Paul J.
Flory Macromolecules Vis-a-vis
Stanford University
Stanford, California 94305
the Traditions of Chemistry
Polymeric substances are distinguished at the molecular
level from other forms of matter by the concatenation of
atoms or groups in chain-like sequences, often of great
length. The structural units that identify various poly-
mers, natural and synthetic, include the gamut of possi-
bilities in chemical constitution afforded by methods of
synthesis, in uiuo and in uitro. Yet, the structural motif
common to all of them is the sequential connection of
units, of whatever description, in chains. Linear polymers
consisting of a single sequence or chain command fore-
most attention. However, branched and cross-linked
structures, and even three-dimensional networks, are in-
cluded as well. Inasmuch as points of branching or of
cross linking generally are separated by fairly long linear
sequences of units, the covalently linked chain remains
the characteristic structural feature even in so-called non-
linear polymers. Consistent with this generalization is the
fact that covalently bonded two- and three-dimensional
arrays typified by graphite and diamond are customarily
excluded from consideration as polymers.
Reflecting on the ubiquity of macromolecular materials
on the one hand and the scant attention given them in the
undergraduate chemistry curriculum on the other, an in-
quisitive student might raise questions like the following:
Does the type of structure of matter occurring in polymers
depend upon some principle alien to the body of chemical
science? Is this broad class of substances, collectively, an
aberration extraneous to the central bodv of facts and
principles comprising chemistry? Or, is the rational inter-
ret tat ion of macromolecules so difficult. intrinsically, that
they are intentionally excluded from the fare for inder-
graduates? On the contrary, can they be so readily com-
prehended by straightforward deduction from laws and
rules laid down for small molecules as to obviate anything
more than superficial mention? Do the manifold applica-
tions of polymers, in industry and in biology, disqualify
them as objects of pure scientific inquiry?
In response to questions such as these, it could he
~ o i n t e dout, first, that the occurrence of macromolecular
bubstances is implicit in the rules of valency and chemical
comhination. At a most rudimentary level, the very idea
of multivalency and the capacity of certain kinds of atoms
-notably carbon, sulfur, nitrogen, oxygen, silicon, and
phosphorus-to enter into sequential combinations raises
the possibility of chain structures. Simple examples illus-
trating manifestations of this possibility are common-
place: the n-alkanes, elastic sulfur, and polypeptides. If in
fact multivalent atoms refused to enter into sequential
combinations, or if this propensity did not manifest itself
in the occurrence of macromolecules beyond some finite
limit in length, it would be obligatory to introduce a qual-
ification to this effect early in the exposition of conven-
tional chemical doama. Thus, given the rules of valencv
governing chemicai combination, if long chain molecule^
com~risinetens or even hundreds of thousands of skeletal
atoms linged in sequence did not occur, then the chemical
rule forbidding their existence would need to be set forth.
Clearly, such a rule does not exist. Hence, if we are to ig-
nore the implications of multivalency and consecutive
bonding of atoms as manifested abundantly amongst nat-
ural and synthetic polymers, then the rationale behind ex-
732 / Journal of Chemical Education
clusion of these suhstances should he explicitly made
known.
Logically, then, the occurrence of polymers is implicit
in the elementary principles of chemical bonding. It is
noteworthy that the chemical bonds in polymers are
equivalent quantitatively to corresponding bonds, similar-
ly situated, in small molecules. Within limits of measure-
ability, their energies are identical. The same holds for
bond lengths, bond angles, and force constants. Constitu-
tive properties of macromolecules can therefore be formu-
lated from the same information as for small molecules.
The two regimes are continuous; no definable boundary
separates one from the other.
So much for the logical foundations of the area of
science having to do with polymers, and its coherence
with chemistry as a whole-if we regard chemistry as the
science that deals with matter a t the molecular level. It is
of interest to examine the historical record in regard to
the foregoing assertions to the effect that the occurrence
of macromolecular forms of matter is implicit in elemen-
tary ideas concerning valency ( I , 2). The concept of valen-
cy took form in the work of Frankland around 1852. Quad-
rivalency of carbon was enunciated by Kekul6 and by
Kolbe in 1857. Kekul6 pointed out in 1858 that carbon has
the capacity to use one of its valences to combine with an-
other carbon atom, and thus to build chains. His textbook
of 1861 has been said to mark the heginning of carbon
chain theory. His celebrated ring formula for benzene ap-
peared four years later.
