Design and Synthesis of BODIPY-Hetero[5]helicenes as Heavy-Atom-Free Triplet Photosensitizers for Photodynamic Therapy of Cancer

Mrunesh Koli; Sonali Gupta; Saikat Chakraborty; Ayan Ghosh; Rajib Ghosh; A P Wadawale; Tapan K Ghanty; Birija S Patro; Soumyaditya Mula

doi:10.1002/chem.202301605

Design and Synthesis of BODIPY-Hetero[5]helicenes as Heavy-Atom-Free Triplet Photosensitizers for Photodynamic Therapy of Cancer

Chemistry. 2023 Oct 13;29(57):e202301605. doi: 10.1002/chem.202301605. Epub 2023 Jul 28.

Authors

Mrunesh Koli^{1

2}, Sonali Gupta^{1

2}, Saikat Chakraborty¹, Ayan Ghosh³, Rajib Ghosh^{2

4}, A P Wadawale⁵, Tapan K Ghanty^{2

6}, Birija S Patro^{1

2}, Soumyaditya Mula^{1

2}

Affiliations

¹ Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
² Homi Bhabha National Institute, Anushakti Nagar, Mumbai, 400094, India.
³ Laser and Plasma Technology Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
⁴ Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
⁵ Chemistry Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
⁶ Bio-Science Group, Bhabha Atomic Research Centre, Mumbai, 400085, India.

PMID: 37314387
DOI: 10.1002/chem.202301605

Abstract

Designing heavy-atom-free triplet photosensitizers (PSs) is a challenge for the efficient photodynamic therapy (PDT) of cancer. Helicenes are twisted polycyclic aromatic hydrocarbons (PAHs) with an efficient intersystem crossing (ISC) that is proportional to their twisting angle. But their difficult syntheses and weak absorption profile in the visible spectral region restrict their use as heavy-atom-free triplet PSs for PDT. On the other hand, boron-containing PAHs, BODIPYs are highly recognized for their outstanding optical properties. However, planar BODIPY dyes has low ISC and thus they are not very effective as PDT agents. We have designed and synthesized fused compounds containing both BODIPY and hetero[5]helicene structures to develop red-shifted chromophores with efficient ISC. One of the pyrrole units of the BODIPY core was also replaced by a thiazole unit to further enhance the triplet conversion. All the fused compounds have helical structure, and their twisting angles are also increased by substitutions at the boron centre. The helical structures of the BODIPY-hetero[5]helicenes were confirmed by X-ray crystallography and DFT structure optimization. The designed BODIPY-hetero[5]helicenes showed superior optical properties and high ISC with respect to [5]helicene. Interestingly their ISC efficiencies increase proportionally with their twisting angles. This is the first report on the relationship between the twisting angle and the ISC efficiency in twisted BODIPY-based compounds. Theoretical calculations showed that energy gap of the S1 and T1 states decreases in BODIPY-hetero[5]helicene as compared to planar BODIPY. This enhances the ISC rate in BODIPY-hetero[5]helicene, which is responsible for their high generation of singlet oxygen. Finally, their potential applications as PDT agents were investigated, and one BODIPY-hetero[5]helicene showed efficient cancer cell killing upon photo-exposure. This new design strategy will be very useful for the future development of heavy-atom-free PDT agents.

Keywords: BODIPY; helicenes; intersystem crossing; photodynamic therapy; triplet photosensitizers.

Grants and funding

Department of Atomic Energy, Govt. of India