Extraction and identification of anthocyanins

The use of organic solvents such as methanol and ethanol to extract anthocyanin pigments causes a toxicity issue.

 Although ethanol is considered as a generally safe extraction medium, isolation of anthocyanins using water-based extraction is consider a greener way.

  This extraction technique uses acidified water (0.01% HCl, pH ~2.3) that is subjected to high temperatures between 110–160°C under a constant pressure of 40 bars

  This increases the solubility of anthocyanins from the plant during extraction with water.

Anthocyanins are extracted from plants as a crude mixture. For that reason, separation or isolation of specific type of anthocyanin is needed for a specific purpose. 

 These include thin layer chromatography, high speed countercurrent chromatography, high-performance liquid chromatography, cellulose column chromatography, and reversed-phase ion-pair chromatography, as well as gas chromatography.

 In addition to separation and identification of anthocyanins, quantification of these compounds is commonly done by various chromatographic methods. High-performance liquid chromatography is the most used method in quantification of anthocyanins. 

Anthrocyanin and its types

Anthocyanins are blue, red, or purple pigments found in plants, especially flowers, fruits, and tubers. In acidic condition, anthocyanin appears as red pigment while blue pigment anthocyanin exists in alkaline conditions. Anthocyanin is considered as one of the flavonoids although it has a positive charge at the oxygen atom of the C-ring of basic flavonoid structure. It is also called the flavylium (2-phenylchromenylium) ion.

anthocyanidins and anthocyanins possess antioxidative and antimicrobial activities, improve visual and neurological health, and protect against various non-communicable diseases. These studies confer the health effects of anthocyanidins and anthocyanins, which are due to their potent antioxidant properties.

Different mechanisms and pathways are involved in the protective effects, including free-radical scavenging pathway, cyclooxygenase pathway, mitogen-activated protein kinase pathway, and inflammatory cytokines signaling. 

Anthocyanin is one of the subclasses of phenolic phytochemicals. Anthocyanin is in the form of glycoside while anthocyanidin is known as the aglycone.

Anthocyanidins are grouped into 3-hydroxyanthocyanidins, 3-deoxyanthocyanidins, and O-methylated anthocyanidins, while anthocyanins are in the forms of anthocyanidin glycosides and acylated anthocyanins. The most common types of anthocyanidins are cyanidin, delphinidin, pelargonidin, peonidin, petunidin, and malvidin. 

Anthocyanin is derived from flavonol, and it has the basic structure of flavylium ion, that is a lack of a ketone oxygen at the 4-position

Different mechanisms and pathways are involved in the protective effects, including free-radical scavenging pathway, cyclooxygenase pathway, mitogen-activated protein kinase pathway, and inflammatory cytokines signaling

Flavonoids

Flavonoids, as an important class of natural products, are the main bioactive constituents of a lot of medicinal or dietary plants. They have been reported to show extensive benefits to human health, including antioxidant, anti-inflammatory, and anti-cancer activities.
 In most cases, flavonoids are present in plants as a series of analogues with similar structures and physico-chemical properties.
 This chemical complexity renders the quality control of flavonoid-containing herbal products problematic. Therefore, rapid, accurate and sensitive analytical techniques for flavonoids are of significance.

Bacteriochlorin

Bacteriochlorins such as bacteriochlorophyll a absorb strongly in the near-infrared spectral region and are potentially useful in a variety of photochemical fields.

 De novo syntheses of bacteriochlorins entail self-condensation of a dihydrodipyrrin-acetal (containing one pyrrole and one pyrroline joined via a methylidene bridge) either via a heavily studied Eastern–Western (E–W) route or a recently reported Northern–Southern (N–S) route.

 The Michael addition to form the dihydrodipyrrin-acetal for the E–W approach has limited scope for the installation of substituents on the pyrroline units. By use of the N–S route, new bacteriochlorins have been prepared that bear a pair of aryl or alkyl groups, together termed a “swallowtail” substituent, at each β-pyrroline unit, a previously inaccessible design. 

Single-crystal X-ray structures of three intermediates were determined. Bacteriochlorins synthesized herein exhibit characteristic bacteriochlorophyll-like absorption spectra, including a Qy band in the region of 730–758 nm. 

