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Earth Air Fire and Water Introduction. The image on the left is a very early model manufactured by a company called Gallenkamp and gives a fair idea of the principles. The analysers of today are considerably more sophisticated and cost a great deal of money. A natural substance will produce a characteristic rotation signature which is used for identification purposes when examining a sample. The concept, of a shape of a molecule in space, helps us to understand why synthetic molecules, wreak so much damage and disruption, when taken into a structure composed of natural molecules. Stereo Chemistry
7.23 Stereo chemistry deals with the structure of molecules and the position of the molecular atoms in 3 dimensional space. Therefore, we have the further concept of Stereo-isomerism, in which the isomers have the same formula and functional groups, but the atoms are arranged differently in space, which also results in different properties. Stereo isomers govern most of the reactions that occur in a living system. Structural Representation
7.24 Molecular geometry is a means of studying the manner in which atoms arrange themselves around a polyvalent central atom, and then the further concept of bond angles. It has already been stated that Carbon is tetravalent, i.e., forms 4 bonds. It has been determined that the Hydrogen bond angles are 109.5� which means that a molecule of methane will have the geometry of a tetrahedron as follows. Figure 7.24A All carbon atoms that have 4 single bonds will have a tetrahedral structure, e.g. Chloroform (CHCl3). Most bond angles are constant enough to be considered normal for a particular atom and its state of valence, 1. Water (H2O) Bond angle 105� 2. Ammonia (H3N) Bond angle 107� 3. Hydrogen sulphide (H2S) Bond angle 92� Molecules and Mirrors 7.25 1. Those that may be super imposed on each other, e.g. The rules of the game state, that for an object to be super imposable on its mirror image, it is permissible to slide one across the other, such as a circle or a square; or if the mirror image is rotated through 180� and a match is made, then the object is symmetrical. In Figure 7.25A, molecule 2 is the reflected image of molecule 1. If molecule 2 is rotated through 180� it will have the same geometry as molecule 3. Molecule 3 is then identical to (super imposable) molecule 1. Any molecule that meets that criterion is called an Achiral molecule, irrespective of its structure. 2. Mirror images that cannot be superimposed on each other are said to be Chiral (ky-ral). The word chiral is from the Greek �chier� meaning �hand�. For example, hold your right hand up to a mirror, palm forward, the mirror image that you see is that of the left hand. Compare the palm of your left hand with the image in the mirror. Such structures are asymmetrical or chiral. Enantiomers 7.26 Chiral molecules will react in the same manner as Achiral molecules, i.e. Enantiomers will have the same physical and chemical properties, however the rate of reaction differs which gives them different biological properties and they also differ in optical activity. The �R� and �S� Convention
7.27 An added advantage of this system is, that a chemist, by prefixing the name of a compound with an �R� or �S�, can indicate the arrangement, of the four different groups, around a chiral carbon. To make use of the system the groups around the central carbon are assigned a priority according to their respective atomic numbers. The greater the number, the higher the order of priority. The atom or group with the lowest priority, i.e. the lowest atomic number, is placed behind the chiral center. The atom or group with the highest priority, i.e. number one is placed at the top. From this position if the next highest priority falls to the right of the chiral center, i.e. a clockwise direction, it is an �R� stereo isomer and if to the left, it is the �S� form, Figure 7.27A
The shaded area represents the atom or group which has the lowest priority
In para.7.26 it was stated that the (R) and (S) forms of an Enantiomeric pair have different rates of reaction and exhibit different biological behavior, for example, it is known that the (S) form of the alkaloid nicotine has a greater toxicity than the (R) form. The (R) and (S) form of some artificial sweeteners is also detectable. A further much quoted example is that of Carvone, which a naturally occurring constituent of many umbelliferous plants is. The (R) and (S) forms have different odors. Figure 7.27B Many enzymes are known to be stereo specific, they will interact with one form and not the other. This fact alone should send shudders down ones spine and it offers a further explanation of the huge increase in disease and mortality of mankind. The plants that we use for food and medicine have balanced R and S structures. The synthetics which have been introduced for flavours cosmetics and medicines do not. Even when the chemist knows which is the preferred form, they are not able to resolve the mix which they have constructed. The havoc and damaged that this has caused is beyond dispute. The synthetic mirror images in many cases passes straight the the walls of the intestines where as the natural substance if harmful would be blocked. The folic acid situation is a case in point. Optical Activity 7.28
Not surprisingly, the evidence for molecular geometry started to accumulate in the area of crystallography. Suffice to say, that in 1815 the French physicist J.B. Biot demonstrated that natural organic compounds, whether liquid, or in solution, rotated the plane of polarized light to a greater or lesser degree depending on the substance. Such substances were said to be Optically Active. Polarised Light 7.29 Figure 7.29A When an optically active substance is placed in the path of a beam of polarized light, the beam will be deflected, or to use the correct term, it will be rotated. The angle of the deflection is noted and it is called the �Observed Rotation�. The Polarimeter 7.30 The Polarimeter is the device that is used to study and identify optically active substances. Fig 7.30A
