Adam Ibrahim | University College London (original) (raw)
Papers by Adam Ibrahim
International journal of pharmaceutics, 2007
Data on distribution coefficients from blood or plasma to rat skin and rabbit skin have been comp... more Data on distribution coefficients from blood or plasma to rat skin and rabbit skin have been compiled. From previous work on blood/plasma to brain or to muscle it is apparent that distributions from blood and plasma can be combined, and we show that it is possible to combine data on distribution to rat skin and rabbit skin. The combined set of blood/plasma distribution to rat and rabbit skin for 59 compounds, as logPskin, can be correlated through a linear free energy equation with a correlation coefficient of 0.856 and a standard deviation of 0.26 log units. The predictive capability of the equation has been assessed through training and test sets, and it is shown that the S.D. value of 0.26 log units is a good estimate of the predictive ability. The equation for logPskin has been compared to equations for a large number of possible model processes, using two mathematical methods. It is shown that there is no process amongst those we have examined that has any advantage over the pr...
Pest Management Science, 2013
Journal of Chromatography A, 2004
The use of gas-liquid chromatographic (GLC) retention data to obtain sets of solute descriptors i... more The use of gas-liquid chromatographic (GLC) retention data to obtain sets of solute descriptors is outlined, with reference to the schemes of Laffort and of Weckwerth. The method of Snyder and Dolan to obtain a set of solute descriptors from reverse phase high performance chromatographic (RP-HPLC) measurements is described. The work of Abraham on the construction of solvation parameters, or descriptors, from water-solvent partitions, GLC retention data and RP-HPLC data is considered in some detail. A comparison is made between the schemes of Laffort, Weckwerth and Abraham, and it is shown that the latter two yield exactly the same fits for a test data set of gas-methanol partition coefficients, although the distribution of chemical information amongst the terms in the multiple linear regressions is not quite the same. A comparison between the above 'experimental' descriptors and theoretical descriptors is made, and it is shown that the experimental Abraham and the theoretical Klamt descriptors encode almost the same chemical information. It is concluded that for processes that entail transfer of a solute from one phase to another, only a small number of solute descriptors, no more than five or six, is needed to provide a reasonably accurate analysis of the process.
Distribution coefficients, Kbi00d and KtiSSues (or biophase), from the gas phase to blood and gas... more Distribution coefficients, Kbi00d and KtiSSues (or biophase), from the gas phase to blood and gas phase to tissues (plasma, brain, fat, heart, liver, lung, kidney, muscle, urine, saline and olive oil) have been collected for large number of volatile organic compounds (VOCs). For these datasets of VOCs, linear free energy relationships (LFERs) have been established and Abraham equations have successfully been constructed to predict these distributions. It has also been shown that human and rat data for the air to blood and air to tissue distribution of VOCs can be combined. The differences in the two data sets, for the common compounds are smaller than the estimated inter-laboratory experimental error. The combination of the log KtiSSue values with values for air to blood yields distribution coefficients from blood to tissue, as log PtiSSue-Equations have successfully been constructed to predict these distributions. From a large amount of collected data on the distribution of drugs f...
Drug Discovery Today, 2002
Chemical Research in Toxicology, 2006
Distribution coefficients, K(mus), from the gas phase to the muscle have been collected for volat... more Distribution coefficients, K(mus), from the gas phase to the muscle have been collected for volatile organic compounds (VOCs). For 114 VOCs, a linear free energy relationship (LFER) yields an equation for log K(mus) with R(2) = 0.944 and SD = 0.267; construction of a training and test set shows that the LFER can predict further values to around 0.30 log units. The combination of the log K(mus) values with values for air to blood yields distribution coefficients from blood to muscle, log P(mus), for 110 VOCs; the corresponding LFER has R(2) = 0.537 and SD = 0.207 and a predictive capability of 0.22 log units. We also collected data on the distribution of drugs from blood or plasma to muscle and showed that the two sets of data can be combined. A LFER for blood/plasma to muscle for 59 drugs has R(2) = 0.745 and SD = 0.253 and a predictive capability of 0.25 log units. Finally, we show that the in vitro data on VOCs and the in vivo data on drugs can be combined; a LFER on the total data for 163 compounds has R(2) = 0.595, SD = 0.220, and a predictive capability of about 0.25 log units.
