Salt Effects on the Phase Behavior and Cocrystallization Kinetics of POCB-Water Mixtures.

Mixtures of water with polyoxacyclobutane (POCB) have a unique phase diagram which combines liquid-liquid equilibrium (LLE) at high temperatures and cocrystallization of a POCB-hydrate at low temperatures. Such cocrystal hydrate formation is extremely rare among polymers. We report on the effects of adding NaCl salt on the phase behavior of POCB-water mixtures and the kinetics of hydrate crystallization from such mixtures. Salt loadings of less than 0.1 wt % were found to greatly expand the LLE region. Salt loadings of ∼10 wt % were found to significantly decrease the melting temperature of the hydrate below its ∼37 °C value under salt-free conditions. The hydrate was found to be remarkably tolerant of salt and persists at room temperature even when equilibrated with salt-saturated water. Salt was found to slow down hydrate crystallization, and the degree of slowing was greater than that expected from the salt-induced decrease in undercooling due to melting point depression.

Comparing the Effectiveness of 2 Cardiac Rehabilitation Exercise Therapy Programs.

Cardiovascular diseases are among the leading causes of morbidity and mortality in Canada, highlighting the critical role of disease prevention and risk reduction programs. Cardiac rehabilitation (CR) is a key component of comprehensive cardiovascular care. Currently, more than 200 CR programs are established across the country, varying in duration, number of in-person supervised exercise sessions, and recommendations for exercise frequency at-home. In an increasingly cost-conscious healthcare environment, the effectiveness of healthcare services must be consistently reevaluated. This study evaluates the impact of 2 CR programs implemented by the Northern Alberta Cardiac Rehabilitation Program, by comparing peak metabolic equivalents achieved by study participants in each program. We hypothesize that our "hybrid" CR program, which is structured as an 8-week program with weekly in-person exercise sessions and a prescribed home exercise program, has patient outcomes similar to those of our "traditional" CR program, which required biweekly in-person exercise sessions over the course of 5 weeks. The results of this study may have implications for evaluating how to minimize barriers to both rehabilitation participation and long-term effectiveness of CR programs. The results may help inform the structuring and funding of future rehabilitation programs.

Les maladies cardiovasculaires (MCV) sont parmi les premières causes de morbidité et de mortalité au Canada d'où l'importance des programmes de prévention des MCV et de réduction du risque cardiovasculaire. La réadaptation cardiaque est un élément clé du continuum de soins cardiovasculaires. À l'heure actuelle, il existe plus de 200 programmes de réadaptation cardiaque au pays, qui diffèrent tant par leur durée, par le nombre de séances d'exercice supervisées en personne que par leurs recommandations sur la fréquence des exercices à domicile. Dans un contexte où le coût des soins de santé est de plus en plus préoccupant, l'efficience des services de santé doit constamment être réévaluée. Cette étude évalue les effets de deux programmes de réadaptation cardiaque instaurés par le Cardiac Rehabilitation Program du nord de l'Alberta en comparant l'équivalent métabolique maximal obtenu par les participants à l'étude pour chaque programme. L'hypothèse de départ était que notre programme de réadaptation cardiaque « hybride ¼, qui consiste d'une part en un programme de huit semaines de séances hebdomadaires d'exercices en personne et d'autre part en un programme d'exercices à domicile, donnerait des résultats semblables à ceux de notre programme « traditionnel ¼ de réadaptation cardiaque. Celui-ci se compose de deux séances d'exercices en personne par semaine, pendant cinq semaines. Les résultats de cette étude pourraient nous aider à réduire les obstacles qui nuisent à la participation aux programmes de réadaptation et à l'efficience à long terme de ces programmes. Nous espérons apporter un éclairage sur la structure et le financement des futurs programmes de réadaptation.

Participant Exercise-Session Attendance in Community-Based, Bridging, and Hospital-Based Cardiac Rehabilitation: A Retrospective Case-Control Study.

