Said H. Hilal
Biographical Information
Name: Said H. Hilal
Title: Research Chemist
Education:
B.S. 1983 Chemistry Yarmouk University, Irbid, Jordan .
M.S. 1986 Chemistry Sam Houston State Univ., Huntsville, TX .
Ph.D. 1992 Physical Chemistry University of Georgia, Athens, Ga.
Expertise/Research Interests:
(A) Refinement and Extension of the SPARC Models to Describe the Behavior of Organic
Pollutants in the Environment
Mathematical models for predicting the transport and fate of pollutants in the environment require reactivity parameter values that is, the physical and chemical constants that govern reactivity. Although empirical structure activity relationships have been developed that allow estimation of some constants, such relationships are generally valid only within limited families of chemicals. A computer programs has been under development for more than 12 years that predicts a large number of chemical reactivity parameters and physical properties for a wide range of organic molecules strictly from molecular structure. This prototype computer program called SPARC (SPARC Performs Automated Reasoning in Chemistry) uses computational algorithms based on fundamental chemical structure theory to estimate a variety of reactivity parameters. This capability crosses chemical family boundaries to cover a broad range of organic compounds.
SPARC does not do "first principles" computation; rather, it analyzes chemical structure relative to a specific reactivity query much as an expert chemist might. SPARC utilizes directly the extensive knowledge base of organic chemistry. Organic chemists have established the types of structural groups or atomic arrays that impact certain types of reactivity and have described, in "mechanistic" terms, the effects on reactivity of other structural constituents appended to the site of reaction. To encode this knowledge base, a classification scheme was developed that defines the role of structural constituents in affecting or modifying reactivity. Furthermore, models have been developed that quantify the various "mechanistic" descriptions commonly utilized in structure activity analysis, such as induction, resonance and field effects. SPARC execution involves the classification of molecular structure and the selection and execution of appropriate "mechanistic" models to quantify reactivity.
A "toolbox" of mechanistic perturbation models has been developed that can be implemented where needed for a specific reactivity query. Resonance models were developed and validated on more than 5000 light absorption spectra whereas electrostatic interaction models were developed and validated on more than 4500 ionization pKas in water. Solvation models (i.e., dispersion, induction, H-bond and dipole interactions) have been developed and validated on more than 8000 physical property data points on properties such as vapor pressure, boiling point, solubility, Henry's constant, GC retention times and Kow. Ultimately, these mechanistic components will be fully implemented for the aforementioned chemical and physical process models, and they will be extended to additional properties such as hydrolytic and redox processes.
SPARC estimates numerous physical processes such as vapor pressure, boiling point, solubility, distribution coefficients, Henry's constant and GC/LC retention times for a large number of molecular structures. For chemical reactivity SPARC estimates pKa's in almost any solvent and in the gas phase, zwitterionic/hydration constants, tautomeric equilibrium, carboxylic acid ester hydrolysis rate constants, chemical reduction potential and electron affinity.
(B) Integrate SPARC with Metabolic Simulator for Computational Toxicology Research
Metabolites that form after an organism is exposed to a regulated chemical are often the cause of an observed toxic response in the target organism. Therefore, an accurate computerized simulator of metabolism is essential for meeting the objectives of the Computational Toxicology initiative. At the present time, many metabolic simulator programs are capable of mapping metabolic pathways for most chemical structures and stable metabolites are identified. However, due to several complicating factors, the generation of quantitatively accurate metabolites during simulation can sometime be problematic. Further development of these programs is required to produce a highly reliable simulator of metabolic activity for direct application to Computational Toxicology.
For example, a metabolic simulator of interest must allow for prioritization of many competing metabolic pathways for some chemicals. The prioritization process requires the integration of SPARC's physical/chemical properties calculator with the metabolic simulator of interest to provide a reliable estimation of many properties such as rate constant, solubility and partition coefficients of chemicals. Also, many of the metabolic simulator results can be confounded when the chemical species that is initially introduced in the environment undergoes some "change" prior to interacting with metabolizing enzymes. Perhaps the most important changes are chemical speciation (e.g., ionization, tautomerization, and hydration) and chemical hydrolysis. In effect, all the metabolic simulator algorithms may consider a chemical species or form that is functionally different from what is actually present. Efforts will focus on the extension of SPARC to characterize speciation phenomena into biological systems and the effects of speciation on the movement of chemicals through cellular membranes and their subsequent interaction with enzyme systems.