European Journal of Medicinal Chemistry, 2006
Partition coefficients, Kfat, from air to human fat and to rat fat have been collected for 129 vo... more Partition coefficients, Kfat, from air to human fat and to rat fat have been collected for 129 volatile organic compounds, VOCs. A linear free energy relationship, LFER, correlates the 129 values of logKfat with R2=0.958 and a standard deviation, S.D., of 0.194 log units. Use of training and test sets gives a predictive assessment of around 0.20 log units. Combination
Chemical Research in Toxicology, 2005
Journal of Chemical Information and Modeling, 2006
Fluid Phase Equilibria, 2007
Data have been assembled on gas to water partition coefficients for 374 compounds at 310K. It is ... more Data have been assembled on gas to water partition coefficients for 374 compounds at 310K. It is shown that an Abraham solvation equation with five descriptors can be used to correlate 350 such values, as logKW(310), with R2=0.994 and S.D.=0.154log units. Division into a training set and a test set shows that there is no bias in predictions and that
Chemosphere, 2015
A simple method is reported for the estimation of in vivo air-tissue partition coefficients of VO... more A simple method is reported for the estimation of in vivo air-tissue partition coefficients of VOCs and of in vitro blood-tissue partition coefficients for volatile organic compounds and other compounds. Linear free energy relationships for tissues such as brain, muscle, liver, lung, kidney, heart, skin and fat are available and once the Abraham descriptors are known for a compound, no more than simple arithmetic is required to estimate air-tissue and blood-tissue partitions.
Journal of Pharmaceutical Sciences, 2006
Journal of Chemical Information and Modeling, 2007
The ability to cross the blood brain barrier (BBB), sometimes expressed as BBB+ and BBB-, is a ve... more The ability to cross the blood brain barrier (BBB), sometimes expressed as BBB+ and BBB-, is a very important property in drug design. Several computational methods have been employed for the prediction of BBB-penetrating (BBB+) and nonpenetrating (BBB-) compounds with overall accuracies from 75 to 97%. However, most of these models use a large number of descriptors (67-199), and it is not easy to implement the models in order to predict values of BBB+/-. In this work, 19 simple molecular descriptors calculated from Algorithm Builder and fragmentation schemes were used for the analysis of 1593 BBB+/- data. The results show that hydrogen-bonding properties of compounds play a very important role in modeling BBB penetration. Several BBB models based on hydrogen-bonding properties, such as Abraham descriptors, polar surface area (PSA), and number of hydrogen bonding donors and acceptors, have been built using binomial-PLS analysis. The results show that the overall classification accuracy for a training set is over 90%, and overall prediction accuracy for a test set is over 95%.
European Journal of Medicinal Chemistry, 2008
European Journal of Medicinal Chemistry, 2006
European Journal of Medicinal Chemistry, 2007
Drug Discovery Today, 2002
Journal of Chromatography A, 2004
International journal of pharmaceutics, 2007
Data on distribution coefficients from blood or plasma to rat skin and rabbit skin have been comp... more Data on distribution coefficients from blood or plasma to rat skin and rabbit skin have been compiled. From previous work on blood/plasma to brain or to muscle it is apparent that distributions from blood and plasma can be combined, and we show that it is possible to combine data on distribution to rat skin and rabbit skin. The combined set of blood/plasma distribution to rat and rabbit skin for 59 compounds, as logPskin, can be correlated through a linear free energy equation with a correlation coefficient of 0.856 and a standard deviation of 0.26 log units. The predictive capability of the equation has been assessed through training and test sets, and it is shown that the S.D. value of 0.26 log units is a good estimate of the predictive ability. The equation for logPskin has been compared to equations for a large number of possible model processes, using two mathematical methods. It is shown that there is no process amongst those we have examined that has any advantage over the pr...
Pest Management Science, 2013
Journal of Chromatography A, 2004
The use of gas-liquid chromatographic (GLC) retention data to obtain sets of solute descriptors i... more The use of gas-liquid chromatographic (GLC) retention data to obtain sets of solute descriptors is outlined, with reference to the schemes of Laffort and of Weckwerth. The method of Snyder and Dolan to obtain a set of solute descriptors from reverse phase high performance chromatographic (RP-HPLC) measurements is described. The work of Abraham on the construction of solvation parameters, or descriptors, from water-solvent partitions, GLC retention data and RP-HPLC data is considered in some detail. A comparison is made between the schemes of Laffort, Weckwerth and Abraham, and it is shown that the latter two yield exactly the same fits for a test data set of gas-methanol partition coefficients, although the distribution of chemical information amongst the terms in the multiple linear regressions is not quite the same. A comparison between the above 'experimental' descriptors and theoretical descriptors is made, and it is shown that the experimental Abraham and the theoretical Klamt descriptors encode almost the same chemical information. It is concluded that for processes that entail transfer of a solute from one phase to another, only a small number of solute descriptors, no more than five or six, is needed to provide a reasonably accurate analysis of the process.
