Thionated organic compounds as emerging heavy-atom-free photodynamic therapy agents

Abstract

This minireview focuses on recent progress in developing heavy-atom-free photosensitizers based on the thionation of nucleic acid derivatives and other biocompatible organic compounds for prospective applications in photodynamic therapy.

Thionation of a Fluorescent Thieno[3,4-d]pyrimidine Derivative for the Development of a Heavy-Atom-Free Photosensitizer

“…Figure 1 shows the absorption spectra of ThiaHX and ThiathioHX in phosphate buffer solution (PBS) at pH 7.4 and in MeCN. As observed for the canonical nucleobases, [15][16]43 substitution of the oxygen atom of the carbonyl group by a sulfur atom at the C6 position results in a red shift of the lowest-energy absorption band from a maximum at 308 nm in ThiaHX in PBS to 367 nm in ThiathioHX (58 nm, 0.64 eV, or 5,145 cm -1 ). An absorption tail that extends to ca.…”

“…Importantly, thieno [3,4-d]pyrimidine-4(1H)-thione stands out as the most promising heavy-atom-free, pyrimidine-based photosensitizer developed to this date. Like the thiobases, 16 these compounds can be readily incorporated in specific DNA and RNA sequences for targeting tumors and are expected to function as Trojan horses 16 both in the absence and in presence of molecular oxygen, 13,15,42,44 facilitating more selective photodynamic therapy applications of skin cancer cells.…”

“…In this context, heavy-atom-free photosensitizers are emerging as an innovative class of photosensitizers exhibiting great potential for preclinical and clinical studies for the photodynamic treatment of cancers. Furthermore, heavy-atom-free photosensitizers (HAFPs) are receiving increased attention not only for PDT, [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] but also for photovoltaic, 28 and photocatalytic [29][30] applications, as well as for the development of innovative photonic technologies. [31][32][33] Some of the advantages of HAFPs over traditional photosensitizers include the high yield of triplet state population and the efficient generation of reactive oxygen species, low dark toxicity, long-lived excited triplet states, good photostability and biocompatibility, straightforward synthetic modification, and low cost.…”

Intramolecular Charge Transfer in the Azathioprine Prodrug Quenches Intersystem Crossing to the Reactive Triplet State in 6-Mercaptopurine

“…The low triplet yield is supported by the low 1 O2 yield reported in Table 7, and by the observation of phosphorescence at 77 K 62 for Aza but not at room temperature. The possibility that the triplet state of Aza can be populated is also indirectly supported by the observation of triplet state population in S 6 -methylthioinosine, which also features a C6-S single bond, in both aqueous and acetonitrile solutions. 63 Furthermore, transient absorption experiments performed for Aza in acetonitrile and in PBS at pH 7.4 in back-to-back conditions demonstrated nearly identical spectral features but a 44% slowdown of the charge recombination lifetime and a 2.6-fold increase in the amplitude of the longer-lived species in acetonitrile compared to pH 7.4 (Figure 5).…”

“…where 6 is the oxidation potential of 6MP determined using equation (1), 2 is the reduction potential of ground state O2, 6 is the adiabatic energy of the lowest-energy triplet state of 6MP, and C is the Coulombic interaction term experienced by the ion pair following the electron transfer process. 34 The latter term represents a small contribution to the overall energy change for neutral species in polar solvents 35 and has approximated to be 0.06 eV in acetonitrile.…”