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chemical structure of hesperidin

2023-09-27



1. Chemical Structure Overview

1. Chemical Structure Overview

Hesperidin is a naturally occurring flavonoid glycoside found predominantly in citrus fruits, particularly in the peels and membranes. It is known for its various biological activities and health benefits, which include antioxidant, anti-inflammatory, and anticancer properties. The chemical structure of hesperidin is intricate and consists of several components that contribute to its unique properties.

At the core of hesperidin's structure is the flavanone aglycone, hesperetin, which is a type of flavonoid. Hesperetin itself is a derivative of flavanone, with a basic structure that includes a 2-phenylchromen-4-one backbone. This backbone consists of a benzene ring (A ring) attached to a heterocyclic pyran ring (C ring) through a three-carbon chain.

Hesperidin is a glycoside of hesperetin, where the 7-hydroxyl group of the A ring is glycosidically linked to a rhamnose sugar. This rhamnose is further linked to a glucose molecule, forming a disaccharide. The presence of these sugar moieties increases the water solubility of hesperidin, which is important for its bioavailability and absorption in the body.

The chemical structure of hesperidin can be represented by the following general formula:

C28H34O15

This formula indicates that hesperidin is composed of 28 carbon atoms, 34 hydrogen atoms, and 15 oxygen atoms, arranged in a specific configuration that defines its molecular structure and properties.

In summary, the chemical structure of hesperidin is characterized by a flavanone aglycone core, hesperetin, to which a disaccharide unit consisting of rhamnose and glucose is attached. This structure is responsible for the diverse biological activities and potential health benefits associated with hesperidin. Understanding the chemical structure of hesperidin is crucial for exploring its applications in medicine, nutrition, and pharmaceuticals.



2. Molecular Formula and IUPAC Name

2. Molecular Formula and IUPAC Name

Hesperidin is a flavanone glycoside, which is a type of flavonoid. Its molecular formula is C28H34O15, indicating that it consists of 28 carbon atoms, 34 hydrogen atoms, and 15 oxygen atoms. The IUPAC name for hesperidin is 4',5,7-trihydroxy-3'-[(6-O-α-L-rhamnopyranosyl-β-D-glucopyranosyl)oxy]flavanone. This name reflects the specific arrangement and connectivity of the atoms within the molecule, as well as the presence of functional groups such as hydroxyl groups and glycosidic linkages.

The IUPAC name provides a detailed description of the molecule's structure, including the positions of the hydroxyl groups (4', 5, and 7) and the nature of the glycosidic linkages (α-L-rhamnopyranosyl and β-D-glucopyranosyl). The numbers in the name refer to the specific carbon atoms in the flavanone backbone to which the functional groups are attached.

In addition to its IUPAC name, hesperidin is also commonly referred to by its trivial name, which is derived from the source plant, Hesperidin, where it was first isolated. The trivial name is more colloquial and easier to remember, but the IUPAC name provides a more precise and standardized way to describe the molecule's structure.

Understanding the molecular formula and IUPAC name of hesperidin is important for accurately describing its chemical properties and for distinguishing it from other similar compounds. This information is also crucial for researchers and chemists who are studying the synthesis, isolation, and biological activity of hesperidin and related compounds.



3. Functional Groups and Bonding

3. Functional Groups and Bonding

Hesperidin is a flavanone glycoside, which means it is a type of flavonoid with a specific sugar molecule attached. The chemical structure of hesperidin is characterized by the presence of several functional groups and bonding patterns that contribute to its unique properties and biological activities.

1. Flavanone Core: The core structure of hesperidin is a flavanone, which is a type of flavonoid. Flavanones are characterized by a 15-carbon skeleton that includes three six-membered rings (A, B, and C) and a five-membered ring (D). The flavanone core of hesperidin has a double bond between carbons 2 and 3 (C2=C3), which is a key feature of flavonoids.

2. Hydroxyl Groups: Hesperidin contains multiple hydroxyl groups (-OH) attached to the flavanone core. These hydroxyl groups are found at positions 5, 7, 4', and 3' on the A, B, and C rings, respectively. The presence of these hydroxyl groups allows hesperidin to form hydrogen bonds, which can influence its solubility, stability, and interactions with other molecules.

