Download Types of nucleic acids.

LECTERE 4
Heterocycles. Nucleic acids, classification, structure and
biological role.
Lecturer: Dmukhalska Ye. B.
PLAN
1. Heterocyclic compounds. Classification.
2. Five-ring heterocyclic compounds. Their properties and
structure. Properties of pyrole, imidazole, thiazole.
3. Six-ring and seven-ring heterocyclic compounds. Their
properties and structure. Properties of pyridine, diazines.
4. Bicyclic heterocyclic compounds, their biological role
(purine, and its derivative).
5. Alkaloids. Biological functions of alkaloids. Classes of
alkaloids.
6. Nucleic acids Types of nucleic acids. Nucleic acids
composition.
7. Levels of structural organization DNA. Biological functions.
Levels of structural organization RNA. Biological functions.
8. Use of synthetic nucleic acid bases in medicine.
• Heterocyclic compounds are cyclic compounds in
which one or more ring atoms are not carbon (that is,
hetero atoms).
• As hetero atom can be N, О, S, В, Al, Si, P, Sn, As, Cu.
Bat common is N, О, or S.
Classification
• Heterocycles are conveniently grouped into two
classes, nonaromatic:
and aromatic
• By size of ring
• Three-membered
four-membered
• five-membered
six-membered
Furan, Pyrrole, and Thiophene.
• These heterocycles have characteristics associated with
aromaticity. From an orbital point of view, pyrrole has
а planar pentagonal structure in which the four carbons
and the nitrogen have sp2 hybridization. Each ring atom
forms two sp2—sp2  bonds to its neighboring ring
atoms, and each forms one sp2 – s  bond to а
hydrogen. The remaining рz, orbitals on each ring atom
overlap to form а  molecular system in which the
three lowest molecular orbitals are bonding. The six 
electrons (one for each carbon and two for nitrogen) fill
the three bonding orbitals and give the molecule its
aromatic character. Furan and thiophene have similar
structures.
• The aromatic character of these heterocycles may also be
expressed using resonance structures, which show that а
pair of electrons from the hetero atom is delocalized
around the ring.
• The most general is the Paal-Кnоp synthesis, in which
а 1,4-dicarbonyl compound is heated with а
dehydrating agent, ammonia, or an inorganic sulfide to
produce the furan, pyrrole, or thiophene, respectively.
Reaction:
• The most typical reaction of furan, pyrrole,
and thiophene is electrophilic substitution.
• Pyrroles are polymerized by even dilute acids, probably by a
mechanism such as the following:
• Thiophen and furan are more stable and do not undergo
hydrolysis
• Reduction of pyrrole:
Condensed of thiophenes
• Pyrrole compounds occur widely in living systems. One of the
more important pyrrole compounds is the porphyrin hemin, the
prosthetic group of hemoglobin and myoglobin. А number of
simple alkylpyrroles have played an important role in the
elucidation of the porphyrin structures. Thus, drastic reduction of
hemin gives а complex mixture from which the four pyrroles,
hemopyrrole, cryptopyrrole, phyllopyrrole, and opsopyrrole, have
been isolated.
Tetrapyrrole compounds
• Azoles are five-membered ring aromatic
heterocycles containing two nitrogens, one
nitrogen and one oxygen, or one nitrogen
and one sulfur. They may be considered as
aza analogs of furan, pyrrole, and
thiophene, in the same way that pyridine is
an aza analog of benzene.
• Pyridine is an analog of benzene in which one of the СН units is
replaced by nitrogen. The nitrogen lone pair is located in an sp2
hybrid orbital which is perpendicular to the  system of the ring.
Various values have been deduced for the empirical resonance
energy of pyridine, but it would appear to be roughly
comparable to benzene. The resonance stabilization is shown by
the two equivalent Kekule structures and the three zwitterionic
forms with negative charge on nitrogen.
• Derivatives of pyridine are biological active compounds,
such as nicotine amide, nicotinic acid (vitamin PP).
nicotinic acid
• Diazines
• In this section, we shall take а brief look at another class of
heterocycles, the diazines. The three types of diazabenzenes are:
• In addition to these three diazines, the bicyclic tetraaza
compound, purine, is an important heterocyclic system.
• These ring systems, particularly that of pyrimidine, occur
commonly in natural products. The pyrimidines, cytosine,
thymine, and uracil are especially important because they are
components of nucleic acids, as are the purine derivatives adenine
and guanine.
• The рininе nucleus also occurs in such compounds as caffeine
(coffee and tea) and theobromine (cacao beans).
• Alkaloids constitute а class of basic, nitrogen
containing plant products that have complex
structures
and
possess
significant
pharmacological properties. The name
alkaloid, or "alkali-like," was first proposed by
the pharmacist W. Meissner in the early
nineteenth century before anything was known
about the chemical structures of the
compounds.
Nucleic acids
A most remarkable property of living cells is their ability to
produce exact replicas of themselves. Furthermore, cells contain
all the instructions needed for making the complete organism of
which they are а part. The molecules within а cell those are
responsible for these amazing capabilities are nucleic acids.
The Swiss physiologist Friedrich Miescher (1844 – 1895)
discovered nucleic acids in 1869 while studying the nuclei of
white blood cells. The fact that they were initially found in cell
nuclei and are acidic accounts for the name nucleic acid. Although
are now know that nucleic acids are found throughout а cell, not
just in the nucleus, the name is still used for such materials.
Types of nucleic acids.
Two types of nucleic acids are found within cells of
higher organisms: deoxyribonucleic acid (DNA) and
ribonucleic acid (RNA). Nearly all the DNA is found
within the cell nucleus. Its primary function is the
storage and transfer of genetic information. This
information is used (indirectly) to control many
functions of a living cell. In addition, DNA is passed
from existing cell to new cells during cell division
RNA occurs in all parts of a cell. It functions
primarily in synthesis of proteins, the molecules that
carry out essential cellular functions.