The graphic formula, that particularly facile device by
which valences are represented by lines drawn between
symbols for atoms, was introduced by Couper in 1858. It
was adopted shortly thereafter by others, including Crum-
Brown (1861), Wurtz (1864) and, with variations, by Ke-
kul6 and Loschmidt (1861). The graphic formula a t first
was primarily a topological device denoting connectivity
between atoms, and especially the integrity of groups
which was a foremost concern of chemists of that era. Its
geometrical significance in defining the spatial relation
between atoms emerged gradually, and bas continued to
evolve up to the present in stereochemistry, structural
chemistry, and conformational theory.
The implications of multivalency and its embodiment
in the graphic formula are readily apparent in retrospect.
To what degree were they evident to chemists at the time
those important concepts emerged? Answers to questions
of this kind must be sought by reading between lines and
therefore are to some extent conjectural. The idea of poly-
condensation and its application to yield polymers of a
degree n as expressed in formulas such as H-
(OCH2CH2)n-OH and in H-(OCsH&O),-OH, are re-
corded in the period 1860-70. Other condensation polymers
were prepared, and while their molecular weights doubt-
lessly were low by present standards, their basic linear
chain structure was clearly recognized in a number of in-
stances ( 3 ) . However, the foundations of organic chemis-
try were not sufficiently secure a t that time to sustain the
extension of them to polymers of high molecular weight.
Moreover, physical methods for measuring molecular
weights were unknown before 1885. I t is not surprising
therefore that possibilities in this direction were not vigor-
 ously pursued in the era that marked the dawn of struc-
tural chemistry.
Interest in the synthesis and investigation of high mo-
lecular weight compounds all but vanished from the scene
for the next forty to fifty years, due in large measure to
two independent trends. First, the molecule and its repre-
sentation by a concise graphical (or structural) formula
became the prime object of all effort. By tacit assumption
every pure substance worthy of investigation could he rep-
resented uniquely by such a formula. It was incumbent
upon the investigator to specify a formula devoid of amhi-
euitv
" ~, for even,. (oure)
.. . chemical substance. Polymers Ken-
prally comprise mixtures of homulogous species und hence
are described hv mol~culardistributions. Moreover, a long
chain must bear end groups, determination of which
would have overtaxed available analytical methods of the
times. The formula could not be completed without speci-
fying them. For these reasons, polymers could not he fit-
ted easily into the accepted scheme.
Secondly, colloid chemists of the era asserted that all
colloidal substances are aggregates of smaller species.
Their judgments went unchallenged in most quarters.
Since polymers, both natural and synthetic, are colloids
according to the quite proper definitions introduced ear-
lier by Graham, they too must he aggregates. Some, such
as W. Ostwald, relegated the molecule to a strictly suhor-
dinate role in the hierarchy of structural entities at the
suhmicroscopic level. In this respect, his views and those
of his numerous following were diametrically opposed to
the outlook evolving in chemistry as a whole. However, a
larger conflict was avoided by tacit limitation of each view
to its own domain: molecules for low molecular suhstances
and colloids for large ones.
By the end of the nineteenth century a considerable
number of polymers actually had been prepared, often in-
advertently, by bifunctional condensation. That the prod-
ucts were in fact polymers is clear from the properties re-
ported. With rare exceptions, however, they were repre-
sented as cyclic monomers or dimers. Aggregation was in-
voked to explain their "colloidal" properties. (3).
Although a numher of vinyl polymers had been stu-
mbled upon in the course of investigations of their mono-
mers (some of them before 1850), their constitution was
unknown. Like the imagined cyclic molecules above, they
were regarded as colloidal aggregates held together hy
mysterious "secondary valences."
The elucidation of naturally occurring polymers, viz.,
ruhher, rarbohydrates and proteins, presented morc suh-
stnnti\.e dilfirulrie~.In the period 1870-1900 earh of thew
classes of pol\mers was the sut~jectof intensive in\x!;tip-
tions, conducted on the respective classes by separate
groups of investigators working quite independently. The
complexities of the repeating units comprising these poly-
mers resisted determination until after 1900, and in this
circumstance a definitive grasp of their constitution was
precluded. The relationship of isoprene to ruhher and of
amino acids to proteins had long been known, but the
structures of the corresponding units in the respective
polymers had first to be established, the former through
the investigations of Harries (1904-14) and the latter
through the work and inspiration of many investigators,
notably Fischer (-1906) and Hofmeister (l902), cf. seq.
