Krafft SpiralMolecularStructures TheBasisOfLife 2nd.ed

7/28/2019 Krafft SpiralMolecularStructures TheBasisOfLife 2nd.ed

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Spiral Molecular Structuresthe Basis of Life.

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SPIRAL MOLECULAR STRUCTURESTHE BACIS or LIFE.(Second Edition)

- -D- r=\

oyC^.rl F. Krafft,

Washington., D. C.

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1.

SPIRAL MOLECULAR STRUCTURESTHE BASIS OE LIFE.Introduction.

Thoro arc certain iDiological proc3GSGS suchas growth, va,riation, and reproduction, which areexhibited by 3V :ry living organism, regardless ofits rank in the plant or animal kingdom. Theseprocesses establish in nature a sharp line ofdemarcation between living and ncn-living things,since none of the phenomena of physics or chemistryexhibit anything that is similar or analogous tothese fundamental life processes.Biological grov;th involves not only theaccretion of tissue-building material, but alsomany remarkable chemical transformations whichtake place during metabolism, as well as thedev elopmierit, in m.ost cases, of highly complex andheterogeneous structures. The nearest approach tothis in the inorganic world is the growth of crystals,

but crystal growth produces neither the remarkablechemical transformations nor the complex structureswhich often result from biological growth, not tomention several minor differences such as thepolyhedral form of crystals as distinguished fromthe rounded form of most living organisms, andthe hardness of crystals as distinguished from thesoftness of most living tissues. The differencesbetv^een crystal growth and biological growth areso manifest that it seems hardly fair to assignthem to the sam.e category, and much less to pro-pose the one as an explanation for the other.

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2.

Biological variation differs from all inor-ganic changes and motamorphosos in that the newlyacquired structuroc cxort a directing influenceupon the future grov/th of the individual, and areperpetuated "by a process of heredity.Biological reproduction is like-zrisG so dis-similar from any of the other processes of naturethat it seems impossible to establish even theremotest analogy, and much loss to attempt toexplain it on the basis of any of the known phe-

nomena of physics' or chemistry.These fundamental life processes are exhibitedjust as fully and completely by the simplest bacteria

as by the highest plants and animals* All livingorganism.s, notv;ithstanding their diversity of formand appearance, must possess something in commonwhich gives rise to that peculiar characteristiccalled "life".

If th 3 fundamental life processes are dueprimarily to some specific configuration oftissues or membranes, then such configurationwould have to occur in every living organism,including the simplest bacteria. Y/e find innature many structural uniformities which occurmore or less extensively among certain speciesof plants and animals, but these are the resultof evolution and v;ill be found to disappear aswe go down the scale of plant or animal life.Even the chromosomes which occur in the cells ofall higher plants and animals have never ^03onobserved in any of the bacteria, and thereforecannot be regarded as th-e primary and originalcause of the fundament^-! life processes. Itwould not be justifiable, in the absence ofexperimental proof, to assume that chromosomesor similar structural complexities exist inbacteria, merely because they have been observedto exist in the cells of the higher plants andanimal s

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3.

That the fundamental life procossss must"be duo, either wholly or partly, to specificchemical structures is generally admitted, hutthere is a pr availing opinion that the molecularstructures which are necessary for this purposemust be extremiCly complex. The failure of allprevious efforts to devise some type of molecularstructure which would function in a mannersimilar to the fundamental life processes doesnot, hov/ever, prove that the solution of theproblem must lie in the direction of extremecomplexity. The complex molecular structuresof which the higher plants and animals arecomiposed have developed gradually in the courseof evolution, and the fact that they are necessaryfor the proper physiological functioning of theparticular organisms in vjhich they now occur.;-does not prove that they v^ere also the originalcause of the fundamental life processes in themore primitive ^'xrganisms from v/hich these higherplants and animals have developed. If extremelycom^plex molecular structur3S v-^ere necessary forlife of any sort, then it vfould he highly im-prchabl e that life could ev 3r have originatedspontaneously.


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4.

The Ch3mic^l Basis of Life.

