REDEFINING HOMEOPATHY

Chandran K C Explains Homeopathy As Molecular Imprints Therapeutics (MIT)

Target-Specific Drug Designing By ‘Molecular Imprinting in Water’ Can Revolutionize Pharmaceutical Industry


 ‘Drug designing’ is an advanced branch of modern pharmaceutical chemistry, which is involved with the process of developing new medicinal substances appropriate to the specific  biological targets in the organism. Such a ‘designer drug’ is most commonly a small organic molecule which can inhibit or activate the functioning of a target biomolecule such as a protein, thereby resulting in a therapeutic process in the organism. Essentially, ‘drug designing’ involves the development of small molecules that are complementary in ‘shape’ and ‘charge’ to the biomolecular target to which they interact and therefore will bind to it. Modern drug designing protocols utilize computer modeling techniques also. This type of modeling is known as ‘computer-aided drug design’. Actually, ‘drug design’ is involved with ‘ligand’ design. Prediction of binding affinity of molecules to be designed is the first step in a successful modeling technique.  Many other properties such as bioavailability, metabolic half life, lack of side effects, also should be optimized before a designed ‘ligand’ can become a safe and efficacious drug. Most of these ‘other’ characteristics are often very difficult to optimize using presently available drug design techniques.

Selection of drug target is most important in “drug designing”. A drug target is typically a key molecule involved in a particular metabolic or signaling pathway that is specific to a disease condition or pathology, or to the infectivity or survival of a microbial pathogen. Most of the therapeutic inteventions aim to inhibit the functioning of the ‘pathologic’ pathway in the diseased state by causing a key molecule to stop functioning. Drug molecules may be designed that bind to the active region and inhibit this key molecule. Some other therapeutic interventions  actually enhance the ‘normal’ biochemical pathway by promoting specific molecules in the ‘normal’ pathways that may have been affected in the diseased state. Main challenge in all ‘drug therapies’ including ‘designer drugs’ is that  these drug molecules should not affect any other important “off-target” molecules or ‘antitargets’ that may be similar in appearance to the target molecule, since drug interactions with off-target molecules may lead to undesirable side effects.

Designer drugs are small organic molecules produced through chemical synthesis, but biopolymer-based drugs (also known as biologics) produced through biological processes are becoming increasingly more common in modern drug designing.

‘Ligand-based drug design’ and ‘structure-based drug design’ are two major technologies now utilized in drug designing technologies.

Ligand-based drug design is based on the knowledge of other molecules that can bind to the biological target of interest. These other molecules may be used to derive a ‘pharmacophore’ which defines the minimum necessary structural characteristics a molecule must possess in order to bind to the target. In other words, a model of the biological target may be built based on the knowledge of what binds to it and this model in turn may be used to design new molecular entities that interact with the target.

Structure-based drug design is based on the knowledge of the three dimensional structure of the biological target obtained through methods such as x-ray crystallography or NMR spectroscopy. Using the structure of the biological target, candidate drugs that are predicted to bind with high affinity and selectivity to the target may be designed using interactive graphics.

Main draw back of ‘designer drugs’ is that  there is a chance for these drug molecules affecting “off-target” molecules or ‘antitargets’ having similarity to the target molecules. Such interactions with off-target molecules may lead to grave consequences. Optimizing of various factors such as bioavailability, metabolic half life, and lack of side effects are the real challenges facing “drug designing” technology.

Molecular Imprinting in Polymers:

  ‘Molecular imprinting in polymers’ is a fast grownig research area that may be interesting to people engaged in developing “drug designing” techniques. A lot of research is currently going on over this subject the world over. This technology involves the imprinting of synthetic polymer substances using enzymes or such macromolecules as ‘guest’molecules. As a result of imprinting, nano cavities with 3-d spacial configurations complementary to the ‘guest’ molecules will be created in the interaction surfaces of the polymers. These imprinted polymers, by virtue of the nanocavities they contain can be used to bind molecules with configurational similarity to ‘guest’ molecules. They are at present widely used in various laboratory assays as powerful adsorption surfaces. MIPs are also found to be of much practical use in various areas of science  and technology .