The structural units of carbohydrates were even more
recondite because of their greater complexity and their
stereochemical ambiguities. The structure of the anhydro-
glucose unit C6H1005 was not fully established until 1928
(Haworth). Yet, the role of this unit in starch and in cellu-
lose was recognized, and even during the 1880's formulas
(C~HIOOJ),where n = 100 were suggested for "amylodex-
t ~ s from
" starch. Whether or not the units were cov-
alently bonded was a question which did not require an
explicit answer a t the time, hut i t seems clear that some
authors, at least, had molecules in mind when presenting
their formulas, often supported by primitive determina-
tions of molecular weights. All this was changed with the
ascendency of the colloid apostasy in the early twentieth
century. Natural polymers, like their more obscure syn-
thetic analogs, were declared to he physical aggregates of
smaller molecules held together by secondary forces, of
origins unidentified. Not until the 1920's and 1-ter did
their molecular nature come to he recognized ( 3 ) .
The history of concepts concerning the nature of pro-
teins, vividly portrayed by Edsall (41, offers an especially
interesting paradigm of the evolution of ideas concerning
macromolecular suhstances. The number of proteins iso-
lated, purified, and crystallized before 1900 is truly im-
pressive. In 1885 Zinnoffsky arrived at a (minimum) mo-
lecular weight of 16,730 for horse hemoglobin on the basis
of careful analysis of its content of iron. Colligative meth-
ods for determination of molecular weights, originating in
the work of Raoult (-1885). were a .~.o l i e dto ovalbumin.
hemoglobin, and serum albumins during the succeeding
20 vears. Molecular weiehts
" of the order of 15.000 or -areat-
er were indicated, hut the results came to he discounted
on the grounds that the solutes were colloidal and there-
f o e beyond the purview of the laws of physical chemistry
applicable to solutions of "crystalloids."
The polypeptide hypothesis was offered in 1902 by Hof-
meister as the only plausible bask on which to explain the
chemical properties of proteins (4). Fischer subscribed to
the same view and, in its support, undertook the task of
synthesizing polypeptides. His preparation of a molecular-
ly monodisperse polypeptide having a degree of polymer-
ization of 30,stands as a monumental achievement. He
did not, however, envisage polymers of greater chain
length in proteins. In keeping with the outlook of the
times, he preferred instead to regard proteins as aggre-
gates of shorter polypeptide chains.
Even apart from the questions of molecular weight and
of secondary aggregation of short chains to make up the
protein particle, the polypeptide chemical strllcture was
not universally accepted for nearly 30 years after its in-
ception. A number of chemical combinations were pro-
posed for the primary ingredient of proteins by organic
chemists during the mid-1920's in a frenzied effort to find
an alternative to the polypeptide (i.e., polymeric) hypoth-
esis. These alternatives were cyclic compounds of various
sorts (diketopiperazines, a110 forms and other more esoter-
ic heterocycles). They were presumed to be joined by
aggregation in some mysterious way not specified. Finally,
a plea for sanity in recognizing elementary facts of protein
chemistry was eloquently voiced by Vickery and Osborne
(5) in 1928. The polypeptide theory gradually gained
. -
ascendencv thereafter. the remenance to chemists of
polymeric~tructuresin substances as intimate as proteins
notwithstanding. Even Vickerv and Oshorne (5) (P. 419)
quailed at the-specter of polypeptide chains ha&g as
many as 500-600 units. This prospect, if proven to he cor-
rect, would in their view raise "difficulties." Although the
nature of the difficulties foreseen was not made clear,
they may have concerned the exact specification of the se-
quence of units in a chain of such length.
The saga of polynucleotides is fascinating also, but will
not be recounted here in detail. It must suffice to point
out that these polymers, exceeding in chain length any
other linear macromolecules characterized to date, were
thought to he tetrameric until the mid 1940's. The fact
that the Watson-Crick model for double-stranded DNA
was put forward only a few years thereafter (1953) is sig-
nificant. The publicity it has received seems to have oh-
scured preceding events that were essential precursors to
this important advance.
It would be incorrect to place most of the blame for the
prolonged delay in the acceptance of the molecular view-
point regarding polymers on the dogma of colloid chemis-
try around the turn of the century and during the fol-
Volume 50, Number 1 1 . November 1973 / 733
lowing three decades. Probably of even greater importance
was the reluctance of chemists to consider seriously mac-
romolecular formulas and to face the associated obscuri-
ties of molecular distribution and end groups. Lack of the
capabilities in earlier times to resolve these aspects posed
genuine difficulties. The doctrines of a former era in col-
loid chemistry were eventually cast aside, hut a distant
attitude toward macromolecules continues to he wide-
suread amonest chemists even today.
'The traditional aversion of chemists to forms of matter
that cannot he represented by a unique formula doubtless
is rooted in the historical recited ahove. Their
preo'ccupation with small molecules during the latter part
of the nineteenth century and the early part of this one is
readily understandable, as discussed previously elsewhere
(,3~) . ,The uoint that concerns us here is the fact that the
character of chemistry, nourished by spectacular success-
es. eelled in this era. In particular, the one-to-one associa-
tion between formula -and substance was firmly en-
trenched by the time chemistry became a discipline. Mac-
romolecules are not easily accommodated in this scheme
without basic revisions, as pointed out above.
