Showing papers in "ChemInform in 2018"

The Photochemistry of Flavins

Abstract: The spectroscopic and photochemical properties of flavins have been extensively studied for over 40 years. Flavin photochemistry can be broadly divided into three categories: photoreduction, photoaddition, and photodealkylation. The involvement of the flavin triplet state in the primary step of intermolecular photoreductions was suggested by the observed inhibitory effect of excited state quenchers at concentrations far too low to affect the much shorter-lived excited singlet state. Several possible alternative reaction schemes involving dimeric triplet states, triplet-ground state reactions or triplet-triplet reactions may also contribute to the overall photoreduction reaction. Spectroscopic and thermochemical studies suggest that flavins may be weakly associated in most solvents. Intramolecular photoreduction involves dehydrogenation of the N(10)-hydroxyalkyl side chain to yield a variety of ketonic or aldehydic functions along with a corresponding reduction of the isoalloxazine nucleus. Photodealkylation involves loss of the N(10) side chain with the formation of alloxazines and an alkene.

Structure, Synthesis, and Physical Properties of Covalently Bound Flavins and 6- and 8-Hydroxyflavins

Abstract: The presence of flavins covalently bound to proteins in animal and plant tissues has been known since the mid-1950s when reports appeared that demonstrated a significant fraction of total tissue flavin became acid soluble only after proteolytic treatment of crude protein preparations. This chapter covers structures, molecular weights, and elemental composition of the riboflavin analogues. Of the flavin analogues covered in this chapter, the most detailed studies have been on the 8α-imidazolylflavins which are directly applicable to the 8α-histidylflavin analogues. The oxidation-reduction potential of the flavin analogues is a thermodynamic measure of the electron affinity of the substituted flavin ring. An unusual property of 8α-cysteinylsulfone flavins is that they undergo facile reductive cleavage to form cysteinesulfinic acid and riboflavin on reduction of the flavin by two electrons, whereas all other 8α-substituted flavins are stable to reduction. The synthesis of the flavin coenzyme involves 8-amino-8-demethylriboflavin as starting material.

Classical Methods of Preparation of Polymorphs and Alternative Solid Forms

Abstract: SOLID FORMS AND THEIR CHARACTERISTICS An awareness of the properties of the solid form in which drug substances (APIs) are manufactured and isolated today plays an important role in pharmaceuticals development. In the majority of cases a crystalline form is preferred, which enables the substance to be produced reliably and reproducibly with well-defi ned and characterized physical properties. However, a recent trend in pharmaceuticals development is a move toward APIs that are more lipophilic, hydrophobic, and insoluble in nature (1), and in these cases limitations in bioavailability may favor the development of amorphous or metastable forms with higher solubilities and dissolution rates (2). Whatever solid form is chosen will provide the starting point for the formulation of the drug, and the formulation and means of delivery will conversely exert requirements and restrictions on the solid form selection (3). For example, an amorphous API is not desirable for administration via a conventional dry powder inhaler.

Syntheses and Properties of 5-Deazaflavins

Abstract: This chapter focuses on the syntheses and properties of 5-deazaflavin derivatives from the viewpoints of synthetic organic chemistry. Polymers containing 5-deazaflavins as functional groups have been made through binding a polystyrene to the 3-position of 5-deazaflavins by a methylene linkage. Amphiphilic flavin (3-methyl-10-dodecylflavin) and 5-deazaflavin (3-methyl-10-dodecyl-5-deazaflavin) form micelle-like aggregates in aqueous solution to cause the decrease of their redox reactivities. However when the aggregates are dissolved in the micelle phase, the redox reactivities are enhanced. It was found that the reduction of carbonyl substrates by 1,5-dihydro-5-deazaflavin is automatically recycled in formic acid. α,β-Unsaturated carbonyl compounds can generally be reduced by hydride ion to give either α,β-unsaturated alcohols or α,β-saturated carbonyl compounds. The stereoselective nonenzymatic reduction of carbonyl groups by the dihydronicotinamide having chiral substituents, as NAD(P)H models, have been widely investigated, and the results have made an important contribution to asymmetrical synthesis.

Free Radicals as a Source of Uncommon Oxidation States of Transition Metals

Abstract: Free radicals and transition metal ions are ubiquitous in biological systems. The variable valency of transition metal ions plays a key role in the catalysis of redox processes in which the oxidation states of the metal are inherently unstable and/or have only a transient existence during the reaction sequence. A characteristic property of the transition metals in solution is that they are coordinated to ligands, so that one must consider the complete entity—metal center and ligands—in its reaction with free radicals. In aqueous media it is important to recognize that free radicals with a dissociable proton exist in acidic and basic forms that can have quite different reactivities. In order to study the kinetics and mechanisms of the reactions of free radicals, fast time-resolved methods are required because the rates of these processes often approach the diffusion-controlled limit.

Macrocyclic Complexes of Lanthanide Ions

Abstract: Trivalent lanthanides are naturally expected to be accommodated with various macrocyclic ligands to form stable complexes similarly to alkaline and alkaline earth metals because of the similarity of the ionic radii between lanthanides and Na+ or Ca2+ ions. Colors of most macrocyclic complexes with lanthanides are the same as those of the parent salts if the ligands are colorless. Vibrational spectra, especially Infrared (IR) spectra, have been measured for many lanthanide-macrocycle complexes. Solvent extraction of lanthanides with crown ethers has been investigated using picrate as a counteranion in most cases because of large distribution ratios. The divalent state of some lanthanide ions is stabilized by complexation with macrocyclic ligands, though divalent lanthanides are usually able to be oxidized to trivalent ones. Some lanthanide complexes with macrocycles are proposed as NMR shift reagents, as stated in the as Nuclear magnetic resonance (NMR) section. Luminescent lanthanide ions are often used as probes to solve analytical and structural problems.