The swallowtail groups have little impact on the excited-state properties of the bacteriochlorins, and the slight changes of spectral properties that are observed stem from substituent electronic effects rather than changes in structure.

 In summary, introduction of an integral swallowtail unit on the pyrroline ring opens new sites for tailoring molecular designs without altering the attractive photophysical features of the synthetic bacteriochlorins.

Chlorins are porphyrins with one beta-saturated pyrrolic ring destroying the p-conjugation at the beta-carbons. The saturation of the beta-carbons e†ectively prevents the ring current from taking the outer route at that particular pyrrolic unit. Since chlorins have 24p-electrons, all p-electrons cannot directly participate in the aromatic pathway. However, when one considers the aromatic pathway to be a superposition of several 22p-electron paths, all 24p-electrons can form the total aromatic pathway. For chlorins, pyrrolic rings with an inner hydrogen have strong local ring currents. For and t-CH2 (a) cCH the pyrrolic ring without an inner hydrogen has a 2 (b), NICS values which is twice as large as for the corresponding unit in indicating a stronger local ring current (see t-PH2 , Table 4). This can be explained by assuming that the aromatic pathway consists of a superposition of two 22p-electron pathways. In for example, the two 22 t-CH p-electron routes 2 (a), consist of six p-electrons from one aromatic pyrrolic ring with an inner hydrogen, Ðve p-electrons from the pyrrolic ring without an inner hydrogen, four p-electrons from the meso carbons, four p-electrons from the outer path of the other pyrrolic ring with an inner hydrogen, and three p-electrons from the inner path of the b-saturated pyrrolic ring. Another 22pelectron path consists of the two pyrrolic rings with an inner hydrogen, and the inner paths at the two other pyrrolic rings. For the NICS value for the pyrrolic ring without an c-CH2 , inner hydrogen is only 2.8 ppm, indicating that the inner paths at the pyrrolic rings without an inner hydrogen is the dominating one. For the chlorins with an inner hydrogen connected to the b-saturated ring, the ring current is signiÐcantly weaker than for the other chlorins. For and t-CH2 (a) c-CH2 (a), the obtained current susceptibilities are 7.4 and 7.2 nA T~1, respectively, while for the two other chlorins the corresponding values are 4.6 and 4.9 nA T~1.