It is especially to he noted that the basic pattern of
chemistw was established prior to the appreciation of the
molecul~rnature of po~ymkrsand to faGulation of prin-
c i ~ l e sand theories describing their hehavior. The field was
sibdivided along lines that largely persist today. Polymers,
being in eclipse at the time, did not find a place in the
syllabus, apart from some desultory entries on colloids.
In more recent times, the dominance of the deductive
approach to chemical science has directed attention large-
ly toward the simplest of molecular systems. The reduc-
tionist view that all matter, animate and inanimate, is
governed by the same set of fundamental laws can scarce-
ly he challenged. But the corollary usually inferred from it
to the effect that a tractable conceptual framework for
understanding and interpreting the hehavior of complex
systems including biological-even sociolagical-ones can
he deduced from these laws, is fallacious. In recent years
much of chemistry (and other branches of natural science
as well) have fallen under the spell of this misleading no-
tion. To he sure, a great deal can he learned by investiga-
tion of the simplest systems, hut comprehension of the
next level in the hierarchy of sciences cannot he achieved
through straightforward processes of deduction alone. As
Anderson (6) has pointed out, the same creative insights,
generalizations, etc., are required at each leyel. Thus, it
should not he assumed that full knowledge concerning
simple molecules will pave the way for comprehension of
macromolecules without further creative effort, formula-
tions of new concepts with appropriate abstraction, etc.
This is not to say that information gained in one do-
main cannot he applied in the other. The debt of polymer
science to knowledge gained from the study of small mole-
cules is very great. It is also true, however, that investiga-
tions conducted on macromolecular systems have enriched
chemistry as a whole. Our understanding of chain reaction
kinetics, of free radical and ionic reaction mechanisms,
and of thermodynamics of solutions has been advanced
and enlarged by investigations on polymers. As other pa-
pers of this symposium testify, a wealth of illustrative
material is available from current knowledge of polymers
in these areas and others including chemical statistics,
stereochemistry, conformational hehavior, and statistical
mechanics.
As a consequence of the pervasiveness of the deductive
viewpoint, chemistry has come to he regarded in some
quarters, and even among some chemists, as a sub-disci-
pline of physics on the one hand and the handmaiden of
hioloev on the other. Close connections with both these
disciplines and a deprndenry on physics do indrwl exisr.
Culri\.ation oi the ronrinuum oi knowledge between phys-
ics and chemistry has certainly been to the henefit of
734 / Journal of Chemical Education
chemistry. But to hold that all chemistry follows deduc-
tively from physics and dismiss the matter therewith is to
overlook the central role of science in erecting constructs
for representation of physical reality in terms rational to
the human mind.
Elementary textbooks of chemistry seem to have been
influenced overwhelmingly by the reductionist doctrine, or
rather by its converse, "deductivism." The current fashion
is to develop the subject largely from a set of rules. These
are often introduced by appeal to physics, and to atomic
physics in particular. The connections with these fields
should certainly he emphasized at the proper stage in the
student's development, hut to present chemistry as a de-
rivative science is to conceal the historical foundations
and concentual framework of the science of molecules and
molecularbehavior. This viewpoint could conceivably lead
ultimatelv to denial of the rightful
- existence of chemistry
as a separate discipline.
An examination of elementary texts of physics and
chemistry brings to light a striking difference in pedagogy.
In the former, principal topics-heat, light, mechanics,
etc.-are introduced with a brief discourse on common
observations and experience related rher~to.The srope of
rommonplaceexperienre may then he enlarged 1)). preienta-
tion of observations under idealized conditions. i.e.. hv cita-
~~ ~~ ~ ~ ~
tion of experiments, or by prrftmnunce of demonstrations.
This is followed hv zeneralizatiun and d ~ r r l w m e n of
t con-
cepts with some degree of abstraction. Most df the subjects
treated in elementary chemistry texts, on the other hand, are
removed from common experience. The traditional choice of
subject matter offers little opportunity to commence with
examples familiar to the beginning student. It is almost as
if chemistry and its chemicals are from another world,
i.e., from the occult world of the laboratory. Perhaps cog-
nizance of the most commonplace materials of man's en-
vironment, indeed of man himself, if introduced appro-
priately as a part of the scientific scenario, would contrib-
ute a welcome note of relevance.
