This document discusses several key concepts in medicinal chemistry and pharmacology. It defines drug solubility, partition coefficients, dissociation constants, and plasma protein binding. It also explains ionization, bioisosterism, chelation, and hydrogen bonding - important molecular interactions that impact drug properties. Solubility, partitioning, dissociation, and protein binding influence how drugs are absorbed and distributed in the body. Ionization, bioisosterism, chelation, and hydrogen bonding can be exploited to optimize these parameters.

1. AIPS
IMRAN KHAN

2.  Drug solubility is defined as the maximum
concentration of a substance that can be
completely dissolved in a given solvent at a
certain temperature and pressure level.
Solubility of drugs is measured by the
amount of solvent needed to dissolve one
gram of the drug at a specific temperature

3.  Solubility is the property of a solid, liquid, or
gaseous chemical substance called solute to
dissolve in a solid, liquid, or gaseous solvent
to form a homogeneous solution of the solute
in the solvent. The solubility of a substance
fundamentally depends on the solvent used
as well as on temperature and pressure. The
extent of solubility of a substance in a
specific solvent is measured as the saturation
concentration where adding more solute does
not increase its concentration in the solution

4.  1.Structural modification
 2.Use of co-solvent
 3.employing surfactant
 4.Complexation

5.  Physical Modifications —
 Particle size reduction like micronization and
nanosuspension, modification of the crystal habit like
polymorphs, amorphous form and co crystallization,
drug dispersion in carriers like eutectic mixtures,
solid dispersions, solid solutions and cryogenic
techniques.
 Chemical Modifications —
 Change of ph, use of buffer, derivatization,
complexation, and salt formation.
 Miscellaneous Methods —
 Supercritical fluid process, use of adjuvant like
surfactant, solubilizers, co solvency, hydrotrophy,
and novel excipients.

6.  A partition coefficient is the ratio of the concentration
of a substance in one medium or phase (C1) to the
concentration in a second phase (C2) when the two
concentrations are at equilibrium; that is, partition
coefficient = (C1/C2)equil. The units of C1 and C2 may
be different. Commonly used partition coefficients in
inhalation toxic kinetics are the blood: air partition
coefficient for gases and the tissue: blood partition
coefficient for all substances. The constant for
partitioning between a gas and a liquid at low
concentrations is also called a Henry’s law
constant, H = (C1/C2)equil. The Henry’s law constant
(H) refers specifically to vapor–liquid equilibria.
Henry’s law usually applies over the concentration
range of interest in toxicology

7.  Partition coefficients are the ratio of the
concentration of an organic compound in two
phases that are in equilibrium with each other.
For example, in a two-layer system of water
(bottom layer) and an organic solvent(top layer),
an organic compound will be in one or the other
of the layers. After stirring and allowing time for
the layers to settle, the organic compound could
well be in both phases, albeit to a different
extent (concentration, C) in each phase. The
partition coefficient (K) is
 K=Corganic/Cwater


11.  in medicinal chemistry, bioisosteres are
chemical substituent or groups with similar
physical or chemical properties which
produce broadly similar biological properties
to another chemical compound.
Bioisoterism used to reduced toxicity ,change
bioavailability and activity of lead compound

13.  Classical bioisosterism was originally
formulated by James Moir and refined by
Irving Langmuir
 To the observation that different atoms with
same valance electrons structure and similar
biological properties
 For example replacement of H atom to F
Atom

17.  Chelation is a type of bonding of ions and
molecules to metal ions. It involves the formation
or presence of two or more separate coordinate
bonds between a polydentate (multiple bonded)
ligand and a single central metal atom.
 chelate, any of a class of coordination or
complex compounds consisting of a
central metal atom attached to a large molecule,
called a ligand, in a cyclic or ring structure. An
example of a chelate ring occurs in the
ethylenediamine-cadmium comple

19.  Essentially, the dissociation constant is the ratio of original
acid (reactants) to the dissociated ions (products). Ka is
the abbreviation for it. Our typical method for determining
the dissociation constant is to measure how much is
dissociated in water.
 In chemistry biochemistry and pharmacology,
a dissociation constant is a specific type of equilibrium
constant that measures the propensity of a larger object to
separate (dissociate) reversibly into smaller components,
as when a complex falls apart into its
component molecules, or when a salt splits up into its
component ions. The dissociation constant is
the inverse of the association constant. In the special case
of salts, the dissociation constant can also be called
an ionization constant. For a general reaction:

20.  The dissociation constant specifies the tendency of a
substance MxNy to reversibly dissociate (separate) in a
solution (often aqueous) into smaller components M and N
 where A represents the activity of a species, and [M], [N],
and [MxNy] are the molar concentrations of the entities M,
N, and MxNy. Because water is the solvent, and the solution
is assumed to be dilute, the water is assumed to be pure,
and the activity of pure water is defined as 1. The activities
of the solutes are approximated with molarities. The
dissociation constant is an immediate consequence of
the law of mass action which describes equilibria in a more
general way. The dissociation constant is also sometimes
called ionization constant when applied to salts. The
inverse of the dissociation constant is called association
constant

22.  A partition coefficient is the ratio of the concentration of a
substance in one medium or phase (C1) to the
concentration in a second phase (C2) when the two
concentrations are at equilibrium; that is, partition
coefficient = (C1/C2)equil.
 partition coefficient (P) or distribution coefficient (D) is the
ratio of concentrations of a compound in a mixture of
two immiscible solvents at equilibrium This ratio is
therefore a comparison of the solubility's of the solute in
these two liquids. The partition coefficient generally refers
to the concentration ratio of un-ionized species of
compound, whereas the distribution coefficient refers to
the concentration ratio of all species of the compound
(ionized plus un-ionized)

24.  A hydrogen bond (or H-bond) is a
primarily electrostatic force of attraction between
a hydrogen (H) atom which is covalently bound to
a more electronegative atom or group, and
another electronegative atom bearing a lone pair
of electrons—the hydrogen bond acceptor (Ac).
Such an interacting system is generally denoted
Dn–H···Ac, where the solid line denotes a
polar covalent bond, and the dotted or dashed
line indicates the hydrogen bond. The most
frequent donor and acceptor atoms are the
second-row elements nitrogen (N), oxygen (O),
and fluorine (F).

25.  Hydrogen bonds can be intermolecular (occurring between
separate molecules) or intramolecular (occurring among
parts of the same molecule).The energy of a hydrogen
bond depends on the geometry, the environment, and the
nature of the specific donor and acceptor atoms, and can
vary between 1 and 40 kcal/mol.This makes them
somewhat stronger than a van der Waals interactionand
weaker than fully covalent or ionic bonds. This type of
bond can occur in inorganic molecules such as water and
in organic moleculeslike DNA and proteins. Hydrogen
bonds are responsible for holding such materials
as paper and felted wool together, and for causing
separate sheets of paper to stick together after becoming
wet and subsequently drying.

27.  Plasma protein binding refers to the degree
to which medications attach to proteins
within the blood. A drug's efficiency may be
affected by the degree to which it binds. The
less bound a drug is, the more efficiently it
can traverse cell membranes or diffuse.

29.  ionization, in chemistry and physics, any
process by which electrically neutral atoms or
molecules are converted to electrically
charged atoms or molecules (ions). Ionization
is one of the principal ways that radiation,
such as charged particles and X rays,
transfers its energy to matter.

31.  AIPS
 IMRAN KHAN