Molecular imprinted polymers of today cannot be used as therapeutic agents, since they are totally foreign substances to the organism. More over, native enzymes can not degrade the polymers even if they can play a therapeutic role in the organism.

Molecular imprinting may become part of future drug designing techniques, only if the search for safer substances and methods for molecular imprinting happens to be successful.

Molecular Imprinted Proteins:

 Biopolymer-based drugs (also known as biologics) produced through biological processes are becoming increasingly more common in modern drug designing. But the revolutionary concept of molecular imprinting in proteins is only in its emerging stage, which may have implications in drug designing techniques. It has already been acknowledged that the biological molecules presently classified as antibodies are nothing but native globulin proteins subjected to natural molecular imprinting process with foreign pathologic proteins acting as ‘guest’ molecules. Scientists have already realized the fact that the much discussed pathologic molecules known as ‘prions’ are nothing but disfigured protein molecules subjected to molecular imprinting. Protiens, being polymers with complex and flexible tertiary structures,  are expected to be a very good medium for molecular imprinting. Different types of protein based substances, subjected to artificial molecular imprinting, may  evolve in the future as effective therapeutic agents and laboratory reagents.

Apart from protein molecules,  different types of biopolymers such as polysaccharides and nucleic acids also may be experimented as medium for molecular imprinting.

Native proteins extracted from the patients could be subjected to molecular imprinting with appropriate ligands or other pathologic molecules acting as ‘guest’ molecules and used as target oriented therapeutic agents.  But the problem remains that such imprinted proteins can be used only in the individual whose proteins are used for imprinting. Otherwise it may result in grave anaphylactic reactions. Moreover these imprinted proteins may remain in the organism for very long periods, without undergoing degradation, and cause ever new pathological molecular blocks. Such issues have to be addressed properly.

Molecular Imprinting in Water:

 Our protracted search for a safe and reliable universal medium for molecular imprinted drug designing finally takes us to the study of wonderful physico-chemical properties of the most abundant substance on earth called water. But the concept and technology of molecular imprinting in water still remains in very infantile stage. The author is of the opinion that with its strange polymer-like behaviours, capable of forming hydrogen-bonded supra-molecular structures, water can be the ideal candidate for molecular imprinted drug designing in future.

Though in a slighly lesser level, Ethyl Alcohol and Lactose are also capable of forming polymer-like supra-molecular formations through hydrogen bonding, and hence may be onsidered as  candidates for molecular imprinting experiments. Possibilities of these substances in combination with water also have to be explored.

Water(H2O) is a wonderful substance with strange physico–chemical properties arising from its peculiar supra-molecular structure. Water is a solvent with higher polarity than similar liquids. H–O–H bond angle is 105 degrees. That means, water molecule is a dipole. Because of this peculiarity, water molecules can exist like a supra-molecular network through hydrogen bonding.  A minimum number of five water molecules will be contained in this network. Such supra-molecular formations are called pentamers. Most of the wonderful properties of water arise from this peculiar capacity of hydrogen bonding and resultant supra-molecular formations. Water molecules (H2O) are symmetric (point group C2ν) with two mirror planes of symmetry and a 2-fold rotation axis. The hydrogen atoms may possess parallel or antiparallel nuclear spin. The water molecule consists of two light atoms (H) and a relatively heavy atom (O). The approximately 16-fold difference in mass gives rise to its ease of rotation and the significant relative movements of the hydrogen nuclei, which are in constant and significant relative movement.

Although not often perceived as such, water is a very reactive molecule available at a high concentration. This reactivity, however, is greatly moderated at ambient temperatures due to the extensive hydrogen bonding. Each water molecules possess a strongly nucleophilic oxygen atom that enables many of life‘s reactions, as well as ionizing to produce reactive hydrogen and hydroxide ions. Reduction of the hydrogen bonding at high temperatures or due to electromagnetic fields results in greater reactivity of the water molecules.