Professional Activities:
American Chemical Society
Select Publications:
S. H. Hilal, A. N. Saravanaraj, T. Whiteside, L. A. Carreira, "Calculating Physical Properties Of Organic Compounds For Environmental Modeling From Molecular Structure", J. Comput. Aided. Mol. Des. 21 69 2007.
Tad S. Whiteside, S.H. Hilal, and L.A. Carreira, "Estimation of Phosphate Ester Hydrolysis Rate Constants. II. Acid and General Base Catalyzed Hydrolysis ". QSAR Comb. Sci. 587 26 2007.
Tad S. Whiteside, S.H. Hilal, and L.A. Carreira, "Estimation of phosphate ester hydrolysis rate constants - alkaline hydrolysis." QSAR and Combinatorial Science, 123 25 2006.
S.H. Hilal, L.A. Carreira and L. L. Bornander, Hydration Equilibrium Constants of Aldehydes, Ketones and Quinazolines, QSAR and Combinatorial Science, 63 24 2005.
S.H. Hilal, L.A. Carreira and S.W. Karickhoff," Prediction of the Solubility, Activity Coefficient and Liquid/Liquid Partition Coefficient of Organic Compounds. ". QSAR and Combinatorial Science, 709 23 2004.
S.H. Hilal, L.A. Carreira and S.W. Karickhoff," Prediction of the Vapor Pressure, Boiling Point, Heat of Vaporization and Diffusion Coefficient of Organic Compounds ". QSAR and Combinatorial Science, 565 22 2003.
S.H. Hilal, L.A. Carreira, S.W. Karickhoff and B. P. Shrestha," Estimation of Carboxylic Acid Ester Hydrolysis Rate Constants". QSAR and Combinatorial Science, 917 22 2003.
S.H. Hilal, L.A. Carreira and S.W. Karickhoff," A Comprehensive Study of Molecular Speciation: Calculation of Microscopic and Zwitterionic Ionization Constants". Talanta ., 827 50 1999.
S.H. Hilal, L.A. Carreira and S.W. Karickhoff," Estimation of the Ionization pKa of Pharmaceutical Substances using SPARC". Talanta , 607 43 1996.
S.H. Hilal, L.A. Carreira and S.W. Karickhoff," A Rigorous Test for SPARC's Chemical Reactivity Models: Estimation of More Than 4300 Ionization pKas". Quant. Struct. Act. Relat., 348 14 1995.
Said Hilal, J.M Brewer, L. Lebioda and L.A. Carreira, " Calculated Effects of the Chemical Environment of 2-Phospho-D-Glycerate on the pKa of Its Carbon-2 and Correlation with the Proposed Mechanism of Action of Enolase". Biochem. Biophys. Res. Com., 607 211 1995.
S.H. Hilal, L.A. Carreira and S.W. Karickhoff, Quantitative Treatment of Solute/Solvent Interactions: Theoretical and Computational Chemistry, Ed., P. Polizer and J.S. Murray, Elsevier, Amsterdam, Vol. 1, 1994.
S.H. Hilal, L.A. Carreira, C. Melton, G. Baughman and S.W. Karickhoff, "Estimation of Ionization Constants of Azo Dyes and Related Aromatic Amines: Environmental Implication". J. Phys. Org. Chem., 122 7 1994.
S.H. Hilal, L.A. Carreira, C. M. Melton and S.W. Karickhoff, "Estimation of Gas Liquid Chromatographic Retention Times from Molecular Structure". J. Chromatogr. 662 269 1994.
S.H. Hilal,L.A. Carreira, C. M. Melton and S.W. Karickhoff," Estimation of Electron Affinity Based on Structure Activity Relationships". Quant. Struct. Act. Relat ., 389 12 1993.
S .H. Hilal, L.A. Carreira, C.M. Melton and S.W. Karickhoff, "Prediction of the Kovats Index of Non Polar Molecules on a Squalane Liquid Phase". Proceedings in Solute/Solvent Interactions, 257 1992.
Current Projects:
Refinement and validating of the SPARC chemical reactivity parameters and physical properties models.
Extension of the SPARC process models to estimate solution hydrolysis rate constants and one-electron reduction potential in any solvent of organic molecules.
Development of mathematical models to estimate heat of formation of organic molecule and prototype models to describe kinetics for abiotic reductive transformations in mineral suspensions.
Integration of SPARC physical property and chemical reactivity models with the metabolic simulator of interest to provide ionization pKa, speciation, tautomerization, hydration, hydrolysis, solubility and partition coefficients of organic compounds