Background: A paucity of studies have investigated participant attendance in community-based and hybrid cardiac rehabilitation programs in the Canadian setting. We compared exercise-session attendance of community-based, bridging (hospital plus community-based), and hospital-based participants who attended a high-volume cardiac rehabilitation program in Alberta, Canada. Methods: Exercise sessions attended and participant characteristics were collected and analyzed from 230 records of patients who attended cardiac rehabilitation between 2016 and 2019. Community-based (n = 74) and bridging (n = 41) program participants were age- and sex-matched in a 1:1 ratio to hospital-based participants. The number of exercise sessions attended was compared among program groups, between female and male patients, and for patients with vs without cardiac surgery. The percentage of exercise sessions attended was also compared among program groups. Results: Bridging participants attended the greatest number of exercise sessions (median = 10.0 sessions) and demonstrated a significantly higher percentage of sessions attended (91%, 25th and 75th percentile interquartile range [IQR] = 64, 100%) than matched hospital participants (median = 6.0 sessions; 63%, 25, 75 IQR = 13, 94%; P = 0.01). Percentage of sessions attended did not differ for bridging and community-based participants (P = 0.30). Exercise-session attendance was similar for community-based participants (median = 6.0 sessions; 75%, 25, 75 IQR = 38%, 88%) vs their hospital matches (median = 6.0 sessions; 81%, 25, 75 IQR = 38%, 100%; P ≥ 0.37), as well as for female vs male patients (median = 7.0 sessions for both sexes; P = 0.66), and for surgical vs nonsurgical patients (median = 7.0 sessions; P = 0.48). Female patients in the bridging program attended significantly more exercise sessions in the community, compared with male patients in the bridging program (P = 0.02). Conclusions: Bridging participants attended the most exercise sessions overall and demonstrated a higher percentage attendance than hospital-based participants. These results suggest that a hybrid program consisting of hospital and community-based exercise was favourable for exercise-session attendance. Given modern approaches to de-medicalize cardiac rehabilitation, our findings further support the provision of community program offerings, without detriment to patient session attendance.

Introduction: Peu d'études ont porté sur la participation des patients aux programmes communautaires ou hydrides de réadaptation cardiaque du Canada. Nous avons comparé la participation des patients aux séances d'entraînement en milieu communautaire, de transition (en milieu hospitalier et milieu communautaire) et en milieu hospitalier d'un programme de réadaptation cardiaque à volume élevé de l'Alberta, au Canada. Méthodes: Nous avons collecté et analysé les données sur les séances d'entraînement suivies et les caractéristiques des participants provenant de 230 dossiers de patients qui avaient participé à la réadaptation cardiaque entre 2016 et 2019. Les participants du programme en milieu communautaire (n = 74) et du programme de transition (n = 41) ont été appariés par âge et sexe aux participants du programme en milieu hospitalier selon un ratio 1:1. Le nombre de séances d'entraînement suivies a été comparé entre les groupes du programme, entre les patientes et les patients, et entre les patients qui avaient subi ou non une chirurgie cardiaque. Le pourcentage des séances d'entraînement suivies a aussi été comparé entre les groupes du programme. Résultats: Les participants du programme de transition ont assisté au plus grand nombre de séances d'entraînement (médiane = 10,0 séances) et ont démontré un pourcentage significativement plus élevé de séances suivies (91 %, 25e et 75e percentile [25, 75] intervalle interquartile [IIQ] = 64, 100 %) que les participants appariés du programme en milieu hospitalier (médiane = 6,0 séances; 63 %, 25, 75 IIQ = 13, 94 %; P = 0,01). Le pourcentage de séances suivies ne différait pas entre les participants du programme de transition et les participants du programme en milieu communautaire (P = 0,30). La participation aux séances d'entraînement était similaire entre les participants du programme en milieu communautaire (médiane = 6,0 séances; 75 %, 25, 75 IIQ = 38 %, 88 %) et les participants appariés du programme en milieu hospitalier (médiane = 6,0 séances; 81 %, 25, 75 IIQ = 38 %, 100 %; P ≥ 0,37), de même qu'entre les patientes et les patients (médiane = 7,0 séances pour les deux sexes; P = 0,66), et les patients opérés et les patients non opérés (médiane = 7,0 séances; P = 0,48). Les patientes du programme de transition ont participé à un nombre plus important de séances d'entraînement en milieu communautaire que les patients du programme de transition (P = 0,02). Conclusions: Les participants du programme de transition ont dans l'ensemble assisté à la plupart des séances d'entraînement et ont démontré un pourcentage plus élevé de participation que les participants du programme en milieu hospitalier. Ces résultats indiquent qu'un programme hybride qui consiste en un entraînement en milieu hospitalier et en milieu communautaire favorisait la participation aux séances d'entraînement. Compte tenu des approches contemporaines de démédicalisation de la réadaptation cardiaque, nos conclusions justifient d'autant plus la mise à disposition de programmes en milieu communautaire, et ce, sans compromettre la participation des patients aux séances.

