Solubilization of <i>meso</i>-Tetraphenylporphyrin Photosensitizers by Substitution with Fluorine and with 2,3-Dihydroxy-1-propyloxy Groups
Bibliographic record
Abstract
The tetra(hydroxyphenyl)porphyrins (5,10,15,20-tetrakis(2-hydroxyphenyl)porphyrin (3), 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (4), and 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin (5) and the tetrahydroporphyrins (5,10,15,20-tetrakis(2-fluoro-3-hydroxyphenyl)porphyrin (6), 5,10,15,20-tetrakis(2,4-difluoro-3-hydroxyphenyl)porphyrin (7), and 5,10,15,20-tetrakis(3,5-difluoro-4-hydroxyphenyl)porphyrin (8)) have been reported as potential photosensitizers for photodynamic therapy. In particular, the tetrahydroporphyrin 7, which has been in Phase III clinical trials for three years in the USA and Canada, has shown great promise for primary and recurrent head and neck cancer. It is expected to be on the market soon. A potentially limiting property of compounds 3-8 is their hydrophobicity, which renders them insoluble in aqueous media. We therefore set out to develop an approach for their solubilization in aqueous media. The first attempt was to prepare analogues with fluorine substituents at the positions ortho to each of the four hydroxy groups on the meso-phenyl rings. This was expected to increase the acidity of the ortho hydroxy groups, and therefore the solubility of the compounds in hydroxylic media. This structural alteration resulted in a slight but significant decrease in the partition coefficients. The second attempt was substitution of each of the hydroxy groups on the phenyl rings with 2,3-dihydroxy-1-propyloxy groups. This structural alteration resulted in a substantial decrease in the partition coefficients. To harness the combined effect of these two structural variations porphyrins were prepared containing both 2,3-dihydroxy-1-propyloxy and ortho fluorine groups on the meso-phenyl rings. The partition coefficients decreased by more than two orders of magnitude. The most significant decrease was due to the substitution with 2,3-dihydroxy-1-propyloxy groups, rather than the substitution with fluorine, although fluorination alone contributed significantly. The effect of this method was demonstrated most clearly by comparison of the partition coefficients of meta and para isomers of these porphyrins.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".