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You can't just say "squeeze between hydrophobic polymers", as if that's a single thing, and therefore any such "hydrophobic polymer" will be vulnerable to a pht

by timr 2y ago

You can't just say "squeeze between hydrophobic polymers", as if that's a single thing, and therefore any such "hydrophobic polymer" will be vulnerable to a phthalate. In particular, DNA is not hydrophobic -- it's an extremely polar environment. The known DNA/RNA intercalating chemicals are also very polar (at least, in critical selected locations). For example, Ethidium Bromide: https://en.wikipedia.org/wiki/Ethidium_bromide https://en.wikipedia.org/wiki/Ethidium_bromide Point being: assuming that the paper in the headline is true (which I do not assume, but I digress), your theory of the mechanism is probably wrong, and therefore misleading. Edit: having now looked at the paper, they're discussing one specific chemical (bezyl butyl phthalate) which is actually quite polar. It's also an ester, and trivially broken down by common enzymes into a number of different child compounds, any of which could be individually responsible for the claimed effects. Biochemistry is complex.

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whatshisface 2y ago
It gets into hydrophobic binding sites, and accumulates in lipids. > Aromatic compounds, aliphatic hydrocarbons, and halogens are the hydrophobic parts of ligand PAEs. Hydrophobic contact is caused by the spatial proximity of the non-polar amino acid side chains and the hydrophobic substituents on the ligand PAE molecules. Water molecules are released from the hydrophobic region upon hydrophobic contact, and the unconstrained water molecules released can participate in the energy-favorable hydrogen bonding interactions, which enhance the overall binding affinity of the ligand [37,38,39]. Therefore, the hydrophobic interactions between ligands and receptors affect the ability of PAEs to bind to hormone proteins and influence the ability of PAEs to bind to DNA response elements. https://pmc.ncbi.nlm.nih.gov/articles/PMC10488033/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10488033/
- timr 2y ago
  The paper is about DNA mutation. DNA is not a hydrophobic binding site. It doesn't interact with hydrophobic binding sites. Moreover, the chemical studied in this particular paper is not particularly hydrophobic. Your theory is wrong, at least in this case. Also, this paper says the opposite of what you think it says: > based on the three-dimensional potential energy surface information, it was discovered that the hydrophobic, steric, and electrostatic fields of PAEs significantly influence their endocrine disruption effects on humans. They're saying that hydrophobic effects matter, but non-hydrophobic effects also matter. So everything matters. FWIW, the paper is not particularly worth citing. Someone made an ML model that said what any competent chemist could tell you by looking at a phthalate.
  - whatshisface 2y ago
    Who said DNA was hydrophobic? I'm sorry, but we're not disagreeing. Phtalates are very lithophilic and that's a major mechanism of their accumulation in the body. If phtalates were highly polar, they wouldn't be soluble in plastic. That means they're going to bind to fat tissue and non-polar receptors. >the chemical studied in this particular paper [...] Also, the paper didn't study "a chemical," it covered about 30.
    - timr 2y ago
      I'm telling you that you're overgeneralizing based on incorrect information. The paper being discussed here directly refutes your hypothesis of action, because it's about a particular chemical that is known to be metabolized, causing downstream effects in an extremely polar molecule (DNA). Generally, "pthalates" are not a thing, but rather a whole bunch of different things (some are hydrophobic, some are not), and many of them are metabolized by the human body, so they don't actually accumulate. You have to be more specific. https://pubmed.ncbi.nlm.nih.gov/17604388/ https://pubmed.ncbi.nlm.nih.gov/17604388/ > If phtalates were highly polar, they wouldn't be soluble in plastic. Setting aside "highly polar", which is not specific, you are wrong. Many/most pthalates are far from what chemists consider "hydrophobic", and are in fact esters, alcolhols and acids. > Also, the paper didn't study "a chemical," it covered about 30. The paper in the OP was about one molecule: BBP.
      - deleted 2y ago
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      - whatshisface 2y ago
        >Generally, "pthalates" are not a thing, but rather a whole bunch of different things (some are hydrophobic, some are not), and many of them are metabolized by the human body, so they don't actually accumulate. You have to be more specific. I am being specific enough to be talking about the hydrophobic pthalates that do accumulate in the human body. If I was talking about the other ones that claim would be trivially wrong... when the popular media says cyanide is dangerous, they're talking about the dangerous molecules with R-CN, not the safe ones.