3. Rhamnosyl and Glucosyl Moieties: Hesperidin is a glycoside, which means it has sugar molecules attached to its core structure. Specifically, hesperidin has a rhamnosyl (6-deoxyhexose) moiety attached to the 7-OH group of the flavanone core, and a glucosyl (hexose) moiety attached to the 6-OH group of the rhamnosyl moiety. The attachment of these sugar moieties is through glycosidic linkages, which are formed by the reaction of the anomeric carbon of the sugar with a hydroxyl group of the aglycone (in this case, the flavanone core).

4. Glycosidic Bonds: The glycosidic bonds in hesperidin are β-1,2 linkages, which means that the glycosidic oxygen is attached to the second carbon of the rhamnose, and the rhamnose is attached to the 7-OH group of the flavanone core. The β-1,6 linkage connects the glucose to the rhamnose. These specific types of glycosidic bonds are important for the stability and biological activity of hesperidin.

5. Aromatic Rings: The A and B rings of the flavanone core are aromatic, meaning they are planar and have delocalized π-electron systems. This aromaticity contributes to the stability of the molecule and can influence its reactivity and interactions with other molecules.

6. Conjugated Double Bonds: The double bond between carbons 2 and 3 in the flavanone core is part of a conjugated system with the carbonyl group at position 4. This conjugation can influence the molecule's UV-Vis absorption properties and its reactivity.

The functional groups and bonding in hesperidin are crucial for its biological activities, such as its antioxidant, anti-inflammatory, and vasodilatory effects. Understanding these structural features is essential for the development of new compounds with improved pharmacological properties and for the optimization of extraction and synthesis techniques.



4. Stereochemistry and Conformation

4. Stereochemistry and Conformation

Hesperidin, a flavanone glycoside, exhibits a complex chemical structure that includes multiple stereocenters and conformations. The stereochemistry of hesperidin is crucial for its biological activity and interactions with biological targets.

4.1 Stereocenters
Hesperidin contains several stereocenters, which are carbon atoms bonded to four different groups. The presence of stereocenters leads to the formation of enantiomers and diastereomers. The stereochemistry of hesperidin is essential for its biological activity, as different stereoisomers may exhibit different levels of activity or even antagonistic effects.

4.2 Conformational Analysis
The conformation of hesperidin is influenced by the arrangement of its functional groups and the nature of the chemical bonds. The flavanone core of hesperidin adopts a specific conformation that allows for optimal interactions with other molecules. The glycosidic linkages between the flavanone core and the sugar moieties also contribute to the overall conformation of hesperidin.

4.3 Conformational Flexibility
Hesperidin exhibits conformational flexibility due to the presence of rotatable bonds, such as the C-O and C-C bonds in the sugar moieties. This flexibility allows hesperidin to adopt different conformations, which may be important for its interactions with biological targets and its overall biological activity.

4.4 Stereoselective Synthesis
The stereoselective synthesis of hesperidin is an important aspect of its production and characterization. The development of stereoselective synthetic methods allows for the preparation of specific stereoisomers of hesperidin, which can be used to study the relationship between stereochemistry and biological activity.

4.5 Stereochemistry in Biological Activity
The stereochemistry of hesperidin plays a significant role in its biological activity. Different stereoisomers of hesperidin may exhibit different levels of activity or even different types of activity. Understanding the relationship between stereochemistry and biological activity can help guide the development of more effective and selective hesperidin-based therapeutic agents.

In conclusion, the stereochemistry and conformation of hesperidin are critical factors that influence its biological activity and interactions with biological targets. Further research into the stereochemistry of hesperidin and its impact on biological activity will be essential for the development of more effective hesperidin-based therapeutic agents.



5. Synthesis and Isolation Techniques

5. Synthesis and Isolation Techniques

Hesperidin, a naturally occurring flavanone glycoside, is primarily found in citrus fruits, particularly in the peels of oranges and lemons. The synthesis and isolation of hesperidin can be achieved through various techniques, which are essential for understanding its chemical properties and potential applications in pharmaceutical and food industries.

