To install StudyMoose App tap and then “Add to Home Screen”
Save to my list
Remove from my list
In this research work, we investigated the ionization processes of ampicillin in water at constant temperature (298.15 K) by ab initio and DFT methods. Using this investigation, for ampicillin in water, the value of the first ionization constant, pKa1, and the second ionization constant, pKa2 as well as structural properties such as dihedral angle between the indicated atoms (D), total atomic charge (Muliken) (q), bond lengths between the indicated atoms (d), and bond angle between the indicated atoms (A) were calculated at T = 298,15 K.
These structural properties were applied to indicate the strength of hydrogen bonding between ampicillin and water molecules.
In this research work, it was suggested that in aqueous solution, the anion and neutral species of ampicillin are solvated with four water molecules and also, the cation specie of ampicillin is solvated with three water molecules. In addition, it can be seen in this research work that for ampicillin in water, there is a comparable agreement between the experimentally determined and theoretically calculated pKa values at 298,18 K.
Antibiotics, also called antibacterial, are a type of antimicrobial drug that are used in the treatment and prevention of bacterial infections.
Verified writer
Proficient in: Physics
4.7 (346)
“ This writer never make an mistake for me always deliver long before due date. Am telling you man this writer is absolutely the best. ”
They may either kill or inhibit the growth of bacteria. It is possible to classify antibiotics by many different criteria like approval data, generation, chemical structure, antibacterial spectrum, pharmacokinetics, indications, tolerability, administration forms, and etc. Those antibiotics that target the bacterial cell wall like penicillin's have bactericidal activities. Ampicillin is a type of antibiotic that belongs to the penicillin group of beta-lactam antibiotics and is part of the amino penicillin family.
The chemical formula of ampicillin is C16H19N3O4S. It is roughly equivalent to amoxicillin in terms of activity.
Ampicillin and amoxicillin are in the list of the most consumed antibiotics. The discovery of ampicillin was a landmark in the era of antibiotics and it is still the most commonly prescribed class of antibiotics in human and veterinary medicine. Ampicillin is used in treatment of infections by many Gram-positive and Gram-negative bacteria. Ampicillin is comparatively less toxic than other antibiotics. In very rare cases, it causes side effects such as angioedema, anaphylaxis, and Clostridium difficile infection. Ampicillin can be administered by mouth, an intramuscular injection (shot) or by intravenous infusion.
Equilibrium constants for ionization reactions are usually called ionization constants or acidic dissociation constants (pKa). The pKa is an important physico-chemical parameter in drug absorption. Many drug compounds include at least one acid and/or basic group and the ionization state of these groups play an important role in determining the physico-chemical properties of a compound. Information of pKa value for compounds plays a major role in the expansion of drug formulations [12-14]. Various experimental procedures are frequently used to determine the acidity constants. These methods include high-pressure liquid chromatography (HPLC), liquid-liquid partitioning chromatography (LLPC), and methods that involve potentiometric titrations or spectrophotometric determination in water or in mixtures of solvents [15].
In the recent years, many research works were done for calculation of pKa values of different components. A part of these calculations were carried out using ab initio or DFT methods [16-23]. In DFT method, the calculation of electronic structure was performed with density functional theory and the electrostatic features were modeled through external charge distributions and continuum dielectrics. The paper deals with the influence of some factors such as the Self Consistent Reaction Field (SCRF) model applied, choice of a particular thermodynamic equation, atomic radii used to build a cavity in the solvent (water), optimization of geometry in water, inclusion of electron correlation, and the dimension of the basis set on the solvation free energies and on the calculated pKa values. In this paper, the pKa values of ampicillin were determined in aqueous solution by ab initio and DFT methods at T = 298.15 K. We considered various molecular conformations and solute-solvent interactions of the cation, anion, and neutral species of ampicillin using ab initio and density functional theory (DFT) methods to explain the calculated acidic dissociation constants.
In this research work, the PM3 method, in program Hyperchem version 7 for windows, was initially applied to optimize the structure of various species of ampicillin [24]. In next step, all initially optimal geometries were again optimized by Gaussian 98 program using the B3LYP/6-31 + G(d) levels of theory. These DFT and ab initio calculations were done using the hybrid exchange-correlation functional of Becke, Lee, Yang and Parr (B3LYP) and the Gaussian 6-31G (d) basis set [25]. The second optimization gave us the geometric data for all atoms of non-solvated and solvated species of ampicillin. Using these data, we could reach the value of Gibbs free energies (ΔG°).
The Polarized Continuum Model (PCM) of Tomasi et al. was used for analyzing the solvent effects on all species involved in the selected ionization reaction. In this method, the solvent is represented as a structure less polarizable medium characterized by its dielectric constant [26]. Finally, we selected the solvation of the species by means of intermolecular hydrogen bonds (IHBS) that involve one molecule of the mentioned species and some molecules of water.
An acidic molecule tends to lose its hydrogen atom when it is solved in water. This inclination is known as pKa [27]. Fully protonated ampicillin has two acidic groups: carboxyl and ammonium. A proton can be separated from either carboxyl or ammonium group to give different ionized species. Eqs. 1 and 2 can be applied for deprotonation process in carboxyl and ammonium groups, respectively. k1 and k2 show the microscopic ionization constants related to carboxyl and ammonium groups, respectively:
k1 = [H+][C15H16N2O2SCOO‒NH3+] / [C15H16N2O2SCOOHNH3+] (1)
And k2 can be related to deprotonation process about the ammonium group as Eq. 2:
k2 = [H+][C15H16N2O2SCOO‒NH2] / [C15H16N2O2SCOO‒NH3+] (2)
The computational study of ampicillin’s ionization processes in water at 298.15 K using ab initio and DFT methods reveals accurate pKa values and structural properties. The solvation characteristics indicate specific interactions between ampicillin species and water molecules, aiding in the understanding of its behavior in aqueous solutions. The comparable agreement between experimental and theoretical pKa values validates the effectiveness of computational methods in analyzing drug ionization processes, offering a reliable alternative to traditional experimental approaches.
Further research is encouraged to explore the ionization processes of other antibiotic compounds using similar computational methods, expanding our understanding of drug-solvent interactions and aiding in the development of more effective pharmaceutical formulations.
Ionization Processes of Ampicillin in Water: Ab Initio and DFT Study. (2024, Feb 23). Retrieved from https://studymoose.com/document/ionization-processes-of-ampicillin-in-water-ab-initio-and-dft-study
👋 Hi! I’m your smart assistant Amy!
Don’t know where to start? Type your requirements and I’ll connect you to an academic expert within 3 minutes.
get help with your assignment
