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Plant Macromolecules as Biomaterials
167
REFERENCES
1. Chen, H., Jia, Y. and Guo, Q., 2020. Polysaccharides and
polysaccharide complexes as potential sources of antidiabetic
compounds: A review. Bioactive Natural Products, [online] pp.199-
220. Available at: <https://www.sciencedirect.com/science/article/abs/
pii/B9780128194836000060> [Accessed 29 June 2022].
2. Domingos de Sousa, F., Rogênio da Silva Mendes, F., Jovanny
Bermudez-Sierra, J., Fernanda Brandão da Silva, A., da Silveira
Vasconcelos, M., de Fátima Goebel de Souza, T., de Oliveira Nunes,
M., Eufrásio Vieira-Neto, A., Roberto Lourenzoni, M., Diógenes de
Oliveira-Filho, R., Rolim Campos, A., de Azevedo Moreira, R. and
Cristina de Oliveira Monteiro-Moreira, A., 2020. Plant Macromolecules
as Biomaterials for Wound Healing. Wound Healing, [online] Available
at: <https://www.intechopen.com/chapters/69102> [Accessed 29 June
2022].
3. Manivasagan, P. and Kim, S., 2014. Extracellular Polysaccharides
Produced by Marine Bacteria. Advances in Food and Nutrition
Research, [online] pp.79-94. Available at: <https://www.sciencedirect.
com/science/article/abs/pii/B9780128002698000051> [Accessed 29
June 2022].
4. Mishra, A., Behura, A., Mawatwal, S., Kumar, A., Naik, L., Mohanty,
S., Manna, D., Dokania, P., Mishra, A., Patra, S. and Dhiman, R.,
2019. Structure-function and application of plant lectins in disease
biology and immunity. Food and Chemical Toxicology, [online] 134,
p.110827. Available at: <https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC7115788/> [Accessed 29 June 2022].
5. Su, L., Feng, Y., Wei, K., Xu, X., Liu, R. and Chen, G., 2021.
Carbohydrate-Based Macromolecular Biomaterials. Chemical Reviews,
[online] 121(18), pp.10950-11029. Available at: <https://pubmed.ncbi.
nlm.nih.gov/34338501/> [Accessed 29 June 2022].
CHAPTER 6
Functional Applications of
Macromolecules
CONTENTS
6.1. Introduction .................................................................................... 170
6.2. Chain Length Limitation and Up-Scalability Aspects of Discrete
Synthetic Macromolecules ........................................................... 171
6.3. Applications of Discrete Synthetic Macromolecules in
Material Science .......................................................................... 173
6.4. Self-Assembly of Discrete Synthetic Macromolecules ..................... 174
6.5. Foldamers Based on Uniform Macromolecules ............................... 175
6.6. Applications of Discrete Synthetic Macromolecules in Life Science 176
6.7. Other Applications of Discrete Synthetic Macromolecules .............. 177
6.8. Macromolecules Applied to Pharmaceutical Chemistry ..................178
6.9. Macromolecular Technologies: Applications and Improvements .....180
6.10. Experiences with Applications of Macromolecular
Tools in Supramolecular Crystallography ...................................... 182
6.11. Applications of Surface-Grafted Macromolecules ..........................183
6.12. Industrial Applications of Macromolecules ...................................185
6.13. Antioxidative Biomacromolecules ................................................. 186
6.14. Applications of Antioxidative Biomacromolecules ........................ 190
6.15. Conclusion ................................................................................... 194
References ............................................................................................. 195
Introduction to the Study of Macromolecules
170
Polymers now are found in almost every aspect of our daily lives. Ever since
the introduction of the first entirely synthetic plastic by Leo Baekeland in
1907, this field of study has expanded dramatically. New polymers were
developed, and their properties were constantly enhanced.
Simultaneously, polymerization methods were created and improved
in order to obtain control over, for example, the average molecular weight
(Mn), dispersity (Đ), architecture, or usefulness of the produced polymers.
However, the twenty-first century has brought new problems and new fields
of research, such as sequence-controlled polymers.
6.1. INTRODUCTION
This phrase refers to polymers in which the monomer sequence is managed
and the dispersity is decreased. However, control over the sequencing or
the length of the polymer is not always total, and the characteristics of the
resulting polymer might be influenced by the intrinsic molecular weight
distribution.
Polymer chemists are now striving for more precise chemical methods
in order to produce synthetic uniform macromolecules with unique features,
inspired by sophisticated technologies found in nature, particularly the
functioning of biomacromolecules such as DNA or proteins. As a result, a
new discipline known as “sequence-defined polymers” has eme ged.
The intense pursuit of ultraprecise, discrete (i.e., strictly monodisperse)
synthetic macromolecules resulted in the invention of novel synthetic
techniques or the reuse/adaption of previously recognized chemical
instruments for their synthesis. Solid phase synthesis is one of the most
extensively used processes.
Although this technology was originally designed for peptide synthesis,
it has now been widely used to generate distinct synthetic oligomers. As a
result, numerous chemical processes that were previously done in solution
have been adapted to solid phase synthesis such as copper-catalyzed azidealkyne cycloadditions, Passerini three-component reactions, and thiolactone
chemistry.