If life cannot bo due, prirr.arily, either tospecific arrangaments of tissues or inemToranes orto extrernely complex molecular structures, thenit must be due to some comparatively simpleprinciple of chemistry vrhich has not yet beendiscovered. To find a cluo to this we must in-vestigate the molecular structure of prot3ins,because those constitute practically all thestructural material in the bodies of the simplestunicellular organismiS after removal of the vat 3r,Althougl': small amounts of fats ar ^ also present,yet these do not constitute structural materialbut appear to be merely the by-products ofcertain kinds of protein metabolism.

Protein substances, upon hydrolytic decom-position, always yield a mixture of amino acidsor their dik etopip erazine derivatives. To thealpha carbon atom of these acids thsra is alv/aysattached one amino group and one hydrogen atom,and usually also a more complex group, so thatthey may be represented generally as foilov/s:

ITH2-CKR-CO-OH.The structural formulae of the more im-portant ar;:ino acids are as follows:


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5.

Glycine COOHt

HCH

Alanine

Serine

ITHo

Cystine HGOCt

HgN

Aspartic acid


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Oxyprol inaHOCK

6.

CH.

CH.

COOKf

CH

Glycine-prolin 3 anhydride(E. A"b4erhald*n & 15. Komrn,Z. physiol. Ch-TH., 145, 308, 19.^5.)

Hp,Q

K^C

/CO CH/TJ\ CH

CH.

^UK

/CO

Glutamic acidHOOC-CHg-CHg-

COOK!CHt

ITK^

Ornithine COOKf

NHg-CK^-CHg-CHg CHrlHo


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HistidinoCCOH/ C-CKo CH

hi: I " CH "^ "^

Arginins

ITH

Caprins COOHf

CH3-CK2-CH2-CH2 CHITHo

Lysin3 CCOH!

H2N-CH2-CH2-CK2-CH2 CH^2

Valina COOKf

" CHCKCH3 .CH3 \jMHo

COOK>TH^^ C-m--CH2-CH2-CH2--CH


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L 3Ucin3

8.

COOHCH.CH.

CH-CKo2 CKtIso-] 2ucin3

CCOKCK^-. CH-CHs-CK^'-

OHT.TTT

Phanyl - al r.,nin 9H

HC - CCC '^'H

.C-CKg-COCKf

CHf

TyrosmaH

HOC C'

C -H

H'I*^

CHC Uj.Xo'

COOHCH


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9.

Tryptophp.n 3 H COOK- C :.,^ 'HC ^ '^- Q- - C~CHp OK

ii i if "^HC /-C . CHH i]H

t

Leucin3-gluta,!i]ic .cid .anhydrida(p. A. L?vin3 & W.A. Beatty,Ber. 59, 2060, 1906.)

^, CO ITIi^ ^ CK3HOOC-CHp-CK^-CH'" ^Z. CH-CHp-CH ^^ ^ -^ i:tT CO -^ ^ -^ CH3Valyiz-leucine

(?:. Abderlial den, Z. Physiol. Oh 3m.,131, 284, 1923.)CH^ .CO :iH .^ ^. CH3^^ CH- CK : '^ CH- CHg - CH '"CH3 "" ""mi CO -^'^ ^^^^ CH3

Leucine anh^.^dride(E. Aoderhalden & K Punk,

Z. physioi. Che-T,. 53, 19, 1917.)CH^ CO KH^ ,,.CH3'"'^

CH- CHp - CH'^' ^ CH- CHo - CH "CH^-^' ^ irn CO "" ^ "^"CiHj


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10.

Th3S3 amino acids will readily cond-Dnsc,v/ith the 3liTnination of water, to form eithsrchain structurss known as polypeptides, or ringstructures knovn as dik etopiperazines .(Smil Fischer, Unt 3rsuchung 3n liber Aminos^iuren,Polypeptide, und ProteSne, 1899 - 1906;Plimr::er's Chemical Constitution of the Proteins,Monographs on Biochemistry, Longmans, 1912)3 NHg-CRK-CO-OH =

im2-CRH-C0-!'^-CRK-C0-lTK-CRPI- CO-OH + 2 HO;2 NHg-CRH-CO-CK =

CRH CO,,^HN ^^IIH + 2 H9O"^CO CRH--^'' ^Since protains constitute the principalstructure-lDuilding food for animals, and upondigestion are decomposed into amino acids, in

v^hich form th 3y are assimilated by th 3 tissues,it is gensrally thought that the phenomenon ofgrovjth involv 3S condensation processes of asimilar character.