Chirality-Directed Regioselectivity: An Approach for the Synthesis of Alternating Poly(Lactic-co-Glycolic Acid).

We report the synthesis of alternating poly(lactic-co-glycolic acid) via a regioselective ring-opening polymerization of (S)-methyl glycolide. An enantiopure aluminum salen catalyst with binaphthyl backbone facilitates the regioselective ring-opening of this unsymmetrical cyclic diester exclusively at the glycolide acyl-oxygen bond site. This living, chain-growth polymerization is able to reach low dispersities with tailored molecular weights. Quantitative regioselectivity calculations and sequence error analysis have been established for this sequence-controlled polymer.

Learning from Peptides to Access Functional Precision Polymer Sequences.

Functional precision polymers based on monodisperse oligo(N-substituted acrylamide)s and oligo(2-substituted-α-hydroxy acid)s have been synthesized. The discrete sequences originate from a direct translation of side-chain functionality sequences of a peptide with well-studied properties. The peptide was previously selected to solubilize the photosensitizer meta-tetra(hydroxyphenyl)chlorin. The resulting peptidomimetic formulation additives preserve the drug solubilization and release characteristics of the parent peptide. In some cases, superior properties are obtained, reaching up to 40 % higher payloads and 27-times faster initial drug release.

Sequence-Controlled Polymers Through Entropy-Driven Ring-Opening Metathesis Polymerization: Theory, Molecular Weight Control, and Monomer Design.

The bulk properties of a copolymer are directly affected by monomer sequence, yet efficient, scalable, and controllable syntheses of sequenced copolymers remain a defining challenge in polymer science. We have previously demonstrated, using polymers prepared by a step-growth synthesis, that hydrolytic degradation of poly(lactic- co-glycolic acid)s is dramatically affected by sequence. While much was learned, the step-growth mechanism gave no molecular weight control, unpredictable yields, and meager scalability. Herein, we describe the synthesis of closely related sequenced polyesters prepared by entropy-driven ring-opening metathesis polymerization (ED-ROMP) of strainless macromonomers with imbedded monomer sequences of lactic, glycolic, 6-hydroxy hexanoic, and syringic acids. The incorporation of ethylene glycol and metathesis linkers facilitated synthesis and provided the olefin functionality needed for ED-ROMP. Ring-closing to prepare the cyclic macromonomers was demonstrated using both ring-closing metathesis and macrolactonization reactions. Polymerization produced macromolecules with controlled molecular weights on a multigram scale. To further enhance molecular weight control, the macromonomers were prepared with cis-olefins in the metathesis-active segment. Under these selectivity-enhanced (SEED-ROMP) conditions, first-order kinetics and narrow dispersities were observed and the effect of catalyst initiation rate on the polymerization was investigated. Enhanced living character was further demonstrated through the preparation of block copolymers. Computational analysis suggested that the enhanced polymerization kinetics were due to the cis-macrocyclic olefin being less flexible and having a larger population of metathesis-reactive conformers. Although used for polyesters in this investigation, SEED-ROMP represents a general method for incorporation of sequenced segments into molecular weight-controlled polymers.

Carnivore conservation needs evidence-based livestock protection.

Carnivore predation on livestock often leads people to retaliate. Persecution by humans has contributed strongly to global endangerment of carnivores. Preventing livestock losses would help to achieve three goals common to many human societies: preserve nature, protect animal welfare, and safeguard human livelihoods. Between 2016 and 2018, four independent reviews evaluated >40 years of research on lethal and nonlethal interventions for reducing predation on livestock. From 114 studies, we find a striking conclusion: scarce quantitative comparisons of interventions and scarce comparisons against experimental controls preclude strong inference about the effectiveness of methods. For wise investment of public resources in protecting livestock and carnivores, evidence of effectiveness should be a prerequisite to policy making or large-scale funding of any method or, at a minimum, should be measured during implementation. An appropriate evidence base is needed, and we recommend a coalition of scientists and managers be formed to establish and encourage use of consistent standards in future experimental evaluations.

Monomer sequence in PLGA microparticles: Effects on acidic microclimates and in vivo inflammatory response.

