A DFT Study on the One‐Electron Reduction/Oxidation of Biologically Relevant Pteridine Derivatives

Abstract

Pteridine derivatives occur ubiquitously in living systems. The biological functions of these nitrogen‐rich heterocyclic compounds remain partly unknown. The most intensively studied role is that of tetrahydrobiopterin as cofactor for the monooxygenases hydroxylating the aromatic amino acids phenylalanine, tyrosine and tryptophan. In these and other reactions pteridine derivatives act as redox catalysts; therefore, their redox behavior is of particular interest. Using density functional theory, one‐electron reduction/oxidation processes involving relevant pteridine derivatives in aqueous solution are studied. For pterins and lumazines, the results reproduce very satisfactorily the experimentally known increasing reductive strength in the order aromatic, dihydro and tetrahydro compound. The influence of simple substituents at different molecular sites is studied. Results on quinoid dihydropterins not only confirm earlier experimental conclusions regarding the structure of these quite instable compounds, they also provide a theoretical rationale why quinoid dihydrobiopterin may have evolved as intermediate in the cofactor role of tetrahydrobiopterin.

Theoretical determination of two-photon absorption in biologically relevant pterin derivatives

“…54,55 Optimisations utilised the B3LYP functional [56][57][58][59][60] with Grimme's D3 dispersion 61 and Becke-Johnson dampening [62][63][64][65] along with the 6-311G** basis set 66 with the determination of structural minima conducted through frequency analysis and noted by the presence of only positive curvature; the use of this model chemistry has been well established for giving appropriate geometry determinations for molecules of this type. 17,[67][68][69][70][71] TD-DFT data was determined using a series of DFT functionals, namely: CAM-B3LYP, 72 B3LYP, [56][57][58][59][60]74 and PBE0, 75 each with the Dunning cc-pVTZ basis. 76 CAM-B3LYP values are reported here due to their agreement with the UV-Vis spectra of folic acid, 77 as well as its robust performance on similar organic molecules.…”

“…9 Biopterin (BPT) has been found taking the role of a coenzyme in hydroxylation reactions in the metabolism of both amino acids and nitric oxide 10,11 while neopterin (NPT), a BPT metabolite, is synthesised predominantly in activated macrophages with high levels of NPT found in response to infections caused by viruses, parasites and intracellular bacteria. [12][13][14][15][16][17] Despite the role of 5,10-methenyltetrahydrofolylpolyglutamate, a derivative of folic acid (FA), in DNA repair as a light-harvesting antenna in DNA photolyases, [18][19][20] oxidised pterins have also been shown to cause photo-activated DNA damage when exposed to UV light. [21][22][23][24][25] The ability of pterins to produce singlet oxygen (O 2 ( 1 Δ g ), denoted as 1 O 2 for simplicity) 26,27 has garnered particular interest due to its role in photodynamic therapy (PDT).…”

Determination of two-photon absorption in nucleobase analogues: a QR-DFT perspective

“…Optimisations utilised the B97X-D functional [71], which has been shown to provide strong results for -stacking interactions [72][73][74][75], along with the cc-pVTZ basis set [76][77][78]; determination of structural minima was conducted through frequency analysis and noted by the presence of only positive curvature; the use of this model chemistry has been well established for giving appropriate geometry determinations for molecules of this type [79][80][81][82][83][84]. Geometry selection for hydrogen-bonded dimers was determined so as to mimic the hydrogen-bonded structures of correctly orientated Watson-Crick dimeric pairs.…”

Insights into Molecular Structure of Pterins Suitable for Biomedical Applications

“…Calculations for various pteridine compounds, both oxidized and reduced, revealed lumazine as the molecule with the highest oxidation potential (56.4 kcal mol −1 ) [ 134 ]. The reason, obviously, being the presence of two carbonyls in the pyrimidine ring.…”