The frequent occurrence of diketopiper-azine rings among th 3 disintegration products ofproteins seems to indicate that this may be theform in which the alpha am.ino acid groups occurin nature, but a fatal objection to this thsoryis that diketopiperazines cannot grow by con-densation with additional amino acid molecules.If our purpose is to solve th 3 problem of life,then the biological side of the probl 3m must begiven full consideration, and we should have butlittle patience with any theory which explainsonly the chemical but not the biological facts.


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II.

The polypeptide thoory teaches that theamino acid groups occur in nature in the form oflong polypeptide chains. This theory offers atleast a partial explanation for the phenomenonof growth, as well as for structural variation,hut in its present form is inadequat3 in th^\tit does not account for that definite morphologywhich is possessed "by all living organisvns, norfor spontaneous division with the transmissionof hereditary charact sristics to the progeny.

There is, however, another type of structure, namely the helical spiral, which retainsthe 3ssential characteristics of both the ringand the chain.


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12.

Polypoptids S-pJrals .

If W'3 as sum 2 that th 3 val?nci3S of thecarbon ato^ ar3 arrang3d like th s corners of aregular tetrahadroE, and that th 2 three val3nci9Sof tri-val ent nitrogen in amino compounds areabout 3qual]y distributed around an equatorialcircle, (vhich arrangement appears to b :- theonly on ^' that is consistent with rill knov/nchemical facts,) then the polypeptide^ chain maybe coiled around on itself so as to form a "h el i c al sp i r al h av ing sub s tan t i al 1 y th 3 s am 3di^jT:]eter as the diketopip erasine ring.

KO

^ /L J C7/

H-N \CHO

'/

n/ \R H

/ \R K

A polypeptide spiral in KaCl solu


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Th D nitrog?n atoms v.'ill appear in tv/o rovson opposit3 si^.3s of th3 ppiral , and the co^npl 3Xtid3 chain? r3pr3S3ntod by th s R's in th ? previousequations, as well as th 3 carbonyl gr-oups, wil]1 i.k 'Wis 3 arrang3 th3Tnselv3S along other diaTri3tri-cally opposite lines. Chsrr.ic^J. union will probablytak3 place b3tw3en th 3 succes?iv3 nitrogen atoviisby virtue of th3ir fourth and fifth valenci3S,and p3rhn.ps also betv^een th 3 successive carbonylgroups in the manner sho^.vn. The nitrog3n atoms atth 3 3nds of the spiral will probably units withth 3 ions of inorganic salts, th 3 pr3Senc3 of whichis n3C3ssary for th3 nourishmsnt of all livingorganisms. It will b? found upon actually con-structing this spiral of atomic models that thECsis ^mpl ? room for th3 complex sid3 chains R if thefourth valency of th 3 alpha carbon atom is occupi3dby hydrog3n, but that th 3 pr3sence of rnoT 2 complexgroups in this position would make the spira]structur3 impossible. We find, hov;e-B3r, that thedecom.position products of proteins always have ahydrogen atom in this position.

It will be observed that the polyp 3ptidespiral in the accompanying diagram has an 3xposedamino group at one end, and an exposed carbonylgroup at the other end. Th eor 3ticall y it appearsthat additional amino acid radicals could be add 3dto eithsr end of th 3 spiral, although there maybe some at pr3sent unknown reason why growth cantake place at on 2 end only. A spiral with anexpos ?d amino group at th j free end may be d3sig-nated as positiv3 { + ), and on3 with an 3xposedcarbonyl group at the fr3G end as negative (-).A distinction should also b j made betw3en right-hand 3d (r) and left-handed (l) spirals.