Controlling the backbone architecture of poly(lactic-co-glycolic acid)s (PLGAs) is demonstrated to have a strong influence on the production and release of acidic degradation by-products in microparticle matrices. Previous efforts for controlling the internal and external accumulation of acidity for PLGA microparticles have focused on the addition of excipients including neutralization and anti-inflammatory agents. In this report, we utilize a sequence-control strategy to tailor the microstructure of PLGA. The internal acidic microclimate distributions within sequence-defined and random PLGA microparticles were monitored in vitro using a non-invasive ratiometric two-photon microscopy (TPM) methodology. Sequence-defined PLGAs were found to have minimal changes in pH distribution and lower amounts of percolating acidic by-products. A parallel scanning electron microscopy study further linked external morphological events to internal degradation-induced structural changes. The properties of the sequenced and random copolymers characterized in vitro translated to differences in in vivo behavior. The sequence alternating copolymer, poly LG, had lower granulomatous foreign-body reactions compared to random racemic PLGA with a 50:50 ratio of lactic to glycolic acid. STATEMENT OF SIGNIFICANCE: This paper demonstrates that changing the monomer sequence in poly(lactic-co-glycolic acid)s (PLGAs) leads to dramatic differences in the rate of degradation and the internal acidic microclimate of microparticles degrading in vitro. We note that the acidic microclimates within these particles were imaged for the first time with two-photon microscopy, which gives an extremely clear and detailed picture of the degradation process. Importantly, we also document that the observed sequence-controlled in vitro processes translate into differences in the in vivo behavior of polymers which have the same L to G composition but differing microstructures. These data, placed in the context of our prior studies on swelling, erosion, and MW loss (Biomaterials2017, 117, 66 and other references cited within the manuscript), provide significant insight not only about sequence effects in PLGAs but into the underlying mechanisms of PLGA degradation in general.

Cis-Selective Metathesis to Enhance the Living Character of Ring-Opening Polymerization: An Approach to Sequenced Copolymers.

The hydrolytic behavior and physical properties of a polymer are directly related to its constituent monomer sequence, yet the scalable and controllable synthesis of sequenced copolymers remains scarcely realized. To address this need, an enhanced version of entropy-driven ring-opening metathesis polymerization (ED-ROMP) has been developed. An unprecedented level of control is obtained by exploiting the kinetic and thermodynamic differences in the metathesis activity of cis- and trans-olefins embedded in large, unstrained macrocycles. First-order rate kinetics were observed, and polymer molecular weights were found to be proportional to catalyst loading. Computational analysis suggests that incorporation of a cis-olefin into the monomer backbone both introduces a thermodynamic driving force and increases the population of metathesis-active conformers. This approach offers a generally applicable method for enhancing living character in ED-ROMP.

The impact of monomer sequence and stereochemistry on the swelling and erosion of biodegradable poly(lactic-co-glycolic acid) matrices.

Monomer sequence is demonstrated to be a primary factor in determining the hydrolytic degradation profile of poly(lactic-co-glycolic acid)s (PLGAs). Although many approaches have been used to tune the degradation of PLGAs, little effort has been expended in exploring the sequence-control strategy exploited by nature in biopolymers. Cylindrical matrices and films prepared from a series of sequenced and random PLGAs were subjected to hydrolysis in a pH 7.4 buffer at 37 °C. Swelling ranged from 107% for the random racemic PLGA with a 50:50 ratio of lactic (L) to glycolic (G) units to 6% for the sequenced alternating copolymer poly LG. Erosion followed an inverse trend with the random 50:50 PLGA showing an erosion half-life of 3-4 weeks while poly LG required ca. >10 weeks. Stereosequence was found to play a large role in determining swelling and erosion; stereopure analogs swelled less and were slower to lose mass. Molecular weight loss followed similar trends and increases in dispersity correlated with the onset of significant swelling. The relative proportion of rapidly cleavable G-G linkages relative to G-L/L-G (moderate) and L-L (slow) correlates strongly with the degree of swelling observed and the rate of erosion. The dramatic sequence-dependent variation in swelling, in the absence of a parallel hydrophilicity trend, suggest that osmotic pressure, driven by the differential accumulation of degradation products, plays an important role.

Sequence Effects in Conjugated Donor-Acceptor Trimers and Polymers.

To investigate the sequence effect on donor-acceptor conjugated oligomers and polymers, the trimeric isomers PBP and BPP, comprising dialkoxy phenylene vinylene (P), benzothiadiazole vinylene (B), and alkyl endgroups with terminal olefins, are synthesized. Sequence effects are evident in the optical/electrochemical properties and thermal properties. Absorption maxima for PBP and BPP differ by 41 nm and the electrochemical band gaps by 0.1 V. The molar emission intensity is five times greater in PBP than BPP. Both trimers are crystalline and the melting points differ by 17 °C. The PBP and BPP trimers are used as macromonomers in an acyclic diene metathesis polymerization to give PolyPBP and PolyBPP. The optical and electrochemical properties are similar to those of their trimer precursors-sequence effects are still evident. These results suggest that sequence is a tunable variable for electronic materials and that the polymerization of oligomeric sequences is a useful approach to introducing sequence into polymers.

