Characteristics of organic substances

The structure of methane by pictorial representation of a Lewis diagram showing the sharing of electronpairs between atomic nuclei in a covalent bond. Please do not form the impression from the diagram that the real picture is two-dimensional, because this is not the case.

Organic compounds are generally covalently bonded. This allows for unique structures such as long carbon chains and rings. The reason carbon is excellent at forming unique structures and that there are so many carbon compounds is that carbon atoms form very stable covalent bonds with one another (catenation). In contrast to inorganic materials, organic compounds typically melt, boil, sublimate, or decompose below 300 °C. Neutral organic compounds tend to be less soluble in water compared to many inorganic salts, with the exception of certain compounds such as ionic organic compounds and low molecular weight alcohols and carboxylic acids where hydrogen bonding occurs.

Organic compounds tend to dissolve in organic solvents which are either pure substances like ether or ethyl alcohol, or mixtures, such as the paraffinic solvents such as the various petroleum ethers and white spirits, or the range of pure or mixed aromatic solvents obtained from petroleum or tar fractions by physical separation or by chemical conversion. Solubility in the different solvents depends upon the solvent type and on the functional groups if present. Solutions are studied by the science of physical chemistry. Like inorganic salts, organic compounds may also form crystals. A unique property of carbon in organic compounds is that its valency does not always have to be taken up by atoms of other elements, and when it is not, a condition termed unsaturation results. In such cases we talk about carbon carbon double bonds or triple bonds. Double bonds alternating with single in a chain are called conjugated double bonds. An aromatic structure is a special case in which the conjugated chain is a closed ring.

[edit] Molecular structure elucidation

Molecular models of caffeine

Organic compounds consist of carbon atoms, hydrogen atoms, and functional groups. The valence of carbon is 4, and hydrogen is 1, functional groups are generally 1. From the number of carbon atoms and hydrogen atoms in a molecule the degree of unsaturation can be obtained. Many, but not all structures can be envisioned by the simple valence rule that there will be one bond for each valence number. The knowledge of the chemical formula for an organic compound is not sufficient information because many isomers can exist. Organic compounds often exist as mixtures. Because many organic compounds have relatively low boiling points and/or dissolve easily in organic solvents there exist many methods for separating mixtures into pure constituents that are specific to organic chemistry such as distillation, crystallization and chromatography techniques. There exist several methods for deducing the structure an organic compound. In general usage are (in alphabetical order):

• Crystallography: This is the most precise method for determining molecular geometry; however, it is very difficult to grow crystals of sufficient size and high quality to get a clear picture, so it remains a secondary form of analysis. Crystallography has seen especially extensive use in biochemistry (for protein structure determination) and in the characterization of organometallic catalysts, which often possess significant symmetry.
• Elemental analysis: A destructive method used to determine the elemental composition of a molecule. See also mass spectrometry, below.
• Infrared spectroscopy: Chiefly used to determine the presence (or absence) of certain functional groups.
• Mass spectrometry: Used to determine the molecular weight of a compound and from the fragmentation pattern its structure. High resolution mass spectrometry can often identify the precise formula of a compound through knowledge of isotopic masses and abundances; it is thus sometimes used in lieu of elemental analysis.
• Nuclear magnetic resonance (NMR) spectrometry identifies different nuclei based on their chemical environment. This is the most important and commonly used spectroscopic technique for organic chemists, often permitting complete assignment of atom connectivity and even stereochemistry given the proper set of spectroscopy experiments (e.g. correlation spectroscopy).
• Optical rotation: Distinguishes between two enantiomers of a chiral compound based on the sign of rotation of plane polarized light. If the specific rotation of an enantiomer is known, the magnitude of rotation also gives the ratio of enantiomers in a mixed sample, though HPLC with a chiral column also can supply this information.
• UV/VIS spectroscopy: Used to determine degree of conjugation in the system. While still sometimes used to characterize molecules, UV/VIS is more commonly used to quantitate how much of a known compound is present in a (typically liquid) sample.

Additional methods are provided by analytical chemistry.