As liquid water is so common-place in our everyday lives, it is often regarded as a ‘typical’ liquid. In reality, water is most atypical as a liquid, behaving as a quite different material at low temperatures to that when it is hot. It has often been stated that life depends on these anomalous properties of water. In particular, the high cohesion between molecules gives it a high freezing and melting point, such that we and our planet are bathed in liquid water. The large heat capacity, high thermal conductivity and high water content in organisms contribute to thermal regulation and prevent local temperature fluctuations, thus allowing us to more easily control our body temperature. The high latent heat of evaporation gives resistance to dehydration and considerable evaporative cooling. Water is an excellent solvent due to its polarity, high dielectric constant and small size, particularly for polar and ionic compounds and salts. It has unique hydration properties towards biological macromolecules (particularly proteins and nucleic acids) that determine their three-dimensional structures, and hence their functions, in solution. Hydration of biological molecules results in formation of gels that can reversibly undergo the gel-sol phase transitions that underlie many cellular mechanisms. Water ionize and allows easy proton exchange between molecules, thus contributing to the richness of the ionic interactions in living organisms.

In reality, hydrogen bonding is a special type of dipole force. It is a force of attraction formed between partial electro negative atom which is part of another molecule. The reason for strength is the partial positive charge attained by hydrogen. Hydrogen is capable of establishing similar bonds with the atoms of nitrogen, fluorine and oxygen. That is to say that the basis of hydrogen bonding is the attraction between one hydrogen atom which is part of a molecule which is attached to oxygen or nitrogen and  oxygen or nitrogen which remains part of another molecule. This force is less powerful than the co–valent bonds which keeps the atoms inside molecule bound together. But these less powerful bonds are responsible for the wonderful bio–chemical qualities of water.

In the ordinary liquid state, in spite of 80% of the electrons being concerned with bonding, the three atoms in water do not stay together, as the hydrogen atoms are constantly exchanging between water molecules due to protonation/deprotonation processes. Both acids and bases catalyze this exchange and even when at its slowest (at pH 7), the average time for the atoms in an H2O molecule to stay together is only about a millisecond. As this brief period is, however, much longer than the timescales encountered during investigations into water’s hydrogen bonding or hydration properties, water is usually treated as a permanent structure.

Water molecules are normally considered to be in a state of random movement in their liquid form. But recent studies have shown that water molecules move not as individual molecules, but as supramolecular clusters. We all know that water exists as ice crystals in its solid form. But it has been recently observed that in its short range structure, water exist as nanocrystals  even in its liquid form.

The presence of ethyl alcohol in water is considered to be a factor reducing the rate of protonation/deprotonation processes, thereby enhancing the stability of hydration shells.

Hydrogen bond strength can be affected by electromagnetic and magnetic effects.

Any factors, such as polarization, that reduces the hydrogen bond length, is expected to increase its covalency. There is still some dispute over the size of this covalency, however any covalency will increase the network stability relative to purely electrostatic effects. As hydrogen bond strength depends almost linearly on its length (shorter length giving stronger hydrogen bonding), it also depends almost linearly (outside extreme values) on the temperature and pressure .

Hydrogen bonded chains (that is, O-H····O-H····O) are cooperative; the breakage of the first bond is the hardest, then the next one is weakened, and so on. Thus unzipping may occur with complex macromolecules held together by hydrogen bonding, for example, nucleic acids. Such cooperativity is a fundamental property of liquid water where hydrogen bonds are up to 250% stronger than the single hydrogen bond in the dimer. A strong base at the end of a chain may strengthen the bonding further.

Water-Ethyl Alcohol Mixture :

 At this stage we have to understand a few facts about Ethyl Alcohol(CH3- CH2 – OH ). The molecules of alcohol also have the dipole structure as water molecules. It is possible for them to establish mutual connection through hydrogen bonding. The molecular weight of alcohol molecul is 46. The molecular weight of water(H2O) is 18. That means that the number of water molecules contained in 18 gram of water and the number of alcohol molecules contained in 46 gram of ethyl alcohol are equal. When alcohol and water are thoroughly mixed alcohol molecules network with water molecules through hydration bonds, The mobility of water molecules is restricted by the bonds established with alcohol molecules. Hence, hydration shells formed in alcohol–water mixture are comparatively more stable. The count of alcohol molecules and the count of water molecules contained in their mixture in 73:27 ratio will be equal. (73% w/w. alcohol and 27% w/w water) This mixturei is known as (40 power   spirit).