by timr 2y ago

deleted 2y ago

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whatshisface 2y ago

It gets into hydrophobic binding sites, and accumulates in lipids. > Aromatic compounds, aliphatic hydrocarbons, and halogens are the hydrophobic parts of ligand PAEs. Hydrophobic contact is caused by the spatial proximity of the non-polar amino acid side chains and the hydrophobic substituents on the ligand PAE molecules. Water molecules are released from the hydrophobic region upon hydrophobic contact, and the unconstrained water molecules released can participate in the energy-favorable hydrogen bonding interactions, which enhance the overall binding affinity of the ligand [37,38,39]. Therefore, the hydrophobic interactions between ligands and receptors affect the ability of PAEs to bind to hormone proteins and influence the ability of PAEs to bind to DNA response elements. https://pmc.ncbi.nlm.nih.gov/articles/PMC10488033/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10488033/

timr 2y ago
The paper is about DNA mutation. DNA is not a hydrophobic binding site. It doesn't interact with hydrophobic binding sites. Moreover, the chemical studied in this particular paper is not particularly hydrophobic. Your theory is wrong, at least in this case. Also, this paper says the opposite of what you think it says: > based on the three-dimensional potential energy surface information, it was discovered that the hydrophobic, steric, and electrostatic fields of PAEs significantly influence their endocrine disruption effects on humans. They're saying that hydrophobic effects matter, but non-hydrophobic effects also matter. So everything matters. FWIW, the paper is not particularly worth citing. Someone made an ML model that said what any competent chemist could tell you by looking at a phthalate.
- whatshisface 2y ago
  Who said DNA was hydrophobic? I'm sorry, but we're not disagreeing. Phtalates are very lithophilic and that's a major mechanism of their accumulation in the body. If phtalates were highly polar, they wouldn't be soluble in plastic. That means they're going to bind to fat tissue and non-polar receptors. >the chemical studied in this particular paper [...] Also, the paper didn't study "a chemical," it covered about 30.
  - timr 2y ago
    I'm telling you that you're overgeneralizing based on incorrect information. The paper being discussed here directly refutes your hypothesis of action, because it's about a particular chemical that is known to be metabolized, causing downstream effects in an extremely polar molecule (DNA). Generally, "pthalates" are not a thing, but rather a whole bunch of different things (some are hydrophobic, some are not), and many of them are metabolized by the human body, so they don't actually accumulate. You have to be more specific. https://pubmed.ncbi.nlm.nih.gov/17604388/ https://pubmed.ncbi.nlm.nih.gov/17604388/ > If phtalates were highly polar, they wouldn't be soluble in plastic. Setting aside "highly polar", which is not specific, you are wrong. Many/most pthalates are far from what chemists consider "hydrophobic", and are in fact esters, alcolhols and acids. > Also, the paper didn't study "a chemical," it covered about 30. The paper in the OP was about one molecule: BBP.
    - deleted 2y ago
      [deleted]
    - whatshisface 2y ago
      >Generally, "pthalates" are not a thing, but rather a whole bunch of different things (some are hydrophobic, some are not), and many of them are metabolized by the human body, so they don't actually accumulate. You have to be more specific. I am being specific enough to be talking about the hydrophobic pthalates that do accumulate in the human body. If I was talking about the other ones that claim would be trivially wrong... when the popular media says cyanide is dangerous, they're talking about the dangerous molecules with R-CN, not the safe ones.