for the transformation of steroids, specifically focusing on the synthetic exploitation of hydrolases. Accordingly, several regio- and stereoselective acylations and deacylations mediated by lipases and proteases are discussed en route to preparation of new derivatives with useful application in pharmaceutical and food chemistry.

Quantum mechanical calculation clarified how the ylides exist in solution as a mixture of the two geometrical isomers (Z- and E-) as a major or minor form. In addition, Kinetic studies were made for the reaction between triphenylphosphine, di-tert-butyl acetylenedicarboxilate in the presence of protic/nucleophilic reagent, such as 2-aminothiophenol. To determine the kinetic parameters of the reaction, it was monitored by UV spectrophotometery. The values of the second order rate constant (k2) were calculated using standard equations within the program. At the temperature range studied the dependence of the second order rate constant (Ln k2) on reciprocal temperature was in a good agreement with Arrhenius equation. This provided the relevant plots to calculate the activation energy of the reaction. Furthermore, useful information was obtained from studies of the effect of solvent and concentration of reactants on the rate of reaction. Proposed mechanism was confirmed according to the obtained results and steady state approximation and first step (k2) of reaction was recognized as a rate determining step on the basis of experimental data.