The apparatus is enclosed in a tube which has a port incorporated for the insertion or removal of the substance to be investigated. The Polarimeter must first be calibrated, the procedure is simple. With the Polarimeter empty, the light is turned on and an observation made. If light is observed the analyzer lens is rotated until the light is blocked and the field of view is dark. The reading is taken from a scale usually attached to the Analyser lens. A number of readings may needed. Especially if the instrument is of an older type. This position of dark field is as represented in figure 7.29A A liquid sample of the substance to be investigated, commonly called the cell, is inserted into the body of the Polarimeter. If the sample is optically active it will alter the polarization of the light and it will pass through the analyzer lens, as represented in diagram �A� Figure 7.29A. To ensure accuracy, several readings of the observed rotation must be made. The analyzer lens is rotated until the field of view shows maximum light intensity. From that position the analyzer is rotated until the light is blocked and the field of view is once again dark. If the analyzer must be rotated to the left to restore the dark field, the optically active substance is said to be Levorotatory , and if to the right, Dextrorotatory. Figure 7.30B If the substance under examination does not pass light through the analyzer lens, and the field of view remains dark, the substance is said to be Optically Inactive. The Racemate 7.31 The term is from the Latin �rac�mus�, meaning �bunch of grapes�. Racemic acid is an isomeric modification of Tartaric acid which is often found in grape juice. The term Racemisation means the conversion of an optically active substance into an optically inactive substance. Any enzyme which will catalyze the conversion of an optically active into an optically inactive compound is known as a �Racemase�. Chirality and Biological Systems
7.32 D-glucose is used to power bodily functions in humans, without it we could not exist. Science does not know how to create optically active substances, although they can propagate chirality by borrowing from nature. However, as stated previously such procedures have led us to the brink of disaster. Chirality and Synthetic Drugs
7.33 Lethal Racemates 7.34 The sort of problems found with the racemates are not confined to the prescription only drugs. The over the counter (OTC�s) drugs and pharmacy only medications (POM�s) are generally considered to be safe and yet, the ubiquitous Aspirin is estimated to be responsible for around 5% of fatal poisonings each year. The much used anti-inflammatory, antacids and laxatives are estimated to account for 20% of all drug related hospital admissions. The major point to be made is, that many of the drugs implicated in fatalities and extreme reactions had been on the market for a number of years before being withdrawn. Given the evidence surrounding the synthetic and semi-synthetic drugs, the problem must only represent a small percentage of the total. The Herb as Manufacturing Herbalist
7.35 Figure 7.35A For the purpose of clarity figure 7.35A is a very simply representation. Each division is responsible for many compounds of great complexity. For example, Chlorophyll is the major pigment involved in the photosynthetic process. Its structural representation is as follows; Figure 7.35B
It will be seen that the head of the chlorophyll is a complex ring structure which contains many carbon, carbon double bonds, which are very reactive. The head is the receptor site for in coming solar energy. The long carbon tail is embedded, or anchored in a special type of cell called a chloroplast. Photosynthesis is sometimes described as a reverse respiration process, carbon dioxide is taken in and oxygen is given out. In that respect it is interesting to note the similarity of structure between haemoglobin, which carries oxygen to the tissues of humans, and that of plant chlorophyll. Haemoglobin contains iron (Fe) at the center of its ring structure instead of Mg and contains two extra nitrogen atoms. From the point when the first leaf shoot of an embryo plant, commence to photosynthesize, a great cascade of biochemical reactions are set in motion supreme alchemy and transmutation at bio temperatures. At low bio temperatures, and at great speed, many thousands of intricate compounds are constructed. Some are for immediate use and some for storage, while many others are precursors of further synthesis. Amino acids, enzymes, hormones, nucleic acids, steroids, vitamins, all in great profusion, and unlike the pharmaceutical synthetics that can only provoke a single pharmaceutical response, medications based on the whole plant not only act synergistically, but the action is bolstered with nutritional supplements. The plant compounds are the same as, or very similar to those found in the human body. In 1970, Lynn Margulis at Boston University, caused an uproar when she advanced the view that the cells of the higher organisms, the eukaryotes, began as communities of prokaryotes, which are single celled organisms. That strongly suggests common ancestry for all life forms, i.e., evolution by division and symbiosis. However, just like the anthropoid theory, it is anybodies guess because we are talking about a timescale of at least 600 million years.