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Th 3 similarity in forTj and app 3aranc : of apolypeptide spiral to a "bacillus or a spirillumwill be apparent. It should be capable of graving-endwise by condensation with additional amino acidradicals, and as long as tho spiral form is main-tained the structure will possess definite mor-phology. It must remain permanently right-handedor left-handed which appears to account for theoptical activity always s^Libited by substancesobtained from living organisms. It should becapable, during growth, of acquiring differentarrays of side chains upon being nourished withdifferent kinds of amino acids, and thus exhibitthe characteristic of variability. It would not,however, upon division, be capable of transmittingto its progeny any permanently inheritable ch ' racteristics, and can therefore not be regarded as acomplete living organism.


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15.

The Linking of Pol ypeptide Sp i rals

Since th ^ distance between the centers ofadjacent carbon atoms is about 1.54 x 10" cr.

,

the diameter of a pol;>'p ept ide spiral, as measuredbetween the centers of the ^toms, would be ^bout?.l X 10~ cm. It will therefore require severalhundred spirals arranged side by side to producean organism^ at large ^s the sm.a]lest visiblebacillus, whijQh m2asure3 about 1000 x 10"^ cmin diameter. In order that the organism maypossess definite individual characteristics, thesespir'-Qs would hav b to be coupled together in somepermanent m.anner, but after they are thus coupledtog 3th er, they will have a tendency to preservetheir arrangs-ment throughout growth, and if trans-verse fission occurs, each portion would hav3 tocontinue growing according to the originpJ pattern,There will thus be exhibit 3d, in the simplestpossible mann3r, a proc3ss of inheritanc3 by vmichparental characteristics are preserved throughoutgrowth and transmitted to th 3 progeny.

It appears that there ar 3 only a limitednumbsr of ways in which adjacent spirals canbe connect 3d tog3th3r. The connecting ccm.plexesmust be conparat iv 3I y simple, b?caus 3 if morethan a cert^^in number of int srmiDdiat 3 atoms arepr3S3nt their m.ovBmonts v:ill no longer bedefinit3ly coordinated so as to form th 3 r requiredint3rmediat3 structures, but will b3 m5r3 or 1 3ssat random. In ord3r to d?t3rmin3 the nature ofthes3 conn3cting complexes, th 3 use of atomicmodels is r 3ccm.mend 3d, b'^caus3 the probl 3msencountered hsre ar 3 structural rather thandynam.ic .


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Th3 form ofmost fraquontly inconn Oct ion lD3twienof a C3ntra] ^^arbowhich aro usua]lyatoms of amino acifrom such connsctia study of proteintwo typ^s of suchpro t 3 ins

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connecting complex which occursnatur3 appears to be a triplethrcD adjacant spirals by m, 3-^nsn atom. The compl 3X groupsattach 3d to the alpha carbonds arc 3vid3ntly the fragmentsng comp] exes. It appears fromd 3composit ion products thattripl 3 connections occur in

Leucine, phenyl -al an in e, and tyrosine havea triple junction at th 3 gamma carbon atom, withan intermediate -CHo- group between this triplejunction and the -CH IHig-COOH group. The completetripl 3 junction, (assuming it to be the same onall thr3e sides,) tog 3th er with one-half of eachof the three adjacent spirals, will thereforeapp ear s omi ewh at as follows:

OC MI\\ CHCH^

CHCH, CK,

1^: CH CH COCO HF

A triple junction of the gamima-gamma-garrima type.


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which liii r P^^-:^^y ^'-^- typ. of trip! 3 junctionwhichwill form most rs-'^.dily in naturo. b^causo ifthev wn,nT>;^'^'; "'''2- groups W3re introducadthey would have too much f r -dom of mov 3m 3nt toproduce the triple junction spontaneously. Hydro-carbon chains will not react with 3ach oth^r ^fthey are capable of movement at random in any^wnnTr^""'''.^''? ^^^^ '" ^^^^ ^^' condition whichwould exist at any point biyond th3 gamma carbon