Sequence-Controlled Copolymers Prepared via Entropy-Driven Ring-Opening Metathesis Polymerization.

A new general synthetic approach to sequenced macromolecules was developed and applied to the synthesis of polymers comprising lactic acid (L), glycolic acid (G), and ε-caprolactone (C)-derived monomer units. The new method employs entropy-driven ring-opening metathesis polymerization (ED-ROMP) to prepare copolymers with embedded sequences and controlled molecular weights. Cyclic macromonomer precursors were prepared by ring-closing metathesis of ethylene glycol (Eg)-linked sequenced oligomers bearing terminal olefins. ED-ROMP of the resulting macrocycles using Grubbs' second generation catalyst yielded poly(CL-Eg-LC-Oed), poly(CLL-Eg-LLC-Oed), poly(LGL-Eg-LGL-Oed), and poly(LGL-Eg-LGL-Hed) (Oed = octenedioc acid; Hed = hexenedioc acid). Hydrogenation produced the saturated sequenced copolymers. Molecular weight was well-controlled and could be adjusted by varying the monomer-to-catalyst ratio. Mns of 26-60 kDa were obtained (dispersities = 1.1-1.3). The methodology proved general for three different sequences and two olefinic metathesis groups.

Availability of the basal planes of graphene oxide determines whether it is antibacterial.

There are significant controversies on the antibacterial properties of graphene oxide (GO): GO was reported to be bactericidal in saline, whereas its activity in nutrient broth was controversial. To unveil the mechanisms underlying these contradictions, we performed antibacterial assays under comparable conditions. In saline, bare GO sheets were intrinsically bactericidal, yielding a bacterial survival percentage of <1% at 200 µg/mL. Supplementing saline with ≤10% Luria-Bertani (LB) broth, however, progressively deactivated its bactericidal activity depending on LB-supplementation ratio. Supplementation of 10% LB made GO completely inactive; instead, ∼100-fold bacterial growth was observed. Atomic force microscopy images showed that certain LB components were adsorbed on GO basal planes. Using bovine serum albumin and tryptophan as well-defined model adsorbates, we found that noncovalent adsorption on GO basal planes may account for the deactivation of GO's bactericidal activity. Moreover, this deactivation mechanism was shown to be extrapolatable to GO's cytotoxicity against mammalian cells. Taken together, our observations suggest that bare GO intrinsically kills both bacteria and mammalian cells and noncovalent adsorption on its basal planes may be a global deactivation mechanism for GO's cytotoxicity.

Chemical and Electrochemical Manipulation of Mechanical Properties in Stimuli-Responsive Copper-Cross-Linked Hydrogels.

Inspiration for the design of new synthetic polymers can be found in the natural world, where materials often exhibit complex properties that change depending on external stimuli. A new synthetic electroplastic elastomer hydrogel (EPEH) that undergoes changes in mechanical properties in response to both chemical and electrochemical stimuli has been prepared based on these precedents. In addition to having the capability to switch between hard and soft states, the presence of both permanent covalent and dynamic copper-based cross links also allows this stimuli-responsive material to exhibit a striking shape memory capability. The density of temporary cross links and the mechanical properties are controlled by reversible switching between the +1 and +2 oxidation states.

The effect of monomer order on the hydrolysis of biodegradable poly(lactic-co-glycolic acid) repeating sequence copolymers.

The effect of sequence on copolymer properties is rarely studied despite the precedent from Nature that monomer order can create materials of significant diversity. Poly(lactic-co-glycolic acid) (PLGA), one of the most important biodegradable copolymers, is widely used in an unsequenced, random form for both drug delivery microparticles and tissue engineering matrices. Sequenced PLGA copolymers have been synthesized and fabricated into microparticles to study how their hydrolysis rates compare to those of random copolymers. Sequenced PLGA microparticles were found to degrade at slower, and often more constant, rates than random copolymers with the same lactic to glycolic acid ratios as demonstrated by molecular weight decrease, lactic acid release, and thermal property analyses. The impact of copolymer sequence on in vitro release was studied using PLGA microparticles loaded with model agent rhodamine-B. These assays established that copolymer sequence affects the rate of release and that a more gradual burst release can be achieved using sequenced copolymers compared to a random control.