One perceives the fundamental essence of life in the living, not the inanimate, in that which is changing, not in what is finished. Goethe. -::-::-
Acids, Bases and Salts 7.36 Acids 7.37 1. In the pure form they are non-electrolytes, they do not conduct electricity, if dissolved in water they will. 2. They contain hydrogen atoms. 3. They react with alkali or bases to form salts and water. 4. They will react with carbonates to form salts, carbon dioxide and water. When a non metallic element combines with oxygen, the oxide formed is usually gaseous. If the gas is combined with water, then an acid is formed. Bases and Alkalis 7.38 In all things you
shall find everywhere the Acid and the Alcaly. Figure 7.38A
When acid and base are combined in the correct proportion, neutralization occurs and the product is a salt. The type of salt formed will obviously depend upon the type of reactants and the composition of the solvent. Strong acids and bases result in a fast reaction time; with weak acids and bases, the reaction may be spread over a number of weeks, and therefore go unnoticed, which if alkaloidal salts were being precipitated in plant preparations and where the wrong solvent is used then, it could have serious and even tragic consequences Buffer Action 7.39 1.
Red, which is used to test for an alkali, if the substance is
alkaline the paper will turn blue. If the paper does not change color the substance is neutral (pH7). To indicate relative acid or alkali strength a universal indicator must be used. Universal indicators are available as paper strips or as solutions. The solutions will give a full spectrum of color changes, from red (acid) through to purple (alkaline). Each kit will contain a color matching chart which indicates the relative strength of the acid or alkaline condition. The pH Scale 7.41
Table 7.41A
A solution that rates zero on the above scale contains many hydrogen ions (H+) and few hydroxyl ions (OH-), whereas one that rates 14 has many hydroxyl ions and few hydrogen ions. A pH of 7 is neutral and contains one ten millionth (0.0000001) of a mole of hydrogen ions per litre. A solution that has more H+ ions than OH - ions, is acid and will be below pH7 on the scale. A movement of 1 whole number on the scale represents a 10 fold change on the previous condition. Strong acids and alkalis are corrosive and destructive of living tissue. Appropriate precautions should be taken when handling such substances. Chemical Analysis
7.42 Quantitative Chemistry 7.43 Quantitative measurements are of two types; 1. Volumetric measurements where the volume (usually gas or liquid) of the substance is expressed in litres or its sub-multiple the millilitre. 2. Gravimetric measurements that may apply to liquids or solids. A substance may be weighed, the unit of measurement is the kilogram or its sub-multiple, the gram. Alternatively we can determine the density of a substance in which case we refer to it as having mass per unit quantity, i.e. as grams per cubic centimeter ( g/cm� ). There is a third type of measurement that is concerned with the amount of matter in a substance, i.e., how many entities there are in a given quantity of any substance. The unit of measurement is the �mole�. Its symbol is �mol� and its mass per unit quantity is expressed as mol/L, or kg/mol. The Mole and Avogadro Constant,
7.44 One mole of any substance is its atomic mass number expressed in grams. This amount will contain as many �entities� as there are atoms in 0.012 kg (12 grams) of Carbon 12, which is the standard mole. It will be seen from the Periodic Table, that the elements do not have simple whole numbers, due to the presence of naturally occurring isotopes. It is sufficiently accurate to use the simple whole numbers rounded, e.g. Carbon12, Oxygen16, Nitrogen14 and so on. 12 g of Carbon 12, which is the standard mole, contains; 6.02252 x 1023 atoms. This number is called �Avogadro�s constant�, or Avogadro�s number. Therefore 1 mole of oxygen weighs 16g and contains ; 6.02252 x 1023 atoms. Avogadro�s number is astronomical, and when written in full it is quite incomprehensible. 