Ideal medium for molecular imprining is supposed to contains 87% w/w of alcohol and 13% w/w of water. In this ratio, the number of alcohol molecules will be about more than that of of water molecules. Such a ratio will be very suitable for the production of stable hydration shells. More over, the presence of ethyl alcohol in water is considered as a factor reducing the rate of protonation/deprotonation processes, thereby enhancing the stability of hydration shells

Water/Ethyl alcohol mixture in RECTIFIED SPIRIT ratio is an AZEOTROPIC MIXTURE. in An azeotrope is a mixture of two or more liquids in such a way that its components cannot be altered by simple distillation or evaporation. This happens because, when an azeotrope is boiled, the vapor has the same proportions of constituents as the unboiled mixture.  In AZEOTROPIC MIXTURES, hydrogen bonds are highly stable

We know that water is a good solvent. Let us see what happens when some foreign molecules are made to dissolve in water. If a foreign(called ‘guest’) molecule, ion,  or colloidal particle happens to enter the matrix of 3-dimensional dynamic network of water molecules, they are entrapped inside this network. Water molecules arrange themselves around the ‘guest’ molecule in a peculiar way by the formation of hydrogen bonding. These formations of water molecules around the ‘guest’ molecules is known as hydration shells. These hydration shells exist in a dynamic state, and are more or less unstable. The ‘guest’ molecules dissolved in water exist in a state of being entrapped inside these hydration shells. This phenomenon can be seen both in ionic solutions and colloidal solutions. Obviously, hydration shells assume an internal spacial arrangement exactly fitting to the 3-dimensional spacial configuration of the ‘guest’ molecule entrapped in them. If we could devise some technique to remove the entrapped ‘guest’ molecules from these hydration shells, without disturbing the hydrogen bonds between the constituent water molecules, these hydration shells can retain the molecular memory of the molecular configurations of the removed ‘guest’ molecules. This rarely studied phenomenon underlies the much debated controversial ‘molecular memory of water’. Actual mechanism and forces underlying this phenomenon have to be investigated minutely by physical scientists. Minute changes occuring in the electron clouds of atoms of water molecules during the formation of hydration shells may be one factor responsible for this phenomenon. It has been well proven that these hydration shells later show a peculiar capability to differentially recognize the original ‘guest’ molecules which were  responsible for their formation. This may be due to the existence of some imprinted memory of those host molecules retained in the hydration shells. This imprinting of memory may be compared to formation of finger prints. As in the case of finger prints, configuration of these molecular imprints also will be a complementary negative of ‘guest’  molecules.  These empty hydration shells, or supra-molecular formations of water subjected to molecular imprinting, may be called ‘hydrosomes’, which means, minute ‘cavities of water’.

Homeopathic process of potentization may be a crude method of preparing hydrosomes, imprinted with various drug molecules(‘guest’), for utilizing as therapeutic agents.  It should be specially noted that the medium used for homeopathic potentisation is not pure water, but it is mixed with ethyl alcohol in a particular ratio. It may be  inferred that the presence of camparatively heavy ethyl alcohol molecules in this mixture may be contributing to stabilize the hydrosomes, preventing their easy dissociation.  The convergent forces of rotational movements to which the mixture is subjected as part of homeopathic potentization, may also be a contributing factor in stabilizing the empty hydration shells.

This peculiar 3-d configuration of ‘hydrosomes’ are destroyed only when the energy level of water molecules are disturbed by the effect of heat,  electricity, magnetism and other electro magnetic radiations. As stated earlier the hydration shells formed in pure water are comparatively unstable. Here lies the importance of the fact that homeopathic potencies are made using alcohol- water mixture.

Information we recently receive from various research institutions, regarding the wonderful  supra-molecular structures of various materials and their hitherto unknown peculiar properties, may greatly contribute in our  efforts to devise a protocol for molecular imprinted drug designing using water. Studies on  ‘water clusters’, ‘crystalline structure of water’, ‘shape memory property’, ‘molecular imprinting’,  ‘nano technology’,  ‘clathrate formations’ and other diverse phenomena are offering promising indications in this direction. We have to utilize all these new revealations in our scientific study regarding the possibility of developing a technology of drug designing by molecular imprinting in water.