5.1 Extraction Methods

The most common method for isolating hesperidin from natural sources is through extraction. This process can be carried out using solvents such as water, ethanol, or methanol. The choice of solvent depends on the desired purity and yield of hesperidin. The extraction process typically involves the following steps:

1. Preparation of Plant Material: The citrus peels are cleaned, dried, and ground into a fine powder.
2. Solvent Selection: A suitable solvent is chosen based on the solubility of hesperidin.
3. Extraction: The powdered material is mixed with the solvent and allowed to soak for a specific period.
4. Filtration: The mixture is filtered to separate the solid residue from the liquid extract.
5. Concentration: The liquid extract is then concentrated to obtain a hesperidin-rich solution.
6. Purification: Further purification steps, such as chromatography, may be employed to remove impurities and isolate hesperidin.

5.2 Synthesis Approaches

Although hesperidin is abundant in nature, synthetic methods have been developed to produce it in the laboratory. These methods are useful for studying its chemical properties and for applications where natural sources may be limited. Some of the synthetic approaches include:

1. Chemical Synthesis: This involves the stepwise assembly of the hesperidin molecule from smaller organic compounds. The process requires careful control of reaction conditions to ensure the correct formation of functional groups and stereochemistry.
2. Enzymatic Synthesis: Enzymes can be used to catalyze the formation of glycosidic bonds between aglycones and sugar moieties, leading to the synthesis of hesperidin. This method is advantageous due to its mild reaction conditions and high selectivity.
3. Biosynthesis: Genetic engineering techniques can be employed to produce hesperidin in microorganisms or plant cell cultures. This approach has the potential to scale up production and reduce the reliance on natural sources.

5.3 Analytical Techniques

The synthesis and isolation of hesperidin can be monitored and confirmed using various analytical techniques, such as:

1. High-Performance Liquid Chromatography (HPLC): This technique is widely used for the separation and quantification of hesperidin in complex mixtures.
2. Mass Spectrometry (MS): MS provides information on the molecular weight and structural features of hesperidin, which can be used to confirm its identity.
3. Nuclear Magnetic Resonance (NMR) Spectroscopy: NMR can be used to study the chemical structure and stereochemistry of hesperidin in detail.
4. Infrared (IR) Spectroscopy: IR spectroscopy can provide information on the functional groups present in hesperidin.

5.4 Challenges and Optimization

The synthesis and isolation of hesperidin face several challenges, including:

1. Low Yield: The extraction process may result in low yields of hesperidin, especially when using water as a solvent.
2. Impurities: The presence of other compounds in the extract can complicate the purification process.
3. Stability: Hesperidin may degrade under certain conditions, such as high temperatures or exposure to light.

To overcome these challenges, researchers are continuously working on optimizing extraction and synthesis methods to improve yield, purity, and stability. This includes the development of novel solvent systems, enzymatic approaches, and advanced purification techniques.

In conclusion, the synthesis and isolation of hesperidin are crucial for understanding its biological activity and potential applications. Various techniques, including extraction, chemical synthesis, enzymatic synthesis, and biosynthesis, have been developed to obtain hesperidin from natural sources or to produce it in the laboratory. Analytical methods play a vital role in monitoring and confirming the synthesis and isolation process, while ongoing research aims to address the challenges associated with yield, purity, and stability.



6. Biological Activity and Applications

6. Biological Activity and Applications

Hesperidin, a flavanone glycoside, is known for its wide range of biological activities and applications in various fields of medicine, nutrition, and cosmetics. Its beneficial effects are attributed to its antioxidant, anti-inflammatory, and antimicrobial properties, among others.

Antioxidant Activity:
Hesperidin exhibits strong antioxidant properties, which help in neutralizing free radicals and preventing oxidative stress. This activity is crucial in protecting cells from damage that can lead to various diseases, including cancer, cardiovascular diseases, and neurodegenerative disorders.

Anti-Inflammatory Effects:
The anti-inflammatory properties of hesperidin are beneficial in reducing inflammation and alleviating symptoms associated with inflammatory conditions such as arthritis and asthma. It is believed to modulate the activity of inflammatory mediators, thereby reducing the inflammatory response.

Antimicrobial Properties:
Hesperidin has been shown to possess antimicrobial activity against a variety of pathogens, including bacteria, fungi, and viruses. This makes it a potential candidate for the development of natural antimicrobial agents, which can be used in the treatment of infections and as preservatives in food products.

Cardiovascular Health:
Hesperidin has been linked to the improvement of cardiovascular health by reducing blood pressure, improving blood flow, and lowering cholesterol levels. Its vasodilatory effects can help in the prevention of atherosclerosis and other cardiovascular diseases.