602252 000 000 000 000 000 000. Avogadro�s number is often cited by orthodoxy to refute the homeopathic claim that the serial dilution of a remedy will increase its potency. According to Avogadro�s theory, when a serial dilution of 12c (centesimal) or 24x (decimal) has been attained, not a single molecule of the solute will remain in solution. Nonetheless, the enigma of homeopathy remains because undoubtedly high serial dilutions produce a very pronounced effect on a healthy person. Homeopathic pharmacy will be covered later in the text. Molar Solutions, 7.45 As stated, 1 mole of any substance is its atomic number expressed in grams, e.g. 1 mole of Hydrogen weighs 1 gram. And contains 6.02252 x 1023 atoms. 1 mol of Oxygen weighs 16 grams. In the case of a molecular compound, the atomic mass numbers are added together; for example water; its molecular formula is H2O and we wish to know the weight of 1 mol H2O, proceed as follows; Hydrogen atoms = 2 x 1 = 2g = 2 mol �H� 1 mol of any compound is its formula weight in grams. The concentration
of a solute in solution may be expressed in moles per litre (mol/L),
or as grams per litre (g/L). For example, a 1 mol per litre (1mol/L)
Saline solution, would contain 58g of Sodium chloride (NaCl) per
litre, e.g. Na = Sodium = 23g/mol
and Cl = Chlorine = 35g/mol. Total = 58g/mol which is expressed as 1 mole/L or 58g/L
NaCl. To calculate the density of a substance, the mass (weight) is divided by its volume. If the substance is a solid the answer will be expressed in grams per cubic centimeter (g/cm3). If the substance is a liquid, in grams per millilitre (g/ml). To calculate the density of a regular shaped solid, first weigh the sample, then calculate its volume. The weight is then divided by the volume. The formula is as follows; Density = Mass � Volume = g/cm� For example; a substance weighs 75 grams and its volume is 8.6 cm�, therefore, 75 � 86 = 0.872 g/cm� or s.g. 0.872 If the substance is a liquid, the calculation is the same, except the answer will be in grams per millilitre. If you refer to Table 6.31A it will show that the weigh per unit quantity, of a given substance (g/cm3) has the same numerical value as relative density or s.g. Accordingly, we may define s.g. as a ratio of the weight of a volume of a substance, compared to an equal volume of distilled water. Or in another way, the number of times that a substance is heavier or lighter that water;
Glycerin BP weighs 1.260 g/ml and its SG is 1.260 (at 20�) Temperature and Density
7.48 The density of a substance is a physical property which may be used for identification purposes with the proviso that the measurements, i.e., weight and volume are made at an agreed temperature and pressure. Standard temperature and pressure (STP) for chemical work is usually 0�C at 1 atmosphere. 0�C, the freezing point of water is not a convenient temperature for routine tasks, which are usually carried out at room temperature. In the older official publications this was defined as 60�F or 15.56�C, however since the introduction of the international SI units the agreed standard is 20�C (68�F). Metric measurements when given in a Pharmacopoeia are graduated at 20�C so there shall be no errors arising due to the expansion or contraction of solutions at other temperatures. This is particularly important when preparing hydro-alcoholic solvents which are specified for a particular substance. Considerable heat is evolved when the dilute alcohols are prepared, in addition there may be a disparity between room and solution temperatures. Accordingly, the SG of the alcohols will be shown at 20�/20�. That means the solution at 20�C and the ambient (surrounding) temperature at 20�. If measuring, by SG, a sample of alcohol and water at 20�C, we determine its alcoholic strength to be 14% by volume at 30�C. The same sample, due to expansion, would only contain 10.75% alcohol by volume. Alcometric and temperature correction tables will be supplied later in the text. Percentage Solutions 7.49 1. The percentage weight in weight is the only true percentage compound, and it means the weight of solute in a solution, or weight of active ingredient in the product, e.g. 4% w/w of Symphytum extract in an ointment or solutution. 