The simplicity of purifying drives the interest in solid phase synthesis,
but it has certain downsides as well. For example, chain length can be limited
due to incomplete coupling stages or oligomer aggregation, restricting the
accessibility of chain ends, and so on. As a result, several research groups
choose solution phase synthesis techniques. The reaction can be carried out
Functional Applications of Macromolecules
171
with the aid of soluble polymer support or directly in solution. Furthermore,
several approaches in the solution have the advantage of being up-scalable.
6.2. CHAIN LENGTH LIMITATION AND UPSCALABILITY ASPECTS OF DISCRETE
SYNTHETIC MACROMOLECULES
The fields where discrete synthetic macromolecules are used in recent
years, although it should be noted that each specific application has various
requirements in terms of scalability and chain length of the individual
macromolecules.
This means that while developing a unique synthetic method to produce
tailor-made homogenous macromolecules, the nature of the desired
application should always be examined. Certain applications demand a huge
volume of product and/or lengthy macromolecular chains, whilst others
require merely milligrams of oligomeric structures.
As a result, a quick review of several procedures that have the potential
to be scaled-up or result in lengthy polymer chains is provided, while the
reader is directed elsewhere for a detailed overview of the various synthetic
processes. A popular strategy focuses on the iterative coupling of building
pieces and can be accomplished directly in solution or with the help of a
(soluble) solid support.
While the latter has many advantages for the development of specific
macromolecules (for example, purification is limited to filtration, an excess
of reagents can be used to increase conversion as well as reaction kinetics,
and possible automation), milligram scale reactions in a research lab
environment limit the applications to specific areas of research.
Despite their modest number, certain research investigations have shown
that larger scales or longer macromolecules may be achieved efficientl
using support-based methodologies.
Fuzeon, a peptide composed of amino acids, is manufactured on a multiton scale each year utilizing a combination of solid- and solution-phase
techniques. Despite having a biological backbone, this macromolecule
indicates that scaling concerns can be addressed in theory. Iterative
procedures in solution, on the other hand, have less restrictions on the
reaction scale but frequently need the use of labor-intensive purification
processes such as column chromatography.
Introduction to the Study of Macromolecules
172
Figure 6.1. Basic molecules of life.
Source : Image by Wikimedia commons
Surprisingly, Meier and colleagues discovered that increasing the chain
length facilitated the purification of distinct synthetic macromolecules
using column chromatography for their specific technique. This seemingly
contradictory discovery comes from the fact that an overabundance of low
molecular weight chemicals may be easily eluted using a polar solvent,
followed by the collection of the desired oligomer.
Gao and colleagues employed a polar-inversed technique to preferentially
precipitate their uniform, positively charged macromolecules in the presence
of unreacted neutral monomers, avoiding lengthy work-up processes. In
another paper, Livingston and colleagues coupled a liquid phase method
with selective molecular sieving to create homogeneous poly-ethers using
simple sieving and extraction stages.
Porel and Alabi showed that a careful choice of building blocks might
restrict the purifying procedure to a simple aqueous extraction. This method
resulted in the multigram synthesis of monodisperse macromolecules, which
were then utilized to create polymer networks through thiolene chemistry.
To the best of the available knowledge, the latter paper is the first to use
sequence-defined oligomers in a bulk material
Functional Applications of Macromolecules
173
6.3. APPLICATIONS OF DISCRETE SYNTHETIC MACROMOLECULES IN MATERIAL SCIENCE
6.3.1. Macromolecular Data Storage
This has lately been said that the supply of microchip-grade silicon will not
be able to keep up with the rising demand for storing all of the data that is
produced every day, thus researchers are looking into alternatives to present
data storage medium.
It is scarcely surprising that DNA is one of the alternatives, as nature
has improved the process of storing a full genome in these biopolymers over
the previous billion years, and DNA sequencing has been a topic of study
for decades.
However, when employing sequence-defined synthetic macromolecules
to encode information, some of the inherent limitations associated with DNA
(e.g., hydrolysis of phosphodiester bonds, low Shannon capacity, costly
and limited number of building blocks) may be addressed when employing
sequence-defined synthetic macromolecules to encode information at the
molecular level.
Furthermore, whereas DNA sequences are made up of four distinct
nucleobases, the number of possible repeating units that may be included
into sequence-definedmacromolecules is far greater, possibly permitting the
development of vastly denser data storage medium.
This may be shown as follows: Using a binary alphabet allows for the
synthesis of 64 different hexamers, whereas ten different building blocks
can already result in 106 different hexamers.
Boukis and Meier used this method to generate a “molecular alphabet”
of 116 distinct building blocks by merging two multicomponent processes.
This accomplishment eventually allowed them to store up to 24 bits of data
per repeating unit. In a subsequent paper, the same researchers devised a
synthetic technique based on the Passerini three component reactions in
which the backbone and side chain of each individual repeating unit can
be altered Due to the greater number of potential permutations, this dual
sequence definition resulted in larger storage capacity when compared to
more traditional techniques.