Bacteriochlorins have 22p-electrons and consist of four pyrrolic rings of which two are b-saturated. The two transFig. 8 (a) The 18p-[16]annulene internal cross pathway, (b) the traditional 18p-[18]annulene pathway, (c) the most important 22pelectron pathway and (d) the 26p-electron aromatic pathway for t-PH2bacteriochlorins have large current susceptibilities, while the current susceptibility for and is 5.3 and 3.1 c-BCH2 t-IBCH2 nA T~1, respectively. The aromatic pathway for con- t-BCH2 (a) sists of two aromatic pyrrolic rings with an inner hydrogen and the inner path at the b-saturated rings yielding a 22pelectron pathway. For the pyrrolic rings without an t-BCH2 (b), inner hydrogen have large local ring currents. The aromatic pathway for consists of the two aromatic pyrrolic t-BCH2 (b) rings without an inner hydrogen and the inner paths at the b-saturated rings. Since for the current must pass t-BCH2 (b), two inner hydrogens the ring-current susceptibility is 7.8 nA T~1 as compared to 9.2 nA T~1 for has t-BCH2 (a). t-BCH2 (a) current susceptibility almost as large as It is question- t-PH2 . able whether with a current susceptibility of 3.1 nA t-IBCH2 T~1 can be considered aromatic. D. t-3BCH and 2 , t-4BCH2 t-PH2 (m) The molecules have three t-3BCH b-saturated pyrrolic rings 2 yielding 20 p-electrons. The only possible current pathway consisting of (4n ] 2) p-electrons is the 18p-[16]annulene inner cross path. The current susceptibilities for the studied t-3BCH molecules are only 2.5 and 3.3 nA T~1, respectively, 2 which indicates that they are not particularly aromatic. Energetically, lies lower than since the t-3BCH2 (a) t-3BCH2 (b), unsaturated pyrrolic ring with an inner hydrogen is much more aromatic than the pyrrolic ring without the inner hydrogen. Hence, is more stable than which t-3BCH2 (a) t-3BCH2 (b), does not have any inner hydrogen connected to the bsaturated ring. The molecules do not have a signiÐ- t-3BCH2 cant 18p-[16]annulene inner cross aromatic pathway. The current susceptibility of of 7.2 nA T t-4BCH ~1 is of 2 the same size as for and For the t-CH2 (a) c-CH2 (a). t-4BCH2 , only possible aromatic pathway is the 18p-annulene inner cross path. As expected, has a smaller ring-current t-4BCH2 radius than the other porphyrins studied. is also the t-4BCH2 only molecule among the studied ones which has a signiÐcant 18p-[16]annulene inner cross aromatic pathway. The reason is that the porphyrins in general are stabilized by the local aromaticity of the pyrrolic rings, and their aromaticity would be weakened by the 18p-[16]annulene pathway. In t-4BCH2 , all pyrrolic rings are non-aromatic and the 18p-[16]annulene aromatic pathway stabilizes the molecule energetically. In Table 2, it can be seen that is the most destabi- t-4BCH2 lized molecule as compared to the other porphyrins. Even though has a relatively strong ring current, it lies t-4BCH2 energetically high. The hydrogenation energy is 79.3 kJ mol~1 larger when two hydrogens are added to than when t-3BCH2 (a) two hydrogens are added to yielding The t-PH2 t-CH2 (a). general trend for the hydrogenation of the b-carbons for the porphyrins is that the energy gain decreases with the number of b-saturated rings. The molecule has a very large current radius, since t-PH2 (m) the two pyrrolic rings with an inner hydrogen simulate a global ring current. The saturated meso carbons prevent the global ring current, which is also reÑected on the ARCS value. From the NICS values in Table 4 one can see that the rings without an inner hydrogen are not particularly aromatic, which indicates that the pyrrolic rings without an inner hydrogen need the conjugated p-electron environment in order to sustain a local ring current. The obtained current susceptibility for is 3.0 nA T t-PH ~1, which shows that the 2 (m) contribution from the pyrrolic rings to the ARCS values of the porphyrins is in general much smaller than the contribution from the porphyrin loop. VI. Summary The present study shows that the total aromatic pathway of porphyrins must be considered as a superposition of several pathways. For porphin, all 26p-electrons are part of the aromatic pathway. The pathway must be considered mainly as a superposition of the 26p-electron path and two 22p-electron paths. For chlorins, all 24p-electrons participate in the aromatic pathway, which implies that the total aromatic pathway must be considered to consist of a superposition of 22pelectron paths. For bacteriochlorins, all 22p-electrons are involved in the aromatic pathway. The b-unsaturated pyrrolic rings in porphyrins have local ring currents which are intergraded parts of the total aromatic pathway. The current strength of the pyrrolic rings with an inner hydrogen is of about the same size as for the free pyrrole molecule. Pyrrole rings without an inner hydrogen have signiÐcantly smaller local ring currents than the rings with an inner hydrogen. The porphyrins are energetically stabilized by the aromaticity of the pyrrolic rings. The 18p-[16]annulene inner cross aromatic pathway does not exist in porphyrins until all pyrrolic rings are nonaromatic. This means that the units of the pyrrolic rings C2 H2 do not function as exocyclic bridges. We also found that the 1H NMR shieldings of the inner hydrogens correlate well with the calculated current susceptibilities, and thus can be used as an experimental measure for the aromaticity of free-base porphyrins.

Chlorin

A chlorin is a tetrapyrrole. Chlorins are partially hydrogenated versions of porphyrins.^] The parent chlorin is a rare compound, but substituted chlorins are common. Magnesium-containing chlorins are called chlorophylls. Chlorophylls are the photosensitive pigment in chloroplasts.

 Related to chlorins are bacteriochlorins and isobacteriochlorins. They are found as the core of some bacteriochlorophylls. These tetrapyrroles are further reduced (hydrogenated) relative to chlorins.