Manipulating Mechanical Properties with Electricity: Electroplastic Elastomer Hydrogels.

The dawn of the 21st century has brought with it an increasing interest in emulating the adaptive finesse of natural systems by designing materials with on-demand, tunable properties. The creation of such responsive systems could be expected, based on historical precedent, to lead to completely new engineering design paradigms. Using a bioinspired approach of coupling multiple equilibria that operate on different length scales, a material whose bulk mechanical properties can be manipulated by electrical input has been developed. The new macroscale electroplastic elastomer hydrogels can be reversibly cycled through soft and hard states while maintaining a three-dimensional shape by sequential application of oxidative and reductive potentials. This input changes the cross-linking capacity of iron ions within the gel matrix, between a poorly coordinating +2 and a more strongly binding +3 oxidation state. Inclusion of carbon nanotubes in the hydrogel preparation increases conductivity and decreases transition time.

Exploiting sequence to control the hydrolysis behavior of biodegradable PLGA copolymers.

Monomer sequence is a potentially powerful but underutilized tool for the control of copolymer properties. Sequence is demonstrated to dramatically affect the hydrolysis profile for the degradation of poly(lactic-co-glycolic acid) (PLGA), a member of the most widely used class of biodegradable polymers employed in biomedical applications. The nearly linear molecular weight loss profile and uniform thermal behavior throughout the course of the hydrolysis differ dramatically from the behavior that is exhibited by random copolymer controls with the same comonomer ratio.

Periodic incorporation of pendant hydroxyl groups in repeating sequence PLGA copolymers.

A series of repeating sequence poly(lactic-co-glycolic acid) copolymers (RSC PLGAs) has been prepared with the precise incorporation of a pendant benzyl-ether substituted monomer derived from serine. Copolymers were synthesized from the assembly of sequence-specific, stereopure dimeric, and trimeric segmers of lactic, glycolic, and (S)-3-benzyloxy-2-hydroxypropionic acids with controlled and varied tacticities. Deprotection of the hydroxyl groups was accomplished by catalytic hydrogenolysis to yield highly functionialized, hydrophilic polyesters. The (1)H and (13)C NMR spectra for all of the copolymers were consistent with sequence and stereochemical retention and lacked the signal broadening that is inherent with more random copolymers.

Iterative synthesis of heterotelechelic oligo(phenylene-vinylene)s by olefin cross-metathesis.

A novel iterative synthesis of heterotelechelic oligo(phenylene-vinylene)s using olefin cross-metathesis is reported. The metathesis homologation proceeds in good yields and allows for further functionalization, including the facile formation of donor-acceptor complexes and repeating sequence copolymers.

New insights into poly(lactic-co-glycolic acid) microstructure: using repeating sequence copolymers to decipher complex NMR and thermal behavior.

Sequence, which Nature uses to spectacular advantage, has not been fully exploited in synthetic copolymers. To investigate the effect of sequence and stereosequence on the physical properties of copolymers, a family of complex isotactic, syndiotactic, and atactic repeating sequence poly(lactic-co-glycolic acid) copolymers (RSC PLGAs) were prepared and their NMR and thermal behavior was studied. The unique suitability of polymers prepared from the bioassimilable lactic and glycolic acid monomers for biomedical applications makes them ideal candidates for this type of sequence engineering. Polymers with repeating units of LG, GLG and LLG (L = lactic, G = glycolic) with controlled and varied tacticities were synthesized by assembly of sequence-specific, stereopure dimeric, trimeric, and hexameric segmer units. Specifically labeled deuterated lactic and glycolic acid segmers were likewise prepared and polymerized. Molecular weights for the copolymers were in the range M(n) = 12-40 kDa by size exclusion chromatography in THF. Although the effects of sequence-influenced solution conformation were visible in all resonances of the (1)H and (13)C NMR spectra, the diastereotopic methylene resonances in the (1)H NMR (CDCl(3)) for the glycolic units of the copolymers proved most sensitive. An octad level of resolution, which corresponds to an astounding 31-atom distance between the most separated stereocenters, was observed in some mixed sequence polymers. Importantly, the level of sensitivity of a particular NMR resonance to small differences in sequence was found to depend on the sequence itself. Thermal properties were also correlated with sequence.