The monomers for nucleic acid polymers,
nucleotides, have а more complex structure than
polysaccharide monomers (monosaccharides) or
protein monomers (amino acids). Within each
nucleotide monomer are three subunits. А
nucleotide is, а molecule composed of a pentose
sugar bonded to both a group and a nitrogencontaining hetero-cyclic base.
• Pentose sugars.
• The sugar unit of а nucleotide is either the
pentose ribose or the 2-deoxyribose.
ribose
2-deoxyribose
Nitrogen-containing bases.
• Five nitrogen-containing bases are nucleotide
components. Three of them are derivatives of
pyrimidine, а monocyclic base with а sixmembered ring, and two are derivatives of purine,
а bicyclic base with fused five- and six-membered
rings.
Adenine
Guanine
Cytosine
Thymine
Uracil
Guaninosine
Adeninosine
Cytidine
Uridine
Thymidine
Nucleotide formation.
• The formation of а nucleotide from sugar, base, and phosphate
can be visualized as occurring in the following manner:
Nucleotide nomenclature.
Sugar
Nucleotide name
Nucleotide
abbreviation
Adenine
Deoxyribose
Deoxyadenosine-5’-monophosphate
dAMP
Guanine
Deoxyribose
Deoxyguanosine-5’-monophosphate
dGMP
Cytosine
Deoxyribose
Deoxycytidine-5’-monophosphate
dCMP
Thymine
Deoxyribose
Deoxythymidine – 5’-monophosphate
dTMP
Base
DNA Nncteothles
RNA Nncteothles
Adenine
Ribose
Adenosine-5’-monophosphate
AMP
Guanine
Ribose
Guanosine-5’-monophosphate
GMP
Cytosine
Ribose
Cytidine-5’- monophosphate
CMP
Uracil
Ribose
Uridine
UMP
Structure
• Primary nucleic acid structure is the sequence of nucleotides in
the molecule.
• The amounts of the bases А, Т, G, and С
present in DNA molecules were the key to
determination of the general threedimensional structure of DNA molecules.
Base composition data for DNA molecules
from many different organisms revealed а
definite pattern of base occurrence. The
amounts of А and Т were always equal, and
the amounts of С and G were always equal, as
were the amounts of total purines and total
pyrimidines.
• The relative amounts of these base pairs in
DNA vary depending on the life form from
which the DNA is obtained. (Each animal or
plant has а unique base composition.)
However, the relationships:
• %А =%Т and %C=%G
• always hold true. For example, human DNA
contains 30% adenine, 30% thymine, 20%
guanine, and 20% cytosine.
• А physical restriction, the size of the interior of the DNA
double helix, limits the base pairs that can hydrogen-bond
to one another. Only pairs involving one small base (а
pyrimidine) and one large base (а purine) correctly "fit"
within the helix interior. There is not enough room for two
large purine bases to fit opposite each other (they overlap),
and two small pyrimidine bases are too far apart to
hydrogen-bond to one another effectively. Of the four
possible purine – pyrimidine combinations (А – Т, А – С,
G – Т, and G – С), hydrogen-bonding possibilities are
most favorable for the А –Т and G – С pairings, and these
two combinations are the only two that normally occur in
DNA.
•
DNA molecules are the carriers of the genetic information
within а cell; that is, they the molecules of heredity. Each time а
cell divides, an exact copy of the DNA of the present cell is
needed for the new daughter cell. The process by which new
DNA molecule generated is DNA replication DNA replication is
the process by which DNA molecules produce exact duplicates
of themselves. The key concept in understanding DNA
replication is the base pairing associated with the DNA double
helix.
• We can divide the overall process of protein synthesis into two
steps. The first step is called transcription and the second
translation. Transcription is the process by which DNA directs
the synthesis of RNA molecules that carry the coded information
needed for protein synthesis. Translation is the process by which
the codes within RNA molecules are deciphered and а particular
protein molecule is formed. The following diagram summarizes
the relationship between transcription and translation.
Replication
transcription of DNA to form RNA
• Ribonucleic acids.
• Four major differences exist between RNA molecules and
DNA molecules.
• 1. The sugar unit in the backbone of RNA is ribose; it is
deoxyribose in DNA.
• 2. The base thymine found in DNA is replaced by uracil in
RNA (Figure.1). Uracil, instead of thymine, pairs with
(forms hydrogen bonds with) adenine in RNA.
• 3. RNA is а single-stranded molecule; DNA is doublestranded (double helix). Thus RNA, unlike DNA, does not
contain equal amounts of specific bases.
• 4. RNA molecules are much smaller than DNA molecules,
ranging from as few as 75 nucleotides to а few thousand
nucleotides.
Types of RNA molecules.
• Through transcription, DNA produces four types of RNA, distinguished
by their function. The four types are ribosomal RNA (rRNA), messenger
RNA (mRNA), primary transcript RNA (ptRNA), and transfer RNA
(tRNA).
• Ribosomal RNA combines with а series of protein to form complex
structures, called ribosomes that serve as the physical sites for protein
synthesis. Ribosomes have molecular masses on the order of 3 million.
The rRNA present in ribosomes has no informational function.
• Messenger RNA carries genetic information (instructions for protein
synthesis) from DNA to the ribosomes. The size (molecular mass) of
mRNA varies with the length of protein whose synthesis it will direct.
Each kind of protein in the body has its own mRNA.
• Primary transcript RNA in the material from which messenger RNA is
made.
• Transfer RNA delivers specific individual amino acids to the ribosomes,
the sites of protein synthesis. These RNAs are the smallest of the RNAs,
possessing only 75-99 nucleotide units.