Similarly, Du Prez and colleagues used a similar method to encode a
QR code onto a series of short sequence-defined oligomers. In this case, the
use of fifteen different acrylates in their automated amine-thio-lactone-ene
Introduction to the Study of Macromolecules
174
protocol avoided the need for longer macromolecular chains, which can be a
difficul challenge when using a solid phase strategy to store a large amount
of information because the backbone and side chain of each individual
repeating unit could be varied.
6.4. SELF-ASSEMBLY OF DISCRETE SYNTHETIC MACROMOLECULES
6.4.1. Self-Assembly of Discrete Block Copolymers
Nature is full of interactions between molecules that result in higher-ordered
structures. The assembly of phospholipids to create the cellular membrane
or the construction of multiple copies of coat proteins in the outer shell
of viruses, which gives them their characteristic forms, are two common
examples.
The molecular assembly of tiny amphiphilic compounds has been
intensively researched, and theoretical models based on molecular geometry
and supramolecular interactions have been devised to interpret and predict
their behavior. Block copolymers may also have a proclivity to assemble
into well-defined morphologies
This phenomenon is caused by incompatibility between the distinct
blocks, which segregate to minimize interfacial energy. Similarly, theoretical
and computational models have been established to describe this.
Figure 6.2. Plasmonic optical fiber for bacteria manipulation
Source: Image by opg.optica.org
Functional Applications of Macromolecules
175
However, these models frequently presume discrete block copolymers,
in contrast to the scattered nature of the real polymers employed in
experimental research, which are generated using various live and controlled
polymerization processes.
As a result, these models do not capture the entire image and do not
account for variations in the chain length. Nonetheless, the continual
growth of the area of sequence-controlled polymers has already permitted
the production of discrete equivalents to conventional scattered commercial
polymers.
Recent studies by the Meijer and Hawker groups have shown that
even extremely modest dispersity can have a substantial effect on the selfassembly capabilities of block copolymers in the low molecular weight
domain.
6.5. FOLDAMERS BASED ON UNIFORM MACROMOLECULES
The folding of biomacromolecules into secondary, tertiary, or even quaternary
structures allows them to execute a wide range of sophisticated yet amazing
activities like molecular recognition, transportation, information storage,
and catalysis while utilizing a restricted repertory of building blocks (i.e.,
20 amino acids and 4 nucleobases).
Furthermore, the folding of macromolecules into native states is a rather
complex process that involves a variety of consequences.
On the one hand, favorable enthalpic interactions including intramolecular
hydrogen bonding, electrostatic-, hydrophobic-, and van der Waals contacts
encourage folding.
Building a secondary structure, additionally, is connected to restricting
the level of freedom and is hence undesirable in terms of entropy. Therefore,
folding could be viewed as a balance between antagonistic interactions,
despite being a very cooperative process for most circumstances.
Most research has shown that the fundamental principles guiding
the folding of proteins may be generalized to their synthetic equivalents
throughout time. Indeed, other research groups began to investigate if
uniform macromolecules based on abiotic building blocks were also capable
of adopting special 3D structures that may enhance the distinctive qualities
of biomacromolecules.
Introduction to the Study of Macromolecules
176
6.6. APPLICATIONS OF DISCRETE SYNTHETIC MACROMOLECULES IN LIFE SCIENCE
Nature uses controlled amino acid sequences to generate higher order
structures such as -helices or -sheets that form peptides or proteins. Because
the features of these biopolymers are entirely dependent on the correct
sequence of building blocks, a focus on sequence control has proved harmful
in biologically important applications.
Regardless of the fact that current research is mostly focused on the
usage of narrow dispersity polymers derived from physiologically relevant
monomers, examples from recent literature demonstrate many applications
of discrete macromolecules in life sciences.
6.6.1. Antibacterial Properties of Discrete Synthetic Macromolecules
Though medicines have significantly enhanced life span throughout the last
century, the emergence of antibiotic-resistant bacteria is among the most
serious threats to human health. As a result, researchers have been seeking
alternatives to standard antibiotics.
Antimicrobial peptides, which are expressed by the immune systems of
all multicellular animals, have motivated their efforts. All of those are short
peptides, with 88 percent of the 3180 known structures including fewer
than 50 amino acids. While these peptides have a wide range of structural
characteristics, many of them have comparable physicochemical features.
They have a net positive charge due to cationic amino acids (e.g., lysine
or arginine), but they also have a substantial proportion of hydrophobic
amino acid residues, which are essential for their action.
Due to their positive ions, they may stick and deposit semi-selectively
on a bacterial cell membrane, which is richer in negatively charged
phospholipids than mammalian cells.
Therefore, the insertion of hydrophobic moieties has the ability to rupture
the membrane, destroying the bacterial cells. The use of antimicrobial
peptides as antibiotics is hampered by their high manufacturing costs and
susceptibility to proteolysis. As a result, synthetic mimics that mirror these
critical physicochemical features have been produced.