-^A. "^^* 2" "^^^ 0th 3r hand, we omit some of thxntarmediate-GHg-^- groups and attempt to form thetriple junc-:ion at the b3ta carbon atom thspirals will have to b3 brought so cl.os3 togeth-rthat there would probably be considerable repul-sion betwaen them due to th 3rmal vibration of thatoms. Such a triple junction could prooably notform spontaneously unl 3ss the spirals were crowdedtogether from the outsida, but the prssence ofsubstances like iso-leucins and valine ^Tiong thdecomposition products of proteins seems to showtnat triple junctions of the beta tyiDe do occurat times.The existence of both beta and g=^mma junc-tions in the same prot 3in is indicated by the

occurrence among protein decomposition productsof^ substar.ces like val yl -1 eucin 3 which containsa beta junction at one end nf the rnol ecul 3 anda g^mma junction at the other end.If W3 connect togeth3r a lar/^3 numb 3r ofspirals by means of triple junctions of eith srthe beta or ths gamma type, th ay will formcoll ectiv sly a cluster of hexagonal compartments.


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18

The cellular structure of proteins.In living tissues these will "be filled with wateror dilute salt solution, and it will be observedthat the vacant spaces in these compartments havea combined cross-s ection


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19.

A AH CHCHpCH,

CH CH

A cluster of thr-ae polypoptide spirals witha coTi]pl-3t3 tripl3 junction at th 3 canter ought topossDss all th 3 fundarn Bntal characteristics oflife, provided it is equipped with a stable outerstructure. A group of three hexagonal compart-ments as illustrated on tha precedirg page couldprobably not exist in nature becausD each com-partment would have three exposed corners whichwould rander it very vulnerable. Regardless ofhow many additional compartm3nts W3 add to thisstructure, the m^aximum numb sr of exposed cornerscan nevsr b ; less than two. But at th surfaceof the organism th3re is really no nscessity forconfining ourselves to the use of hexagons. If,for example, we form th 2 surface structura ofpentagons instead of hexagons, the number ofexposed corners on aach compartmant would be re-duc 3d to one, and our organism v;ou] d appear incross- section somewhat as follows:


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Cross-section nf a simpl 3 living orgnnism,Perhaps cystine, which occurs in small

aTTiounts in the dGcompcsition products cf illproteins, forms part cf this surface structure.


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21.

Direct Ch -smical Union "b 31 ;v o jn Sp i r "^J. r-

.

Ws hav3 har-atnl'crs aGSurnad that c^nnDction"between adjacent spirals t.ak^s plac3 only throughthe hydrocarbon side chains attached to the alphacarbon atcms. This is undoubtedly the priir.arymode of connection, but af t :r tv/o spirals arethus connected together there may bj a secondaryconnection between th 3 arnino groups of on^ spiraland th3 carbonyl groups of the other. If bothspirals have the sa:!ne dirsction of twist, theamino hydrogsn cf on 3 spiral will b3 posit ion jddirectly opposite the carbnnyl cxyg i^n of th3 otherspiral, so that there will bo a tsndsncy for wat 3rto split ^ff, leaving the amino nitrogen to combinedirectly with the carbonyl carbon. In this mannerthere m.ay be produced either thj pyrrole or thepyrimidine ring, depending on wheth3r the primaryconnection was of the beta or of the gamma type.As shcv\rn in the follov/ing diagrams, various dif-ferent configurations can b3 produced by joiningadjacent spirals directly to 3ach other:

V-r^'


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A carbonyl carbon atom should "be abl o tounits in this mann2r with two nitrogsn atoms ofan adjacent spiral, and since it is already joinedto one nitrogen atom of th ? same spiral, thare willbs produced in this manner th? guanidine complexwhich occurs at one 3nd of the arginine rKolecuJe.The three intarmediate -CHq* groups of the argininemolecule are exactly the number that would occurin passing over to the next adjacent spiral if theintermediate junction is partly of the beta andpartly of the gamma type.

HCHCH

OC im

Arginine in situ.


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Conclusion.

The c^rractness of the above hypothesisdepends in n. ln.rge measure on wh eth 3r we werejustified in -ai^Jcing the assumption that thefundamental, life processes ar 3 inherent in themolecular structure of the proteins, and are netprimarily dep3ndent on any specific physicalheterogeneity. This assumption is clearly cr^n-trary to orthodox theories which attribute justas much importance to the physical heterogeneityof protoplasm as to the chemical comstitutionthereof, but the failure of orthodox theoriestc account for and explain th 3 fundamental lifeprocesses should be sufficient justification forattempting the solution of the problem on anew bas^.