We all know that water exists as ice crystals in its solid form. But it has been recently observed that water can exist even in its liquid form in crystals. In reality, water formed by melting of ice is in a state of liquid crystals. The lattice structure which is formed through hydration bonds is responsible for this phenomenon. Molecular imprinting in water is much interested in this area of research pertaining to this peculiar crystalline nature of water. It is believed that in the process of molecular imprinting of water using ‘guest’ molecules,  this crystalline structure of water plays a crucial role. It is likely that more advanced studies about dynamics of crystallization of water may help us to evolve a perfect technology for molecular imprinting in water.

The studies about Clathrate Compounds or host-guest compounds in supra-molecular chemistry is an area in which we should have sincere interest. Clathrates are the molecular networks which are formed when gases dissolve  in water under high pressure. They exist in a peculiar host–guest relationship. The studies about this phenomenon are still in their infancy. Clathrates have a crystalline nature,  existing as molecular networks,  formed by a process of water molecules arranging around the guest molecules. The studies about the dynamics of clathrate formation are also likely to help in evolving a perfect protocol for molecular imprinting in water. Even if  the host molecules are removed from clathrates, the network of water molecules have been found to remain intact. More over, the existing clathrates can induce the formation of similar clathrates.It will be very useful to consider these above discoveries connecting them with the phenomenon of molecular imprinting.

A lot of studies has been so far published regarding shape memory materials.  Several alloys having  crystalline structure have been observed to possess shape memory property. Such materials are known as SMART materials. This phenomenon also has to be understood well while trying to evolve a molecular imprinting technique of drug designing.

It is in the phenomenon of ‘molecular memory of water’ itself that we naturally land on when we attempt to develop molecular imprinted drugs. We have already seen that the alcohol–water molecules contained in the medium used for imprinting  arrange themselves around the ‘guest’ molecules, and form hydration shells. We should develop a way to systematically remove the ‘guest’  molecules entrapped in the hydration shells, so that empty hydration shells or ‘hydrosomes’ remain. These ‘hydrosomes’ will be imprinted with the three-dimensional ‘finger print’ of ‘guest’ molecules used for imprinting.

When molecular imprinted water is  introduced into the organism by any route, is carried by the body fluids, and transported to different parts of body. When molecular imprints come in the vicinity of ligands or active groups of pathological foreign molecules having similarity to the original ‘guest’ molecules, these molecular imprints selectively bind to those pathological molecules. By this process, pathological foreign molecules are prevented from binding with biological molecules, thereby relieving the biological molecules from pathological molecular blocks. This can be described as some sort of ‘molecular scavenging’ or entrapping of pathological molecules, by ‘hydrosomes’ or “molecular imrints”.

Drugs designed through molecular imprinting in water will be the safest of all therapeutic agents so far used in the history medical science. Though there is a chance for these molecular imprints affecting “off-target” molecules or ‘antitargets’ having similarity to the target molecules, such interactions will be of very transient nature, since these molecular imprints will be easily degraded into constituent water-ethyl alcohol molecules. Such temporary interactions with off-target molecules may not lead to any dangerous consequences. Factors such as bioavailability, metabolic half life, and lack of side effects also will be obviously remain in favorable range.

Using various ligands and pathological molecules involved in each disease process as ‘guest’  molecules, we can develop most appropriate specifc designer drugs against almost any disease. Instead of original pathological molecules or ligands, drug molecules having configurational similarity to them also can be used as “guest” molecules in the molecular imprinting protocol. Homeopathic potentization utilizes this strategy, which is the real essence of “similia similibus curentur”. I  hereby appeal to the government and scientific community to take up this task with urgent priority, so that a whole new range of safe and effective designer drugs could be developed though this novel process of molecular imprinting in water.

Read also: https://dialecticalohmeopathy.wordpress.com/2012/08/30/homeopathic-potentization/

3 Comments

  1. Hi it is a really innovational study towards the Molecular Imprinting.This helps to deeply study & theorize the mechanism of Homoeopathy before the world in a more scientific way…….

    Like

    • Chandran K C

      Thanks for your nice comments

      Like

  2. A learned and deep study of molecular imprinting. A study that opens our minds to future drug imprinting possibilities, of clathrates, and hydrosomes.

    Like

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