calc_ionization: Calculate the ionization.

Description

This function calculates the ionization of a compound at a given pH. The pKa's are either entered as parameters or taken from a specific compound in the package. The arguments pKa_Donor and pKa_Accept may be single numbers, characters, or vectors. We support characters because there are many instances with multiple predicted values and all those values can be included by concatenating with commas (for example, pKa_Donor = "8.1,8.6". Finally, pka_Donor and pKa_Accept may be vectors of characters representing different chemicals or instances of chemical parameters to allow for uncertainty analysis. A null value for pKa_Donor or pKa_Accept is interpretted as no argument provided, while NA is taken as no equlibria

Usage

calc_ionization(
  chem.cas = NULL,
  chem.name = NULL,
  dtxsid = NULL,
  parameters = NULL,
  pH = NULL,
  pKa_Donor = NULL,
  pKa_Accept = NULL
)

Value

fraction_neutral: fraction of compound neutral
fraction_charged: fraction of compound charged
fraction_negative: fraction of compound negative
fraction_positive: fraction of compound positive
fraction_zwitter: fraction of compound zwitterionic

Arguments

chem.cas: Either the chemical name or the CAS number must be specified.
chem.name: Either the chemical name or the CAS number must be specified.
dtxsid: EPA's 'DSSTox Structure ID (https://comptox.epa.gov/dashboard) the chemical must be identified by either CAS, name, or DTXSIDs
parameters: Chemical parameters from a parameterize_MODEL function, overrides chem.name and chem.cas.
pH: pH where ionization is evaluated.
pKa_Donor: Compound H dissociation equilibirum constant(s). Overwrites chem.name and chem.cas.
pKa_Accept: Compound H association equilibirum constant(s). Overwrites chem.name and chem.cas.

Author

Robert Pearce and John Wambaugh

Details

The fractions are calculated by determining the coefficients for each species and dividing the particular species by the sum of all three. The positive, negative and zwitterionic/neutral coefficients are given by: $$zwitter/netural = 1$$ $$for(i in 1:pkabove) negative = negative + 10^(i * pH - pKa1 - ... - pKai)$$ $$for(i in 1:pkbelow) positive = positive + 10^(pKa1 + ... + pKai - i * pH)$$ where i begins at 1 and ends at the number of points above(for negative) or below(for positive) the neutral/zwitterionic range. The neutral/zwitterionic range is either the pH range between 2 pKa's where the number of acceptors above is equal to the number of donors below, everything above the pKa acceptors if there are no donors, or everything below the pKa donors if there are no acceptors. Each of the terms in the sums represent a different ionization.

References

Pearce, Robert G., et al. "Evaluation and calibration of high-throughput predictions of chemical distribution to tissues." Journal of Pharmacokinetics and Pharmacodynamics 44.6 (2017): 549-565.

Strope, Cory L., et al. "High-throughput in-silico prediction of ionization equilibria for pharmacokinetic modeling." Science of The Total Environment 615 (2018): 150-160.

Examples

Run this code

# Donor pKa's 9.78,10.39 -- Should be almost all neutral at plasma pH:
out <- calc_ionization(chem.name='bisphenola',pH=7.4)
print(out)
out[["fraction_neutral"]]==max(unlist(out))

# Donor pKa's 9.78,10.39 -- Should be almost all negative (anion) at higher pH:
out <- calc_ionization(chem.name='bisphenola',pH=11)
print(out)
out[["fraction_negative"]]==max(unlist(out))

# Fictitious compound, should be almost all all negative (anion):
out <- calc_ionization(pKa_Donor=8,pKa_Accept="1,4",pH=9)
print(out)
out[["fraction_negative"]]>0.9

# Donor pKa 6.54 -- Should be mostly negative (anion):
out <- calc_ionization(chem.name='Acephate',pH=7)
print(out)
out[["fraction_negative"]]==max(unlist(out))

#Acceptor pKa's "9.04,6.04"  -- Should be almost all positive (cation) at plasma pH:
out <- calc_ionization(chem.cas="145742-28-5",pH=7.4)
print(out)
out[["fraction_positive"]]==max(unlist(out))

#Fictious Zwitteron:
out <- calc_ionization(pKa_Donor=6,pKa_Accept="8",pH=7.4)
print(out)
out[["fraction_zwitter"]]==max(unlist(out))

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