[edit] Organic reactions

Organic reactions are chemical reactions involving organic compounds. While pure hydrocarbons undergo certain limited classes of reactions, many more reactions which organic compounds undergo are largely determined by functional groups. The general theory of these reactions involves careful analysis of such properties as the electron affinity of key atoms, bond strengths and steric hindrance. These issues can determine the relative stability of short-lived reactive intermediates, which usually directly determine the path of the reaction. An example of a common reaction is a substitution reaction written as:

Nu⁻ + C-X → C-Nu + X⁻

where X is some functional group and Nu is a nucleophile.

There are many important aspects of a specific reaction. Whether it will occur spontaneously or not is determined by the Gibbs free energy change of the reaction. The heat that is either produced or needed by the reaction is found from the total enthalpy change. Other concerns include whether side reactions occur from the same reaction conditions. Any side reactions which occur typically produce undesired compounds which may be anywhere from very easy or very difficult to separate from the desired compound.

Historical highlights

Friedrich Wöhler

See also: History of chemistry

At the beginning of the nineteenth century chemists generally thought that compounds from living organisms were too complicated in structure to be capable of artificial synthesis from non-living things, and that a 'vital force' or vitalism conferred the characteristics of living beings on this form of matter. They named these compounds 'organic', and preferred to direct their investigations toward inorganic materials that seemed more promising.

Organic chemistry received a boost when it was realized that these compounds could be treated in ways similar to inorganic compounds and could be created in the laboratory by means other than 'vital force'. Around 1816 Michel Chevreul started a study of soaps made from various fats and alkali. He separated the different acids that, in combination with the alkali, produced the soap. Since these were all individual compounds, he demonstrated that it was possible to make a chemical change in various fats (which traditionally come from organic sources), producing new compounds, without 'vital force'. In 1828 Friedrich Wöhler first manufactured the organic chemical urea (carbamide), a constituent of urine, from the inorganic ammonium cyanate NH₄OCN, in what is now called the Wöhler synthesis. Although Wöhler was, at this time as well as afterwards, cautious about claiming that he had thereby destroyed the theory of vital force, most have looked to this event as the turning point.

A great next step was when in 1856 William Henry Perkin, while trying to manufacture quinine, again accidentally came to manufacture the organic dye now called Perkin's mauve, which by generating a huge amount of money greatly increased interest in organic chemistry. Another step was the laboratory preparation of DDT by Othmer Zeidler in 1874, but the insecticide properties of this compound were not discovered until much later.

The crucial breakthrough for the theory of organic chemistry was the concept of chemical structure, developed independently and simultaneously by Friedrich August Kekule and Archibald Scott Couper in 1858. Both men suggested that tetravalent carbon atoms could link to each other to form a carbon lattice, and that the detailed patterns of atomic bonding could be discerned by skillful interpretations of appropriate chemical reactions.

The history of organic chemistry continues with the discovery of petroleum and its separation into fractions according to boiling ranges. The conversion of different compound types or individual compounds by various chemical processes created the petroleum chemistry leading to the birth of the petrochemical industry, which successfully manufactured artificial rubbers, the various organic adhesives, the property-modifying petroleum additives, and plastics.

The pharmaceutical industry began in the last decade of the 19th century when acetylsalicylic acid (more commonly referred to as aspirin) manufacture was started in Germany by Bayer. The first time a drug was systematically improved was with arsphenamine (Salvarsan). Numerous derivatives of the dangerously toxic atoxyl were systematically synthesized and tested by Paul Ehrlich and his group, and the compound with best effectiveness and toxicity characteristics was selected for production.

Early examples of organic reactions and applications were serendipitous, such as Perkin's accidental discovery of Perkin's mauve. However, from the 20th century, the progress of organic chemistry allowed for synthesis of specifically selected compounds or even molecules designed with specific properties, as in drug design. The process of finding new synthesis routes for a given compounds is called total synthesis. Total synthesis of complex natural compounds started with urea, increased in complexity to glucose and terpineol, and in 1907, total synthesis was commercialized the first time by Gustaf Komppa with camphor. Pharmaceutical benefits have been substantial, for example cholesterol-related compounds have opened ways to synthesis of complex human hormones and their modified derivatives. Since the start of the 20th century, complexity of total syntheses has been increasing, with examples such as lysergic acid and vitamin B12. Today's targets feature tens of stereogenic centers that must be synthesized correctly with asymmetric synthesis.