Diabetes Management:
Studies have suggested that hesperidin may help in managing diabetes by improving insulin sensitivity and reducing blood glucose levels. This can be particularly beneficial for individuals with type 2 diabetes.

Cosmetic Applications:
Due to its antioxidant and anti-inflammatory properties, hesperidin is used in the cosmetic industry for skin care products. It can help in reducing skin inflammation, promoting collagen synthesis, and protecting the skin from environmental damage.

Nutritional Supplements:
Hesperidin is often included in nutritional supplements for its health-promoting properties. It can be found in formulations aimed at improving cardiovascular health, supporting the immune system, and enhancing overall well-being.

Future Applications:
As research continues, the potential applications of hesperidin may expand. It is currently being studied for its possible role in the treatment of various cancers, as well as its potential to improve cognitive function and delay the aging process.

In summary, hesperidin's diverse biological activities make it a valuable compound for both therapeutic and preventive health applications. Its integration into various products and treatments highlights the significance of natural compounds in modern healthcare and wellness practices.



7. Pharmacokinetics and Metabolism

7. Pharmacokinetics and Metabolism

Pharmacokinetics is the study of how a drug or other substance is absorbed, distributed, metabolized, and excreted by the body. In the case of hesperidin, understanding its pharmacokinetics and metabolism is crucial for evaluating its bioavailability, efficacy, and safety as a dietary supplement or therapeutic agent.

Absorption:
Hesperidin is a flavanone glycoside that is poorly absorbed in its native form in the gastrointestinal tract. The absorption rate can be influenced by various factors, including the presence of other dietary components and the individual's gut microbiota. Once ingested, hesperidin is often hydrolyzed by enzymes in the gut, such as β-glucosidase, to release hesperetin, which is more bioavailable and can be absorbed into the bloodstream.

Distribution:
After absorption, hesperetin, the aglycone form of hesperidin, is distributed throughout the body. It has been found to cross the blood-brain barrier, indicating potential central nervous system effects. Hesperetin can also bind to plasma proteins, which may influence its distribution and half-life in the body.

Metabolism:
Hesperetin undergoes phase II metabolism in the liver, where it is conjugated with glucuronic acid or sulfate to form metabolites such as hesperetin-7-O-glucuronide and hesperetin-3'-O-sulfate. These conjugated forms are more water-soluble and can be more easily excreted by the body. The metabolism of hesperetin can also involve other pathways, including methylation and reduction, depending on the individual's metabolic profile and the presence of specific enzymes.

Excretion:
The metabolites of hesperidin are primarily excreted in the urine and, to a lesser extent, in the feces. The rate of excretion can vary depending on the individual's metabolic rate, kidney function, and the presence of other substances that may affect the elimination process.

Factors Affecting Pharmacokinetics:
Several factors can influence the pharmacokinetics of hesperidin, including:

- Dosage and Formulation: The amount of hesperidin ingested and its formulation (e.g., as a supplement or in food) can affect its absorption and bioavailability.
- Gastrointestinal Microbiota: The composition and activity of the gut microbiota play a significant role in the hydrolysis of hesperidin to hesperetin.
- Genetic Variability: Individual genetic differences in the expression of enzymes involved in the metabolism and transport of hesperidin can affect its pharmacokinetics.
- Dietary Interactions: The presence of other dietary components, such as fiber or fat, can influence the absorption and metabolism of hesperidin.

Clinical Implications:
Understanding the pharmacokinetics and metabolism of hesperidin is essential for optimizing its therapeutic use. It can help in determining the appropriate dosage, frequency of administration, and potential interactions with other medications or dietary components. Additionally, knowledge of its metabolism can inform the development of prodrugs or analogs with improved bioavailability and pharmacological properties.

Future Research:
Further research is needed to elucidate the specific enzymes and transporters involved in the absorption, distribution, metabolism, and excretion of hesperidin. This knowledge could lead to the development of strategies to enhance its bioavailability and therapeutic efficacy. Additionally, studies on the pharmacokinetics of hesperidin in different populations, such as the elderly or those with specific health conditions, could provide valuable insights for personalized medicine approaches.



8. Safety and Toxicity Considerations

8. Safety and Toxicity Considerations

Hesperidin, a flavonoid glycoside commonly found in citrus fruits, has been widely studied for its potential health benefits. However, as with any substance, it is important to consider its safety and potential toxicity.

