Table of Contents
Physicochemical properties in relation to biological action
Physicochemical properties play an important role in determining the biological action of a substance. The way a substance interacts with its environment is determined by its physicochemical properties, such as solubility, surface area, and charge. These properties can affect the absorption, distribution, metabolism and excretion of a drug in the body. Understanding how physicochemical properties influence biological action is essential for developing new drugs and treatments.
These are various physicochemical properties as follows:
1. Ionization
2. Solubility
3. Partition coefficient
4. Hydrogen bonding
5. Protein binding
6. Chelation
7. Bioisosterism
8. Optical and geometric isomerism
1. Ionization
It is a process by which an atoms/molecules acquire a negative or positive charge by gaining or losing electrons. The resulting charged atom/molecules called an ion. Ionization is the process of converting atoms, molecules, or ions into electrically charged particles. It is an important physical process for the understanding of many chemical and biological processes. Through ionization, ions are formed which play an important role in atmospheric chemistry, nuclear fusion and matter-antimatter annihilation.
Relation to biological action
Role of ionization in biological action (activity) in humans (animals), it play an important role in pharmacokinetics (the movement of drugs in body). Pharmacokinetics involves ADME (absorption, distribution, metabolism and excretion). A good balance of “ionized-unionized” form is better for pharmacokinetics.
Pka value: – The cell membrane of stomach, small intestine, mucosa and nervous tissue are partially dipodic in nature. Most of the drug are either weakly acidic or weakly basic, the degree of dissociation (Pka) can be calculated using Henderson Hassel batch equation.
2. Solubility
The maximum amount of solute particles which can be dissolved in per 100ml/gm of solvent is called the “solubility of the drug” at given temperature. It depends on the “nature” of solute and solvent as well as “temperature“, “pH” & “pressure”. The atoms and molecules of all organic substance are held together by various types of “bonds”. Water constituent the major portion of living bodies. Therefore, the biochemical reactions & occurring within a living body rely either on the micro molecules dispersed in the phase.
Method to improve solubility of drugs
1. Alter the structure of molecules
2. Use of co-solvents
3. Addition of surfactants
4. Complexation
Relation to biological action
Bioavailability of drugs mainly depends on their solubility in the given solvent system. Drug (solute) must be in “solution” before it can be absorbed by biological membrane and show its activity. Drugs must be in solution to interact with receptor.
3. Partition coefficient
It is their ratio of concentration of a compound (drugs) in the two phases that equilibrium. The equilibrium consist of drug concentration in the two phase is termed as a partition coefficient. It is determined into vitro using n-octenol as the lipid phase and a pH 7.4 aqueous phosphate buffer as the water phase because it is a standardized measurement in living system in difficult partition of drug is expressed as:
Relation to biological action
1. It affect drug absorption and distribution.
2. It is generally used in combination with the Pka to predict the “distribution of drug” in biological system.
3. Since, biological membrane are lipophilic in nature show the rate of drug transfer is directly related to the “lipophilicity of the molecules“.
4. It is also help in to know the nature of drug that is hydrophilic or lipophilic for its solubility (bioavailability).
4. Hydrogen bonding
A bond in which hydrogen atoms hold to other atom together in termed as hydrogen bonds (H-bonds). The hydrogen bond is a specially dipole-dipole interaction between the hydrogen atom in a polar bond such as N-H, O-H or F-H and electronegative atom such as O, N, F atoms. When any highly electronegative atom (FON) is attached with hydrogen atom, then hydrogen atom become electron deficient and they make a weak attraction force bond with another electro rich molecule and this is called “hydrogen bonding” and it is represented by the dotted line.
Hydrogen bonding is classified into two types:
1. Intermolecular hydrogen bonding
When H-bonding is formed between two or more molecules. This gives association of molecules and forms dimers, and trimmers.
2. Intramolecular hydrogen bonding
When H-bonding is formed between two atoms within a molecule. This result in formation of Ring(chelation).
Relation to biological action
1. Maine physical properties are affected by hydrogen bonding.
2. It is very important in chemistry of genetic code.
3. Important in drug receptor interaction as well as their biological activity.
4. It will also increase the water solubility.
5. Protein binding
It is the process in which drug molecule bind with protein, it form a complex type of molecule and this phenomena is known as protein binding. After the absorption of drug when drug reaches into systematic circulation, it bind with the plasma protein which is already present in blood and form of “plasma protein drug complex“. These are some proteins which is present in blood: albumin, lipoprotein and globulins. When drug is combined with the protein they form two types of complex:
1. Reversible protein binding
In this, the drug is bind with a protein with very weak attraction forces like wonder wall forces and hydrogen bonding, so they can easily detach and drug become free and then this drug bind with receptor and give its pharmacological action.
2. Irreversible protein binding
The drug is bind with the protein with a strong bond like covalent bond, so they cannot detach then the drug don’t become free and it doesn’t bind with receptor due to it is not give any pharmacological action.
6. Chelation
This is a one form of complexation. A substance containing to or more legends (which has lone pair) (donor) group which is combine with a metal ion to form a complex known as chelates and the process is known chelation.
Relation to biological action
1. When metals like lead Mercury, iron and arsenic build up in our body they can be toxic.
2. In this EDTA is injected into the bloodstream then this bind with heavy metal and make a chelates and then remove heavy metal/minerals from the body.
7. Bioisosterism
The formal and 3D structure during SAR studies and drug design should be compared with other substituent and functional group of compare compound having similar biological activities. Bio isosteres is a medicinal chemistry approach for rotational designing of new drug applied with a lead compound using a process of molecular modification.
Relation to biological action
1. Bio isosteres are broadly used to pharmaceutical science.
2. It is used to reduce toxicity and change bio ability.
3. Help in production of drugs.
4. In drug design, the purpose of exchange one bio-isosteres for another is to enhance the desired biological or physical properties without change in their structure.
8. Optical isomerism
A drug therapeutic and toxic effect can be understand by the concept of stereo chemistry in enantiomers, symmetry, asymmetry and charity any drug is said to be chiral. If at least one is asymmetrical carbon atom and two enantiomers are present into the chemical and physical properties of each are the same but their interaction with receptors enzyme and proteins in the body is different as an individual.
Optical isomers are following type:
1. Enantiomers
A molecules and its mirror image when they are non-super impossible are known as Enantiomers. Chirality is the necessary and sufficient condition for the existence of enantiomers. A compound whose molecules are a chiral cannot exist as enantiomers. Ex- lactic acid, 2-methyl-1-butanol.
2. Di stereoisomers
When the optical isomers rotate the plane of a polarization light by different amounts these are called Di stereoisomers. Stereoisomers which are non-superimposable & also not the mirror image of each other are called as Di stereoisomers. Di stereoisomers contains the same functional group and hence show similar chemical properties but the chemical properties are not identical.
9. Geometrical isomerism
Geometrical isomerism is an important concept in organic chemistry. It refers to the phenomenon of molecules having the same atoms, but different spatial structures due to their double bonds. This type of molecule can be either cis or trans, and can cause a variety of physical and chemical properties in them. The position of the double bonds even affects how light interacts with molecules. This makes geometrical isomerism an incredibly useful tool for research, especially when it comes to designing new drugs or materials.