Hydrogen bonding abilities of hydroxamic acid and its isosteres

This book comprises seven chapters. In chapter 1 an overview of chemistry, biological functions and literature studies of hydroxamic acids (HA) and its isosteres is presented. The principles of quantum mechanics underlying the computational methods employed to study HAs are given in brief. Chapter 2 describes intra- and intermolecular H-bonding interactions between formohydoxamic acid (FHA) and single water molecule and the dimerization among the isomeric forms. Chapter 3 involves the comparative study of H-bonding abilities of thioformohydoxamic acid (TFHA) and FHA. The deprotonation enthalpies of different sites of FHA and TFHA, probable pathways for interconversion among anions and their H-bonding with water are explored in chapter 4. The Effect of aqueous medium on deprotonation by using solvation methods is also discussed. Further insight into H-bonded aggregates and dimers of HAs is gained through the analysis of calculated stabilization energies and their comparison to similar H-bonded functionalities. The reasons behind the H-bond cooperativity in the aggregates and dimers are explored in chapter 5. Chapter 6 deals with the study of properties of formylphosphinous acid (FPA) isostere of FHA and a comparative study is carried out. In chapter 7, the aggregation of the most stable keto and enol conformer of FHA and TFHA with five amino acid side chain groups occurring at active sites of enzymes is studied.

Autorentext

i passed MSc. Chemistry (gold medalist) in 2003 from GNDU, Amritsar, Punjab, India and obtained doctoral degree under guidance of Dr. Damanjit Kaur also from same university in 2012. The broad area of research was theoretical (physical ) chemistry. The topic of research was study of hydroxy amides particularly hydroxamic acids, exploring its various properties like tautomerism, proton affinities, deprotonation affiniities, solvent effects, substituent effects, hydrogen bonding studies with water and with amino acid side chain model molecules etc. I am in teaching profession for 7 years and presently serving as Asstt. Prof. at a reputed college. i have got nine research papers published in international journals with good impact factors.

Leseprobe
Text sample:
Chapter 3: INTRA- AND INTERMOLECULAR HYDROGEN BONDING IN THIOFORMOHYDROXAMIC ACID:
3.1 INTRODUCTION:
The nature of hydrogen bonds (H-bonds) formed by sulfur is quite different from that formed by oxygen atom and is known further from much familiar examples of H2O and H2S. According to electrostatics, sulfur atoms are usually positive and oxygen is negative, so the fundamental nature of H-bonds is anticipated to be different in them [1]. Though the electronegativity difference between H and S is just 0.38 on the Pauling scale, yet there are reports that the H-bond acceptor ability of thioamide sulfur could surprisingly be equal to or exceed that of amide oxygen [2-4]. There is scarce information available on H-bonding involving sulfur atoms.
The living systems contain a number of sulfur containing molecules including thiopeptides, amino acids e.g. cysteine and methionine etc. Hence understanding biomolecular interactions during protein folding by studying S...H bonding carries prime importance in biochemical research [5]. N-H...S H-bonds are suggested to be present at the active site of various cytochrome P450s and these H-bonds play crucial role in stabilizing the Fe (III) state and protecting the complex against decomposition [6,7]. The influence of N-H...S interactions in regulation of redox potential of the metal-sulfur proteins and other complexes is well known [8,9]. Since the fundamental building block in thiopurines and thiopyrimidines is S=C-NH- and these are H-bonded in the nucleic acids (DANN and RNA), thus thioformohydroxamic acid (TFHA) can serve as a model for studying H-bonds in these systems [10].
The presence of N-methylthioformohydroxamic acid has been recognised in bacterial sources and is commonly termed Thioformin [11]. The antibiotic activity of cupric and ferric complexes of N-methylthioformohydroxamic acid is also reported [12,13]. Thiohydroxamic acids are important in biological and analytical chemistry and are utilized in detection and quantitative determination of metals [14]. Using 'S' and 'O' atoms thiohydroxamic acids coordinate with metal ions like Fe+3, Ni+2, Cu+2 forming colored metal complexes and hence find applications in detection and quantitative estimation of metals [15,16]. A number of thiohydroxamic acids found applications as biocidal compounds for bacteria, fungi, insects, mites and weeds etc. They are effective as antiperspirant and antihypertensive agents, as enzyme inhibitors, and as drugs for treatment of leukaemia. Thiohydroxamic acids have also been used to counteract the effect of war toxins and to alleviate paralysis [17]. Their other important applications include gravimetric and spectrophotometric determination of metals. Cyclic thiohydroxamic acids such as 1-hydroxy-2(1H)-pyridinethione and 3-hydroxy-4-methyl-2(3H)-thiazolethione find diverse applications as fungicides and alkoxy-radical precursors in synthetic procedures and mechanistic studies [18]. It is used in personal care formulation such as hand lotions, emollient creams or in shampoos etc. Zinc chloride, acetate or oxide complex of this compound gives enhanced microbiological activity [19].
Inspite of numerous applications of thiohydroxamic acid, very few studies have been carried out to understand the chemistry of these molecules. Formohydroxamic acid (FHA) has undergone structural analysis by a number of research groups due to ist vast number of applications [20,21]. The intra and intermolecular H-bonding ability of FHA has already been analyzed by us (previous chapter) and reported [22]. Thiohydroxamic acid is expected to undergo tautomerism as observed in FHA. The earlier experimental reports based on IR spectral studies suggested that thiohydroxamic acid exists in thione form in solid state [23,24]. However the natural products separated from plants (e.g. mustard) contain sulfated S-glucosyl thiohydroxamates that are derivatives of thiol form [17]. The intra and intermolecular H-bonding inter