8.1 General Safety Profile
Hesperidin is generally recognized as safe (GRAS) by the U.S. Food and Drug Administration (FDA). It is commonly consumed in the diet through citrus fruits without any reported adverse effects. However, it is important to note that the safety profile of hesperidin in its pure form or as a dietary supplement may differ from its consumption in food.

8.2 Potential Side Effects
While hesperidin is considered safe for most individuals, some potential side effects have been reported, particularly at high doses. These may include gastrointestinal issues such as diarrhea, abdominal pain, and nausea. Allergic reactions, although rare, are also possible.

8.3 Toxicity Studies
Limited studies have been conducted on the toxicity of hesperidin. However, no significant toxic effects have been observed in animal studies at doses relevant to human consumption. Further research is needed to fully understand the potential toxic effects of hesperidin, especially at high doses or in specific populations.

8.4 Interactions with Medications
Hesperidin may interact with certain medications, particularly those metabolized by the liver. It is important for individuals taking medications to consult with their healthcare provider before supplementing with hesperidin.

8.5 Pregnancy and Lactation
The safety of hesperidin during pregnancy and lactation has not been well-studied. As a precaution, it is recommended that pregnant and breastfeeding women avoid supplementing with hesperidin or consume it in moderation through dietary sources.

8.6 Conclusion
While hesperidin is generally considered safe for consumption, it is important to be aware of potential side effects and interactions with medications. Further research is needed to fully understand its safety profile, particularly at high doses or in specific populations. As always, moderation and consultation with a healthcare provider are key when considering the use of dietary supplements.



9. Future Research Directions

9. Future Research Directions

As our understanding of hesperidin and its potential applications continues to grow, several areas of research present themselves as promising avenues for future investigation. Here are some key directions that could be explored:

9.1 Advanced Synthesis Techniques
Developing new and efficient methods for the synthesis of hesperidin could lead to increased availability and affordability of this compound for research and therapeutic applications. This could involve exploring novel enzymatic or biocatalytic processes, as well as green chemistry approaches that minimize environmental impact.

9.2 Mechanistic Studies
Further elucidation of the molecular mechanisms by which hesperidin exerts its biological effects is crucial. This includes understanding its interactions with various cellular receptors, signaling pathways, and its role in modulating gene expression.

9.3 Structure-Activity Relationship (SAR) Studies
Investigating the relationship between the chemical structure of hesperidin and its biological activity can help in the design of more potent and selective analogs. This could involve the synthesis and testing of various hesperidin derivatives to identify structural features that enhance or inhibit specific activities.

9.4 Drug Delivery Systems
Research into innovative drug delivery systems for hesperidin could improve its bioavailability and therapeutic efficacy. This might involve the development of nanoparticles, liposomes, or other carriers that protect hesperidin from degradation and facilitate its targeted delivery to tissues or cells.

9.5 Clinical Trials
Conducting well-designed clinical trials to assess the safety, efficacy, and optimal dosing of hesperidin in various disease conditions is essential. This will provide valuable data to support its use in clinical practice and guide the development of new formulations.

9.6 Metabolomics and Systems Biology
Utilizing metabolomics and systems biology approaches to study the effects of hesperidin on the global metabolic profile and biological networks can reveal new insights into its mode of action and potential off-target effects.

9.7 Combination Therapy
Exploring the potential of hesperidin in combination with other drugs or natural products could lead to synergistic effects and improved therapeutic outcomes. This requires a thorough understanding of the interactions between hesperidin and other compounds at the molecular level.

9.8 Personalized Medicine
Investigating the role of genetic and epigenetic factors in modulating the response to hesperidin could pave the way for personalized medicine approaches, where treatment is tailored to an individual's unique genetic makeup.

9.9 Environmental and Agricultural Applications
Research into the potential use of hesperidin in agriculture, such as its role in plant defense mechanisms or as a natural pesticide, could have significant implications for sustainable farming practices.

9.10 Computational Modeling
Employing computational chemistry and molecular modeling techniques to predict the behavior of hesperidin in various biological contexts can complement experimental studies and guide the design of new experiments.

By pursuing these research directions, the scientific community can deepen its understanding of hesperidin, optimize its therapeutic potential, and expand its applications in medicine, agriculture, and other fields.

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