2. The percentage as a volume in volume. This is not a true percentage compound due to the different density and weights of the constituents, e.g. a hydro-alcoholic solvent, Alcohol 30% v/v, which means 30 ml of alcohol in 100 ml of product. 3. The percentage as weight in volume. Again, not a true percentage compound, and it means the weight of active ingredient dissolved in 100 ml of product, e.g. Sodium Chloride 3% w/v. 4. The percentage, volume in weight, meaning the volume as mls of active ingredient in 100 g of product, e.g. Calendula tincture 7.5% v/w which is not a true percentage compound. Percentage Formulae 7.50 Occasionally formulae may be expressed as �parts�, for example; Alcohol - 3 Water - 7 This may mean: by volume, or by weight, in either case, the strength of the resulting solution would be different from each other, for example, Table 7.50A
Table 7.50B
Assuming that the alcohol is the active substance in the solution, then we may say that; 3 as a percentage of 7 is 3 �7 = 42.8% alcohol in the solution by volume. However, if we have compounded the solution by weight then the percentage of active substance is different, i.e. 3.69 � 7 = 52.7% alcohol. The difference is almost 10%, which is considerable. Another example would be that the formula may be a combination of liquids and solids as follows;
In all such formula the ingredients are weighed, with the exception of the water, because water weighs 1 gram per ml. The rectified formula would read as follows;
This is the method to be followed in the absence of specific instructions. As a further example the formula could be written as follows;
Water 90 ml. It will be understood that formulae �A� and �B� differ in quantities because of the relative density, or s.g. of the substances. If formulation �B� is intended, then it will be as such. Percentage Composition 7.51 Formulae may sometimes be given by weight and we may wish to prepare a differing quantity to that shown, accordingly, the active ingredient should be determined as a percentage of the total preparation, e.g. Acetic Acid 25 g Distilled Water 500 g In this instance, the acetic acid is the active ingredient and we proceed thus; 25 � 500 x 100 = 5% of the total As a further example, we may use the saline solution given in Section 7.45, i.e. 1 mole NaCl per litre = Common salt 58g. Distilled water 1000g. Therefore 58 � 1000 x 100 = 5.8% of the total. Proportions and ratio�s
7.52 Occasionally the formulae of medicinal substances are given in a variety of ways, e.g. common fractions or decimal fractions, and one must be able to manipulate the numbers to arrive at a desired term. The percentage represented by a ratio is arrived at in the following manner, e.g. 1 : 4 = 1 � 4 = 25%. Decimal Numbers and Fractions
7.53 Reading Decimal Numbers 7.54 Table 7.54A
Multiplying and Dividing Decimal Numbers 7.55 When multiplying a decimal number by units of 10, simply move the decimal point to the right by the number of zeros that there are in the multiplying number, e.g.
When dividing by units of 10, move the decimal point to the left by the number of zeros, e.g. 0.5 � 10 = 0.05 0.5 � 100 = 0.005 0.5 � 1000 = 0.0005 5% = 5/100 therefore 5 � 100 =0.05 20% = 20/100 � 20 � 100 = 0.20 43% = 43/100 � 43 � 100 = 0.43 Changing Decimal Fractions to Percentages
7.57 0.05 = 0.5% 0.20 = 20% 0.43 = 43% Changing Percentages to Common Fractions 7.58 Remember that percentage means the proportion, or rate per 100 parts, therefore, when converting a percentage to a common fraction, 100 is always the denominator, and the numerator is the percentage under consideration, for example 5%.
Denominator 100 parts The fraction is reduced to its lowest terms, that is when the only common factor between the numerator and denominator is 1, therefore, 5% is 1/20th of 100. Changing Percentage to Ratio
7.59 The ratio is then reduced to its lowest terms; Changing Ratios to Percent
7.60 1 : 4 = � x 100 = 25 then add the % sign i.e., 25%.
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