I. Enzymatic activity of saliva. II. Synthesis and characterization of some amine derivatives of 2-chloro-1,4-naphtho quinone

120 Pages·06.917 MB·English

by  Adams, Ernest Clarence, Jr

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I. ENZYMATIC ACTIVITY OE SALIVA
SYNTHESIS AND CHARACTERIZATION OE SOME AMINE
DERIVATIVES OE 2-CHL0R0-1,4-NAPHTHO QUINONE
A DISSERTATION
SUBMITTED TO THE GRADUATE SCHOOL
IN PARTIAL EULEILLMENT OE THE REQUIREMENTS
for the degree
DOCTOR OE PHILOSOPHY
DEPARTMENT OE CHEMISTRY
by
Ernest Clarence Adams, Jr.
Evanston, Illinois
August 1950
ProQuest Number: 10060807
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ACKNOWLEDGMENT
Tli© author wishes to express his appreciation to Dr,
J. C. Calandra for his encouragement and guidance throughout
the course of these investigations. Thanks are also due to
Miss leannette Mier for carrying out the studies of the
inhibition of acid formation in saliva and for some of the
nitrogen analysis; to Parke, Davis and Co* for the results
against Entameba histolytica.
TABLE OB CONTENTS
Part I. ENZYMATIC ACTIVITY OE SALIVA
Introduction................................ 1
Eactors involved in dental caries .................. 2
Role of ammonia as a possible factor in caries* . . .
immunity.............................. . . o ♦ « • 4
Sources of salivary ammonia ......................... 6
Review of the literature on amino acid oxidases . . • 8
Oxidation of glucose degradation products as a
possible factor in caries immunity................14
Review of literature on oxidation of small molecular
weight acids by enzyme systems......................14
Review of literature on fatty acid oxidases............16
Statement of Problem . . . . . . . . . . . . 18
Experimental................................... 19
Principle of the Warburg Respirometer .............. 19
Calculation of flask constants................... 20
Calibration of flasks and manometers . . 23
Reading of the Warburg Manometer....................25
Temperature control .................................. 27
Use of L- and D- amino acid oxidase inhibitors. . . . 28
Experimental procedure............... ...............32
Method for expressing the data.................... .. 34
Results. . . o • • . ............* * ................ . 36
Graphs.......................................... 36-62
Table of Activities............................. 63
Discussion ....................................... 64
Comparisons of rates of oxidations of the amino acids 64
Controlling factors in the rate of ammonia production 66
Possible importance of the oxidation of lactate,
pyruvate, acetate, and propionate to caries
immunity. ............... . . . . . . . . . 70
Sources of the enzymes. ................... 75
Conclusions. .............. . . . . . . 76
Summary. . . . <, . . 76
Bibliography . . 78
Part II. SYNTHESIS AND CHARACTERIZATION OF SOME AMINE
DERIVATIVES OF 2-CHLQR0-1,4-NAPHTHO QUINONE. . . . . . 82
Introduction ........................................... 83
Review of the Literature on antibacterial action of
naphthoquinones..................................... 84
Review of the literature on the synthesis of
naphthoquinone derivatives........................... 88
Statement of Problem................ 89
Experimental.......................................... 90
Synthesis .................................. 90
Sulfapyridine derivative.............. * ............ 91
Sulfathiazole derivative. . . . . • • . * • • • • « 91
Sulfadiazine derivative ........................... 91
Sulfamerizine derivative. .................. 92
Sulfaguanidine derivative............ . ............ 93
2-Amino-5-methylpyridine derivative . . ............ 93
2-Amino-4-methylpyridine derivative . . . . . . . . 93
2-Amino-6-methyIpyridine derivative.................93
n-Decylamine derivative ................ . . . . . 94
£T-Aminocaproic acid derivative.......... . . . . . 94
Guanidine carbonate derivative.......................94
Morpholine derivative . . . . ..................... 95
6-Hydroxyethylamine derivative.......................95
Preparation of alkali metal salts.....................95
Inhibition of acid formation determinations . . . . . 96
Discussion of possible structures. . . . . .. ........... 97
Results............................................... .9 99
Inhibition of acid formation - Table 1.................99
In vitro amebicidal tests...................... . . 102
Discussion.......................... 103
Mechanism of action........................ 105
Summary. .......... 110
Bibliography.............................. Ill
Vita ...............................................112
PART I
ENZYMATIC ACTIVITY OP SALIVA
1
The etiology of dental caries lias been obscure until
the past few decades. It is now agreed by most authorities
that the formation of dental caries is due to the decalci­
fication of enamel by acids formed by the degradation of
carbohydrates. This theory has been objected to on the
grounds that the incidence of dental caries is often not a
function of the carbohydrate intake, because individuals
with the same hereditary background and with similar diets
have different caries rates and therefore other variables
are concerned. The research on this question has been direc-
jted along two lines: (1) To find and correlate these vari-
jables; (S) To find inhibitors for the degradation reactions.
i
|It is hoped that this paper will draw these two lines of
ji investigation closer together.
S First, it is desirable to examine the possible faetors
i>
|influencing dental caries. These factors may be grouped
;under two headings: The rate of acid formation in the mouth;
|and the rate of acid destruction or neutralization in the
mouth. The factors under the two headings are listed in
ijthe following outline:1
ji
■i
l|
'il. Fosdick, L.S. "Dental Caries". Pamphlet, Chemistry
' Department, Northwestern University Dental School,
Chicago, Illinois.
2
Rate of Acid Formation
A. Substrate
1. Starch
2* Fermentable sugars
B. Enzyme Systems
1. Bacterial flora
2. Tissue enzymes
3. Coenzymes
Rate of Acid Destruction
A. Rate of Acid Neutralization
1. Buffering Capacity
a. Diet alkalinity
2. Flow of Saliva
3. Calcium and Phosphorus Content
B. Other Pathways of Degradation
1. Oxidation of pyruvic and lactic acids
C. Physical Features
1. Anatomical
a. Diet and nutrition during formation
b. Pits, fissures, occlusions
2. Mechanical
a. Heredity
b. Diet
c. Oral hygiene