Biochemistry, the chemistry of living organisms, their structure and interactions in vitro and inside living systems, has only started in the 20th century, opening up a brand new chapter of organic chemistry with enormous scope.

Organic chemistry information

Organic chemistry is a specific discipline within chemistry which involves the scientific study of the structure, properties, composition, reactions, and preparation (by synthesis or by other means) of chemical compounds consisting primarily of carbon and hydrogen, which may contain any number of other elements, including nitrogen, oxygen, the halogens as well as phosphorus, silicon and sulfur.[1][2] [3]

The original definition of "organic" chemistry came from the misconception that organic compounds were always related to life processes. Not only organic compounds support life on Earth, as life as we know it also depends on inorganic chemistry; for example, many enzymes rely on transition metals such as iron and copper; and materials such as shells, teeth and bones are part organic, part inorganic in composition. Apart from elemental carbon, only with certain classes of carbon compounds such as oxides, carbonates, and carbides are conventionally considered inorganic. Biochemistry deals mainly with the natural chemistry of biomolecules such as proteins, nucleic acids, and sugars.

Because of their unique properties, multi-carbon compounds exhibit extremely large variety and the range of application of organic compounds is enormous. They form the basis of, or are important constituents of many products (paints, plastics, food, explosives, drugs, petrochemicals, to name but a few) and (apart from a very few exceptions) they form the basis of all earthly life processes.

The different shapes and chemical reactivities of organic molecules provide an astonishing variety of functions, like those of enzyme catalysts in biochemical reactions of live systems. The autopropagating nature of these organic chemicals is what life is all about.

Trends in organic chemistry include chiral synthesis, green chemistry, microwave chemistry, fullerenes and microwave spectroscopy.

Antibiotic misuse

Common forms of antibiotic misuse include failure to take the entire prescribed course of the antibiotic, or failure to rest for sufficient recovery allowing clearance from the infecting organism. These practices may cause the development of bacterial populations with antibiotic resistance. Inappropriate antibiotic treatment is another common form of antibiotic misuse. A common example is the use of antibacterial antibiotics to treat viral infections such as the common cold.

[edit] Animals

It is estimated that greater than 70% of the antibiotics used in U.S. are given to feed animals (e.g. chickens, pigs and cattle) in the absence of disease.[15] Antibiotic use in food animal production has been associated with the emergence of antibiotic-resistant strains of bacteria including Salmonella spp., Campylobacter spp., Escherichia coli, and Enterococcus spp. Evidence from some US and European studies suggest that these resistant bacteria cause infections in humans that do not respond to commonly prescribed antibiotics. In response to these practices and attendant problems, several organizations (e.g. The American Society for Microbiology (ASM), American Public Health Association (APHA) and the American Medical Association (AMA)) have called for restrictions on antibiotic use in food animal production and an end to all non-therapeutic uses.[citation needed] However, delays in regulatory and legislative actions to limit the use of antibiotics are common, and may include resistance to these changes by industries using or selling antibiotics, as well as time spend on research to establish causal links between antibiotic use and emergence of untreatable bacterial diseases. Today, there are two federal bills (S.742 and H.R. 2562) aimed at phasing out non-therapeutic antibiotics in US food animal production. These bills are endorsed by public health and medical organizations including the American Nurses Association (ANA), the American Academy of Pediatrics (AAP), and the American Public Health Association (APHA).[citation needed]

[edit] Humans

One study on respiratory tract infections found "physicians were more likely to prescribe antibiotics to patients who they believed expected them, although they correctly identified only about 1 in 4 of those patients".[16] Multifactorial interventions aimed at both physicians and patients can reduce inappropriate prescribing of antibiotics. [17] Delaying antibiotics for 48 hours while observing for spontaneous resolution of respiratory tract infections may reduce antibiotic usage; however, this strategy may reduce patient satisfaction.[18]

Excessive use of prophylactic antibiotics in travelers may also be classified as misuse.

