New Conjugatable Platinum(II) Chlorins: Synthesis, Reactivity and Singlet Oxygen Generation
Abstract
1. Introduction
2. Results and Discussion
2.1. Synthesis
- (1)
- Replacing PtCl2 with a platinum salt less susceptible to oxidation (K2PtCl4). However, there was no better progression of the reaction, even increasing the reaction time to 2 h (entries 1–5, Table 1).
- (2)
- Verifying the release of HCl in the reaction mixture with PtCl2—we decided to use a base (Na2CO3) to reduce the temperature and increase the reaction time. However, a complete conversion of the porphyrin into the platinum(II) complex was not observed (entry 6, Table 1).
- (3)
- The use of a platinum salt soluble in organic solvents—bis(benzonitrile)platinum(II) dichloride—significantly improved the yield of complex PtP1. In this case, it was possible to replace benzonitrile with chlorobenzene as a solvent with a lower boiling point, facilitating the distillation step at the end of the reaction. Using these conditions in the presence of a base (NaOAc or Na2CO3), at a lower temperature (150 °C), it was possible to isolate platinum complex PtP1 (Scheme 1) in satisfactory yield (entries 7–8, Table 1).
Entry | Pt(II) Salt (Equiv.) | Solvent | Base (Equiv.) | P1 (mol/dm3) | Temp. (°C) | Time (min) | PtP1 (%) |
---|---|---|---|---|---|---|---|
1 | K2PtCl4 (3) | benzonitrile | - | 0.005 | 250 | 20 | Mixture with P1 |
2 | K2PtCl4 (3) | benzonitrile | - | 0.004 | 250 | 20 | Mixture with P1 |
3 | K2PtCl4 (3) | benzonitrile | - | 0.004 | (1) 180; (2) 200 | 20 + 20 | Mixture with P1 |
4 | K2PtCl4 (3) | benzonitrile | - | 0.006 | 230 | 20 | Mixture with P1 |
5 | K2PtCl4 (3) | benzonitrile | - | 0.005 | 250 | 120 | Mixture with P1 |
6 | PtCl2 (3) | benzonitrile | Na2CO3 (19) | 0.011 | 150 | 60 + 120 | Mixture with P1 |
7 | PtCl2(PhCN)2 (2) | chlorobenzene | NaOAc (5) | 0.041 | 150 | 60 + 60 | 83 |
8 | PtCl2(PhCN)2 (2) | chlorobenzene | Na2CO3 (5) | 0.041 | 150 | 60 + 60 | 93 |
2.2. Characterization of Compounds
3. Experimental Section
3.1. Materials and Methods
3.2. Synthesis of PtP1
3.3. 1,3-DC Reaction of PtP1 with Azomethine Ylide
3.4. Ester Hydrolysis
3.4.1. Synthesis of PtP2
3.4.2. Synthesis of PtC2
3.5. Conjugation with Indomethacin Derivative
3.5.1. Synthesis of PtP2-Ind
3.5.2. Synthesis of PtC2-Ind Conjugate
3.6. Singlet Oxygen Generation
3.7. DFT Calculations
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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λmax/nm (logε) | |||||
---|---|---|---|---|---|
Soret Band | Q Bands | ||||
P2 | 413 (5.44) | 507 (4.23) | 536 (3.46) | 581 (3.73) | 652 (3.35) |
PtP2 | 394 (5.31) | 507 (4.23) | 539 (4.18) | ||
C2 | 408 (5.14) | 503 (4.08) | 530 (3.79) | 594 (3.68) | 648 (4.64) |
PtC1 | 394 (5.25) | 476 (3.89) | 549 (4.03) | 591 (4.78) | |
PtC2 | 394 (5.16) | 476 (3.81) | 549 (3.97) | 591 (4.72) | |
PtC3 | 395 (5.27) | 481 (4.03) | 560 (4.19) | 598 (4.80) | |
PtP2-Ind | 393 (5.44) | 507 (4.29) | 539 (4.29) | ||
PtC2-Ind | 394 | 476 | 549 | 591 |
PtP2 triplet | +154.5 kJ/mol compared to the energy of the singlet. |
PtC2 triplet | +137.4 kJ/mol compared to the energy of the singlet. |
PtC4 triplet | +138.1 kJ/mol compared to the energy of the singlet. |
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Almeida, J.; Barone, G.; Cunha-Silva, L.; Cerqueira, A.F.R.; Tomé, A.C.; Rangel, M.; Silva, A.M.G. New Conjugatable Platinum(II) Chlorins: Synthesis, Reactivity and Singlet Oxygen Generation. Molecules 2025, 30, 2496. https://doi.org/10.3390/molecules30122496
Almeida J, Barone G, Cunha-Silva L, Cerqueira AFR, Tomé AC, Rangel M, Silva AMG. New Conjugatable Platinum(II) Chlorins: Synthesis, Reactivity and Singlet Oxygen Generation. Molecules. 2025; 30(12):2496. https://doi.org/10.3390/molecules30122496
Chicago/Turabian StyleAlmeida, José, Giampaolo Barone, Luís Cunha-Silva, Ana F. R. Cerqueira, Augusto C. Tomé, Maria Rangel, and Ana M. G. Silva. 2025. "New Conjugatable Platinum(II) Chlorins: Synthesis, Reactivity and Singlet Oxygen Generation" Molecules 30, no. 12: 2496. https://doi.org/10.3390/molecules30122496
APA StyleAlmeida, J., Barone, G., Cunha-Silva, L., Cerqueira, A. F. R., Tomé, A. C., Rangel, M., & Silva, A. M. G. (2025). New Conjugatable Platinum(II) Chlorins: Synthesis, Reactivity and Singlet Oxygen Generation. Molecules, 30(12), 2496. https://doi.org/10.3390/molecules30122496