Synthesis and stereochemistry of optically active biliverdin cyclic esters

Biliverdin chiral derivatives as chiroptical switches for pH and metal cation sensing

“…29,30 In the following we investigate molecules 1-6 by VCD, and perform DFT studies reproducing the VCD data with the aim of providing a solid ground to the picture of the helical conformation. This will allow us to confirm earlier conclusions 12 and to provide a quantitative estimate of the unbalance between P and M helicity imparted to the verdin skeleton by the chiral ester substituents, depending on the number of methylene units in the diester chain. In the second part of this work, we will study by ECD and by TD-DFT the dependence of spectroscopic response of some of the systems 1-6 on pH, as suggested by McDonagh for natural biliverdin by UV spectroscopy 1 and by Haidl et al through ECD.…”

“…The few chiroptical studies of biliverdin itself focused on optical activity induced by chiral complexing agents such as liposomes and micelles as well as proteins. 2,3,10 Some years ago, a few of us conceived of modulating the helicity of an optically active biliverdin, (bS,b 0 S)-dimethylmesobiliverdin-XIIIa 11,12 by linking its two propionic acid groups as diesters with diols of varying length to produce ''strapped'' biliverdins. 12 In the following, a Universita `di Brescia, Dipartimento di Medicina Molecolare e Traslazionale, Viale Europa 11, 25123 Brescia, Italy.…”

“…2,3,10 Some years ago, a few of us conceived of modulating the helicity of an optically active biliverdin, (bS,b 0 S)-dimethylmesobiliverdin-XIIIa 11,12 by linking its two propionic acid groups as diesters with diols of varying length to produce ''strapped'' biliverdins. 12 In the following, a Universita `di Brescia, Dipartimento di Medicina Molecolare e Traslazionale, Viale Europa 11, 25123 Brescia, Italy. E-mail: giovanna.longhi@unibs.it; Tel: +39-030-3717411 b Istituto Nazionale di Ottica (INO), C.N.R., Research Unit of Brescia, via Branze 45, 25123 Brescia, Italy c Regional Health Inspectorate, 7 Prince Al.…”

“…28 Herein we describe compounds 1-6 presented in Scheme 1, which had been previously synthesized and studied by NMR, ECD and Molecular Mechanics/Molecular Dynamics methods. 12 These cyclic diester analogs of biliverdin have their component dipyrrinones constrained to adopt a cisoid conformation and consequently to exhibit ECD spectra, which are quite sensitive to the number n of methylene units of the diester chain. Chiral biliverdin derivatives have been amply studied, not only for investigating aspects of the 3D structure of that medically important compound, but also to test its interaction with drugs, metals etcetera.…”

NMR Verification of Helical Conformations of Phycocyanobilin in Organic Solvents

“…In particular, spectroscopic studies have indicated that biliverdin dimethyl ester (BVE) is mostly in an (all-2,all-syn)-conformation in solution as well as in the crystal [6-1 I]. Application of COSY and two-dimensional spin-locked nuclear Overhauser effects (NOE) in 500-MHz 'H-NMR spectra of PCB in (D,)pyridine exhibited proton cross-peaks between the methine groups and the neighboring alkyl substituents on the pyrrole rings [12], which indicates that the (all-2,all-syn)-conformation predominates similarly to the case of BVE [8] [lo-131. Investigations using racemic mixtures of chiral BVs [7] [14], phycocyanobilin dimethyl ester (PCBE) [5] [15] and a chiral derivative [3], and optically active BVs [14] [16] also demonstrated that in solution helical species of type M and P2) are coexistent for all these compounds. Additional support has come forth from the fluorescence and fluorescence excitation spectra of PCBE in MeOH/Et,N 10: 1 which indicate that, in analogy to BVE, PCBE in solution is present in two families of conformers, one helical and the other one stretched [3].…”