The molecular structure of proteins v^illprobably never be established conclusively bychemical analysis n2one. It is, in fact, doubt-ful whether protein molecules are of uniform sizeand composition. According to the foregoinghypothesis protein m.oleculos, when dissolved inwater or dilute salt solution probably consist ofplatelets of irregular form and size which havebecome separated from a cluster of hexagonal com-partments. The methods of analytical chemistrycan tell us only what the fragr^ients of proteinstructure are and what the elementary compositionthereof is, In order to find out how these frag-ments were joined togethsr we miust take intoconsideration the principles of biology, althoughafter a certain scheme has been suggested, wemay determin3 the probable correctness th3reofby comparing the elementary composition of suchhypothstical structure with that found experi-mentally.


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All proteins, (v;ith the oxc option of prct-R-mines and histonos, ) hav::; apprcxitnat oly thofollowing p3rc3ntag3 ccTnposition;Carbon Hydro g2n Nitrogen Oxygon Sulphur50-55 6.9-7.3 15.0-19.0 19.0-24 0.3-2.4

If WD takG, as a roprosentativ o sample ofour hypcthotical substance, a compl ot o triplajunction of the gamrna-gamrna-gi^jTiTTia typo and cn3-half of oach of th 3 thr^e adj ac 3nt spirals, th onthe orapirical formula th3r3for may b: dorivodas follows:

/co\

H3This will give the following percentage composition:Carbon Hydrogen Nitrogen Oxygon53.8 5,8 18.8 21.5

The values thus calculated are in fairlyaccurate agreement with the exporimental values,except that the hydrogen is slightly low, but thatis just what would be expected because of thedifficulty of obtaining proteins in perfectlyanhydrous condition. Another possible explana-tion for the low hydrogen percentage is that theprotein molecule in v/at er solution may consist ^fonly a thin sheet t^iken transversely of the ax 3Sof the spirals, so that many additional hydrogenatoms or hydroxyl groups v/ill b^ requirod forcombination with the free ends of the spirals.For exo.mpl e, if wo include only tw^ additionalhydrogen atoms in our th3cr?tical formula, theporcantago of hydro g on will bo brought up to thevalues obtained 3xp or im entail y.


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If v; D n,ssu-ai^ the tripl 3 juncticn tc "be onlytv/c-thirds gninir.^.. and on-3!-third bota, th Dn theporccntago composition will b 2 -is follows:Carhrn Kydrcgcn Kitrcg an Oxygon52.1 5.2 20.1 23.1

Inst3ad of dealing vrith absoluto p 3rc ant ag dsof th3 various elDments, it is b ott ^r to dealwith ratios of carbon tn nitrogen, bocauoo theratio of th es a two values will b l^ un-^ffected byvarying ^^jmounts of v^ater that may be present, crby the extra hydrogen that rno,y be attached to thefree ends of the spir-^2s.

From the above theoretical d'lta wo obto.inthe following ratios of carbon to nitrogen:With triple junctions of theg 'iTDTna- g ^xn-ra -'.- g arnma typ e

,

With trljftl e juncticns of theb :^t a-g aTP.ma-g omrna typ e

,

With quadruple juncti':nsof the type:

2.86

2.59

^CK CK 2.14X.

With quadruple juncti'-nsof the type

CH CH" CH2CHo

3.00


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No att 3Tnpt h-i.s bo on mad j horjinabrva toexpl'iin the chrcT.oscir.o mechanism in det'^.il.ChrcrnoGoiTGS dc not occur in the simplestorganisms such as the bactaria, but app 3'\r tobo th3 first stago in ovoluti^n to high ortypos, whorsas the purpr^so of th o prosonttreatise is to oxp] ain 1 if o processes onlyin so far as they aro of universal occurrenceand common to all forms of life.

.-7/.

^:^t^JC u^iux

C^bilLX^ Vo^ o 'o/.

^l


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Krafft SpiralMolecularStructures TheBasisOfLife 2nd.ed

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Transcript of Krafft SpiralMolecularStructures TheBasisOfLife 2nd.ed