Because of their photosensitivity, chlorins are in active use as photosensitizing agents in experimental photodynamic therapy

Introduction: Drug Design, and Development

Drug design seeks to explain:
 Effects of biological compounds on the basis of molecular interaction in
terms of molecular structures or precisely the physico-chemical
properties of the molecules involved.
 Various processes by which the drugs usually produce their
pharmacological effects.
 How the drugs specifically react with the protoplasm to elicit a
particular pharmacological response.
 How the drugs usually get modified or detoxicated, metabolized or
eliminated by the organism.
 Probable relationship between biological activities with chemical
structure.

The ‘drug design’ in a broader sense implies random evaluation of synthetic as
well as natural products in bioassay systems, creation of newer drug molecules
based on biologically-active-prototypes derived from either plant or animal
kingdom, synthesis of congeners displaying interesting biological actions, the
basic concept of isosterism and bioisosterism, and finally precise design of a
drug to enable it to interact with a receptor site efficaciously.

What is a Drug

Drug is any substance presented for treating, curing or preventing disease in human beings or in animals.It may also be used for making a medical diagnosis or for restoring, correcting, or modifying physiological functions.
In medicinal chemistry, the chemist attempts to design and synthesize a
pharmaceutical agent that has a desired biological effect on the human body or
some other living system. Such a compound could also be called a 'drug', but
this is a word that many scientists dislike because society views the term with
suspicion.
With media headlines such as 'Drugs Menace’ or 'Drug Addiction Sweeps City
Streets’ this is hardly surprising.
•However, it suggests that a distinction can be drawn between drugs that are
used in medicine and drugs that are abused.
• Is this really true? Can we draw a neat line between 'good drugs' like penicillin
and 'bad drugs' like heroin?
• If so, how do we define what is meant by a good drug or a bad drug in the first
place? Where would we place a so called social drug like cannabis in this divide?
What about nicotine, or alcohol?

Medicinal chemistry unit 1 Drigs.

• Drugs – natural and synthetic alike – are chemicals used for medicinal purposes.
They interact with complex chemical systems of humans or animals.
• Medicinal chemistry is concerned with this complex interaction, focusing on the
organic and biochemical reactions of drug substances with their targets.
• Other important aspects are the synthesis and the analysis of drug substances. The
two latter aspects together are sometimes called Medicinal Chemistry, but the
synthesis of drugs is considered by some people – mainly chemists – to be part of
medicinal chemistry, denoting analytical aspects as pharmaceutical chemistry.
Objectives
The objective of Medicinal chemistry is to: Find, develop and improve drug substances that
cure or alleviate diseases and understand the causative and accompanying chemical
processes .
Medicinal chemistry is an interdisciplinary science covering a particularly wide domain
situated at the interface of organic chemistry with life sciences, such as biochemistry,
pharmacology, molecular biology, genetics, immunology, pharmacokinetics and toxicology
on one side, and chemistry-based disciplines such as physical chemistry, crystallography,
spectroscopy and computer-based techniques of simulation, data analysis and data
vis4ualization on the other side
Definition of medicinal chemistry (given by a IUPAC specialized commission)
Medicinal chemistry concerns the discovery, the development, the identification and
the interpretation of the mode of action of biologically active compounds at the
molecular level.
• Emphasis is put on drugs, but the interests of the medicinal chemist are not
restricted to drugs but include bioactive compounds in general.
• Medicinal chemistry is also concerned with the study, identification, and
synthesis of the metabolic products of various drugs and related compounds.
Medicinal chemistry is a chemistry-based discipline, involving aspects of
biological, medical and pharmaceutical sciences. It is concerned with the
invention, discovery, design, identification and preparation of biologically
active compounds, the study of their metabolism, the interpretation of their
mode of action at the molecular level and the construction of structure-
activity relationships (SARs).
Structure-activity relationship (SAR) is the relationship between chemical
structure and pharmacological activity for a series of compounds.
Lead compound is a compound that has a desirable biological activity with
therapeutic relevance, but typically has some shortcoming that is likely to be
overcome through the development of analogs.