OPTICAL STUDIES OF PENICILLIN GROUP IN RELATION TO THEIR MEDICAL ACTIVITY

The study of Medical activity of antibiotics is gaining momentum now a days owing to the importance of their curative values. The Medical Activity correlated to molecular interactions, can be studied by various physical techniques, at present optical methods like Refractometry and Polarization are used to study the activity of a few antibiotics like Penicillin. The Refractive Indices Mean Molecular Polarizability Diamagnetic Susceptibilities and Electron Ionisation Cross Section are interpreted in terms of dosages and the toxic effects if any due to over dosages are discussed critically.


INTRODUCTION
Antibiotics are chemical substances excreted by some microorganisms, which inhibit the growth and development of other microbes.The study of the physical and optical properties of antibiotics plays a vital role in drug designing and understanding their pharmacological activities.Molecular biology & Biomolecular engineering are the two fields of research of much important in this direction.Though many physical techniques like UV, Visible, IR, NMR, Raman and Laser have been used to study the pharmacological activities in terms of chemical activities, but not much work has been done in utilizing optical Polarizabilities and related properties like Diamagnetic Susceptibilities, molecular ionisation cross-section as tools in this field.Rao et all [1] and Murthy et all [2,3] and Murthy and Jeevan Kumar [4] have been successfully used the techniques of the Polarizabilities in the confirmations of Biopolymers, synthetic polymers and Liquid crystals.This paper reports the study of Molecular Polarizabilities of few antibiotics (Penicillin Group), structures of these antibiotics are shown in the Fig. 1, by using Lippincot -function potential model, Molecular vibration method and through Bond Refractions and using the same to determine diamagnetic susceptibilities, electron ionisation cross-section and to correlate Q values with the degree of covalency on one hand and with the effective number of electrons on the other hand.And the results are discussed critically.

Mean molecular polarizabilities
Methods used to determine Mean Molecular Polarizabilities are 1.The method based on Lippincot -δ-function Potential Model [5].
The first two methods are based on Quantum Mechanical approach and Vibrational spectroscopic parameters respectively.
The last method is an empirical relation developed by Murthy et-al and it is based on the bond refractions.
Final expressions governing the above methods are given below.
α ||n -parallel components from the non bonded region electrons.

Molecular vibration method
Where b L and b T are the longitudinal and transverse Polarizabilities of i th and n i is the number of bonds of i th kind in molecule.

Method based on bond refractions
Where N is Avogadro's number ΣR ∞ is the summations of the bond refractions of various bonds present in the molecule.

Diamagnetic susceptibilities χM [8].
Diamagnetic susceptibilities and Mean molecular Polarizabilities depend upon the effective number of free electrons which will be free to take part in magnetic and optical interactions.In view of these considerations a semi empirical relation was proposed by Rao et-al [4], which is given as γ = (0.9) n represents saturation state of the molecule with n denoting the number of unsaturation rings and bonds present in the molecule.
σ 1 is the degree of the covalency of the characteristic group.And m = 0.72  10 19 is characteristic constant.The diamagnetic susceptibility values of Penicillin group compounds are determined here by substituting α M values calculated by various methods in the above expression.

Molecular electron ionization cross-section [9]
The molecular electron ionization (Q) of the various antibiotics is calculated utilizing diamagnetic susceptibilities using Rao and Murthy's relation.
The mean molecular polarizabilities, diamagnetic susceptibilities and molecular electron ionization cross sections of various antibiotics such as few compounds of penicillin group are determined by the above methods and are listed in the tables 1, 2, 3 & 4, respectively.

RESULTS AND DISCUSSIONS
From table 1 it is seen that the agreement among mean molecular polarizability values obtained by Lippincot -δ-function method, Molecular Vibration method, Bond refractions and Addition bond Polarizabilities are very good.Since the experimental values of α M for these compounds are not available, it is not possible at present to compare these values with the experimental values.Since bond Polarizabilities are accepted as one of the standard method to evaluate α M by Le Fevre [10], the values obtained by this method may be taken as reference datum for comparison.However, the good agreement among the results reveals, beyond doubt, their reliability as well as the applicability of these theoretical methods for the evaluation of mean molecular Polarizabilities of antibiotics.
A glance at the tables 2 & 3 reveals the good agreement among the values of χ M and Q values obtained by using α M (from Lippincot -δ-function method, Molecular vibration method and Additions bond Polarizabilities), values.However the comparison of χ M and Q is also not possible as they are not reported so for.But Subbaiah [9] applies these methods for many systems and theoretically computed values were reported to have good agreement with the experimental values.Hence χ M and Q values calculated for these antibiotics are taken to be fairly reliable.
In the case of molecular ionization cross-section, the concept of Qeffective is used.The substances which are added to the main group are treated as separate group, then the activity of the entire antibiotics can be explained in terms of the activity of the main group + that of the substituents.For example in cyclic compounds, the effective Q can be fit with the calculated Q by the following relationship.
Where p i refers to the effective number of electrons of substituent group i and α is constant and is equal to 1  10 -16 the Q effective values of these antibiotics are listed in table 4 and they are also in good agreement with the computed Q values.
A graph is drawn between Q 1/2 and σ 1/2 [Fig.2].This shows a regular variation there by showing that the ionization activity and degree of covalency are well related through the number of free electrons (available for reaction) present in the antibiotics [11].Thus the electron ionization cross section could be correlated to the degree of covalency on one hand and with the effective number of electrons on the other hand.The larger the values of Q, the higher the efficiency of the molecule to partake in the reaction.This is also reflected in increase in value of σ, the degree of covalency.We could thus see that σ 1/2 is proportional to Q 1/2 , with a maximum deviation being about 8%.Efforts to quantify the relation between Q and the reactivity of the antibiotics are in progress.
Fig. 2: Relation of Q with .

Fig. 1 :
Fig. 1: Some Natural and semi synthetic pencillins showing the basic core of 6-aminopenicillanic acid with side chains which differ, thereby conferring special properties.

Table 4 :
The relation of Q with σ.