Antibiotic resistance

Main article: Antibiotic resistance

SEM depicting methicillin-resistant Staphylococcus aureus bacteria.
SEM depicting methicillin-resistant Staphylococcus aureus bacteria.

Use or misuse of antibiotics may result in the development of antibiotic resistance by the infecting organisms, similar to the development of pesticide resistance in insects. Evolutionary theory of genetic selection requires that as close as possible to 100% of the infecting organisms be killed off to avoid selection of resistance; if a small subset of the population survives the treatment and is allowed to multiply, the average susceptibility of this new population to the compound will be much less than that of the original population, since they have descended from those few organisms that survived the original treatment. This survival often results from an inheritable resistance to the compound that was infrequent in the original population, but became more frequent in the descendants.

Antibiotic resistance has become a serious problem in both the developed and underdeveloped nations. By 1984 half of the people with active tuberculosis in the United States had a strain that resisted at least one antibiotic.[citation needed] In certain settings, such as hospitals and some child-care locations, the rate of antibiotic resistance is so high that the usual, low-cost antibiotics are virtually useless for treatment of frequently seen infections. This leads to more frequent use of newer and more expensive compounds, which in turn leads to the rise of resistance to those drugs. A struggle to develop new antibiotics ensues, to prevent losing future battles against infection. To date, tuberculosis and pneumococcus are two prominent examples of once easily treated infections where drug-resistance has become a problem.
Points of attack on bacteria by antibiotics
Points of attack on bacteria by antibiotics

Another example of selection is Staphylococcus aureus ('golden staph'), which could be treated successfully with penicillin in the 1940s and 1950s. At present, nearly all strains are resistant to penicillin, and many are resistant to nafcillin, leaving only a narrow selection of drugs such as vancomycin useful for treatment. The situation is complicated by the fact that genes coding for antibiotic resistance can be transferred between bacteria via plasmids, making it possible for bacteria never exposed to an antibiotic to acquire resistance from those which have. The problem of antibiotic resistance is made more widespread when antibiotics are used to treat disorders in which they have no efficacy, such as the common cold or other viral complaints, and when they are used broadly as prophylaxis rather than treatment (as in, for example, animal feeds), because this exposes more bacteria to selection for resistance.

[edit] Resistance modifying agents

One solution to combat resistance currently being researched is the development of pharmaceutical compounds that would revert multiple antibiotic resistance. These so called resistance modifying agents may target and inhibit MDR mechanisms rendering the bacteria susceptible to antibiotics they were previously resistant to. These compounds targets include among others

* Efflux inhibition(Phe-Arg-β-naphthylamide)[19]
* Beta Lactamase inhibitors - Including Clavulanic acid and Sulbactam

[edit] Beyond antibiotics

The comparative ease of identifying compounds which safely cured bacterial infections was more difficult to duplicate in treatments of fungal and viral infections. Antibiotic research led to great strides in the knowledge of biochemistry, establishing large differences between the cellular and molecular physiology of the bacterial cell and that of the mammalian cell. This explained the observation that many compounds that are toxic to bacteria are non-toxic to human cells. In contrast, the basic biochemistries of the fungal cell and the mammalian cell are much more similar. This restricts the development and use of therapeutic compounds that attack a fungal cell, while not harming mammalian cells. Similar problems exist in antibiotic treatments of viral diseases. Human viral metabolic biochemistry is very closely similar to human biochemistry, and the possible targets of antiviral compounds are restricted to very few components unique to a mammalian virus.

Research into bacteriophages for use as antibiotics is presently ongoing. Several types of bacteriophage appear to exist that are specific for each bacterial taxonomic group or species.[citation needed] Research into bacteriophages for medicinal use is just beginning, but has led to advances in microscopic imaging.[20] While bacteriophages provide a possible solution to the problem of antibiotic resistance, there is no clinical evidence yet that they can be deployed as therapeutic agents to cure disease.