With large numbers of students inclined to enter the
biological sciences and medicine at the present time, the
importance of connections between polymer science and
biology should not he overlooked. This interdisciplinary
area is grossly underdeveloped. It seems self evident that
polymer science should furnish the medium for interrelat-
ing chemistry and hiology. The gap between these disci-
plines cannot he effectively bridged without recourse to a
rigorous conceptual framework for dealing with macromol-
ecules in general. The often implied view that hiopolym-
ers are suhjects apart from the tainted materials of indus-
trv.
,. and hence removed from ~
~ ~ ~
. o l.v m e science
r as currentlv
misunderstood rests on supposirions and regrertable mis-
ronrentimx. \Vohler's swtheais oiurea a rrnturv and a halr
ago d;d not destroy the'hoctrine of Vitalism! ~ n f a c tbiopo-
,
lvmers manifest all of the properties of synthetic polymers
i f less refined constitution; i o he sure,-they also &hibit
some important additional features for which they have
been specially equipped through eons of evolution. Never-
theless, they share much in common with "non-living"
macromolecules.
The frequent assertion that macromolecules are intrins-
ically too complicated, and therefore too difficult, to he
comprehended by undergraduates can he controverted on
either of two counts. First, and most directly, a wealth of
topical material is now available which, when put to test,
demonstrates the contrary to he true. Secondly, the judg-
ment of difficulty is necessarily subjective, being condi-
tioned by one's point of view and hence by the state of or-
ganization of knowledge (and one's familiarity with it) in
the given field. It is hardly an intrinsic characteristic of
the given area of interest. Complicated suhjects have re-
peatedly been made simple by improvements in method
and in point of view.
 Conclusion
I have endeavored to direct attention to the coherence
~~~ ~ ~~
of the scientific aspects of macromolecules with the chem-
istry of small molecules, and to the close connections be-
tween the two domains. These observations, augmented
perhaps by the key importance of polymers both in biolo-
gy and in industry, should support cogent arguments for
accommodating macromolecular science within the disci-
pline of chemistry, and hence for incorporating the
subject into the core curriculum. However, the content of
a discipline and its associated curriculum may more oflen
he determined by precedent, i.e., by historical accident,
than by logical considerations. Hence, I do not offer these
remarks with any substantial expectation that the ideas
they are meant to express will have much influence on the
future character of chemistry, even if a consensus were to
grant them validity.
If, despite these forehodings, and for reasons unforeseen,
macromolecules were to be brought into the chemistry
curriculum in the near future, then a vigorous plea should
be entered that the treatment due them he integrated into
the logical exposition of the discipline. As remarked ear-
lier, the occurrence of macromolecules should he intro-
duced as the embodiment of the principle of multiple va-
lency and consecutive bonding. This aim should be met
irrespective of the level of sophistication adopted for
treatment of the chemical bond. The subject of macro-
molecules should not, ns a t present, be introduced
through an awkwardly inserted chapter late in the text.
The opportunity to develop the suhject logically as a part
of the whole having been forfeited, the introduction of the
~~
subject so belatedly must perforce be justified by scienti-
fically extraneous remarks on the technical importance of
polymers, replete with statistics in tons per annum. Bet-
ter to ignore the subject altogether than to offer it on
these grounds in a course purporting to he science.
By this I do not mean to deprecate the importance of
the technological ramifications of the subject. These do
indeed enhance interest in, and the significance of, the
study of polymer science, and properly so. It is my opinion
rather that the subject should he treated first from the
detached standpoint of pure science, and preferably as an
integral part of molecular science (chemistry) of which it
is logically a part. One may subscribe unreservedlv to the
view that motivations and content in pure science-are un-
related to practical applications. I t does not follow, as
often is assumed, that a subject of practical relevance is
automatically excluded from pure science and ineligible
for abstract inquiry. Accordingly, i t is my view that poly-
mers should be introduced in the context of the constitu-
tion of matter a t the molecular level, or not at all.
Literature Cited
(1) Psnmgton. J. R., "A Shoe Hiatow of Chemistw," 3rd Ed.. MacMillan. London.
19Si.
(2) Lcicester, H.M., .'The Histotical Backgmund of Chemi~fry."John Wiley and Sons.
~~.~~~~~
New York 19FR.
(3) Flow, P. J., "Principles of Polymer Chemistry: Carnell University Press. Ithsca,
NewYork, 1953. Chsp.1.
(4) Edsall,J.T.,Arth.Biorhem. Biophy$., Sup& 11.12119621.
(51 Viekery, H. B.. and Osbarne, T.B.,PhyaioL Reos.. 8.398 119281.
(6)Anderson. P. W..Scirncr. 177.393 (1972).
Volume 50, Number 7 1 . November 1973 / 735