Distribution coefficients, Kbi00d and KtiSSues (or biophase), from the gas phase to blood and gas... more Distribution coefficients, Kbi00d and KtiSSues (or biophase), from the gas phase to blood and gas phase to tissues (plasma, brain, fat, heart, liver, lung, kidney, muscle, urine, saline and olive oil) have been collected for large number of volatile organic compounds (VOCs). For these datasets of VOCs, linear free energy relationships (LFERs) have been established and Abraham equations have successfully been constructed to predict these distributions. It has also been shown that human and rat data for the air to blood and air to tissue distribution of VOCs can be combined. The differences in the two data sets, for the common compounds are smaller than the estimated inter-laboratory experimental error. The combination of the log KtiSSue values with values for air to blood yields distribution coefficients from blood to tissue, as log PtiSSue-Equations have successfully been constructed to predict these distributions. From a large amount of collected data on the distribution of drugs f...
Drug Discovery Today, 2002
Chemical Research in Toxicology, 2006
Distribution coefficients, K(mus), from the gas phase to the muscle have been collected for volat... more Distribution coefficients, K(mus), from the gas phase to the muscle have been collected for volatile organic compounds (VOCs). For 114 VOCs, a linear free energy relationship (LFER) yields an equation for log K(mus) with R(2) = 0.944 and SD = 0.267; construction of a training and test set shows that the LFER can predict further values to around 0.30 log units. The combination of the log K(mus) values with values for air to blood yields distribution coefficients from blood to muscle, log P(mus), for 110 VOCs; the corresponding LFER has R(2) = 0.537 and SD = 0.207 and a predictive capability of 0.22 log units. We also collected data on the distribution of drugs from blood or plasma to muscle and showed that the two sets of data can be combined. A LFER for blood/plasma to muscle for 59 drugs has R(2) = 0.745 and SD = 0.253 and a predictive capability of 0.25 log units. Finally, we show that the in vitro data on VOCs and the in vivo data on drugs can be combined; a LFER on the total data for 163 compounds has R(2) = 0.595, SD = 0.220, and a predictive capability of about 0.25 log units.
European Journal of Medicinal Chemistry, 2006
Partition coefficients, Kfat, from air to human fat and to rat fat have been collected for 129 vo... more Partition coefficients, Kfat, from air to human fat and to rat fat have been collected for 129 volatile organic compounds, VOCs. A linear free energy relationship, LFER, correlates the 129 values of logKfat with R2=0.958 and a standard deviation, S.D., of 0.194 log units. Use of training and test sets gives a predictive assessment of around 0.20 log units. Combination
Chemical Research in Toxicology, 2005
Journal of Chemical Information and Modeling, 2006
Fluid Phase Equilibria, 2007
Data have been assembled on gas to water partition coefficients for 374 compounds at 310K. It is ... more Data have been assembled on gas to water partition coefficients for 374 compounds at 310K. It is shown that an Abraham solvation equation with five descriptors can be used to correlate 350 such values, as logKW(310), with R2=0.994 and S.D.=0.154log units. Division into a training set and a test set shows that there is no bias in predictions and that
Chemosphere, 2015
A simple method is reported for the estimation of in vivo air-tissue partition coefficients of VO... more A simple method is reported for the estimation of in vivo air-tissue partition coefficients of VOCs and of in vitro blood-tissue partition coefficients for volatile organic compounds and other compounds. Linear free energy relationships for tissues such as brain, muscle, liver, lung, kidney, heart, skin and fat are available and once the Abraham descriptors are known for a compound, no more than simple arithmetic is required to estimate air-tissue and blood-tissue partitions.
Journal of Pharmaceutical Sciences, 2006
Journal of Chemical Information and Modeling, 2007
The ability to cross the blood brain barrier (BBB), sometimes expressed as BBB+ and BBB-, is a ve... more The ability to cross the blood brain barrier (BBB), sometimes expressed as BBB+ and BBB-, is a very important property in drug design. Several computational methods have been employed for the prediction of BBB-penetrating (BBB+) and nonpenetrating (BBB-) compounds with overall accuracies from 75 to 97%. However, most of these models use a large number of descriptors (67-199), and it is not easy to implement the models in order to predict values of BBB+/-. In this work, 19 simple molecular descriptors calculated from Algorithm Builder and fragmentation schemes were used for the analysis of 1593 BBB+/- data. The results show that hydrogen-bonding properties of compounds play a very important role in modeling BBB penetration. Several BBB models based on hydrogen-bonding properties, such as Abraham descriptors, polar surface area (PSA), and number of hydrogen bonding donors and acceptors, have been built using binomial-PLS analysis. The results show that the overall classification accuracy for a training set is over 90%, and overall prediction accuracy for a test set is over 95%.
European Journal of Medicinal Chemistry, 2008
European Journal of Medicinal Chemistry, 2006
European Journal of Medicinal Chemistry, 2007
Drug Discovery Today, 2002
Journal of Chromatography A, 2004