Phage therapy has been used in the past on humans in the US and Europe during the 1920s and 1930s, but these treatments had mixed results. With the discovery of penicillin in the 1940s, Europe and the US changed therapeutic strategies to using antibiotics. However, in the former Soviet Union phage therapies continued to be studied. In the Republic of Georgia, the Eliava Institute of Bacteriophage, Microbiology & Virology continues to research the use of phage therapy. Various companies and foundations in North America and Europe are currently researching phage therapies.[citation needed] However, phage are living and reproducing; concerns about genetic engineering in freely released viruses currently limit certain aspects of phage therapy.

Bacteriocins are also a growing alternative to the classic small-molecule antibiotics [21]. Different classes of bacteriocins have different potential as therapeutic agents. Small molecule bacteriocins (microcins, for example, and lantibiotics) may be similar to the classic antibiotics; colicin-like bacteriocins are more likely to be narrow-spectrum, demanding new molecular diagnostics prior to therapy but also not raising the specter of resistance to the same degree. One drawback to the large molecule antibiotics is that they will have relative difficulty crossing membranes and travelling systemically throughout the body. For this reason, they are most often proposed for application topically or gastrointestinally[22]. Because bacteriocins are peptides, they are more readily engineered than small molecules[23]. This may permit the generation of cocktails and dynamically improved antibiotics that are modified to overcome resistance.

Probiotics are another alternative that goes beyond traditional antibiotics by employing a live culture which may establish itself as a symbiont, competing, inhibiting, or simply interfering with colonization by pathogens. It may produce antibiotics or bacteriocins, essentially providing the drug in vivo and in situ, potentially avoiding the side effects of systemic administration.

History

Penicillin

Although potent antibiotic compounds for treatment of human diseases caused by bacteria (such as tuberculosis, bubonic plague, or leprosy) were not isolated and identified until the twentieth century, the first known use of antibiotics was by the ancient Chinese over 2,500 years ago.^[1] Many other ancient cultures, including the ancient Egyptians and ancient Greeks already used molds and plants to treat infections, owing to the production of antibiotic substances by these organisms, a phenomenon known as antibiosis^[2] Antibiosis was first described in 1877 in bacteria when Louis Pasteur and Robert Koch observed that an airborne bacillus could inhibit the growth of Bacillus anthracis.^[3] The antibiotic properties of Penicillium sp. were first described in France by Ernest Duchesne in 1897. However, his work went by without much notice from the scientific community until Alexander Fleming's discovery of Penicillin (see below).

Modern research on antibiotic therapy began in Germany with the development of the narrow-spectrum antibiotic Salvarsan by Paul Ehrlich in 1909, for the first time allowing an efficient treatment of the then-widespread problem of Syphilis. The drug, which was also effective against other spirochaetal infections, is no longer in use in modern medicine.

Antibiotics were further developed in Britain following the re-discovery of Penicillin in 1928 by Alexander Fleming. In 1939, Rene Dubos isolated gramicidin, one of first antibiotics to be manufactured commercially used during World War II proving highly effective in the treatment of wounds and ulcers.^[4] More than ten years later, Ernst Chain and Howard Florey became interested in his work, and came up with the purified form of penicillin. The three shared the 1945 Nobel Prize in Medicine. Howard credited Dubos for reviving his research on penicillin^[4]

"Antibiotic" was originally used to refer only to substances extracted from a fungus or other microorganism, but has come to also include the many synthetic and semi-synthetic drugs that have antibacterial effects. Antibiotics can help succeed in curing many illnesses

Antibiotic - what is this?

An antibiotic is a chemotherapeutic agent that inhibits or abolishes the growth of micro-organisms, such as bacteria, fungi, or protozoa. The term originally referred to any agent with biological activity against living organisms; however, "antibiotic" now is used to refer to substances with anti-bacterial, anti-fungal, or anti-parasitical activity. The first widely used antibiotic compounds used in modern medicine were produced and isolated from living organisms, such as the penicillin class produced by fungi in the genus Penicillium, or streptomycin from bacteria of the genus Streptomyces. With advances in organic chemistry many antibiotics are now also obtained by chemical synthesis, such as the sulfa drugs. Many antibiotics are relatively small molecules with a molecular weight less than 2000 Da.