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Green chemistry places an emphasis on safer chemicals, waste reduction, and efficiency. Processes should be optimized with green chemistry at the forefront of decision making, embedded into research at the earliest stage. To assist in this endeavor, we present a spreadsheet that can be used to interpret reaction kinetics via Variable Time Normalization Analysis (VTNA), understand solvent effects with linear solvation energy relationships (LSER), and calculate solvent greenness. With this information, new reaction conditions can be explored in silico, calculating product conversions and green chemistry metrics prior to experiments. The application of this tool was validated with literature case studies. Reaction performance was predicted and then confirmed experimentally for examples of aza-Michael addition, Michael addition, and an amidation. The combined analytical package presented herein permits a thorough examination of chemical reactions, so that the variables that control reaction chemistry can be understood, optimized, and made greener for research and education purposes.

There is demand for safer and bio-based solvents, brought on by legislation and sustainability objectives. The prediction of physical properties is highly desirable to help design new molecules. Here we present an in silico approach to obtain calculated Kamlet-Abboud-Taft solvatochromic parameters using virtual experiments. The tautomerisation equilibrium of methyl acetoacetate and dimedone was calculated in different solvents with COSMO-RS theory and converted into estimates of solvent dipolarity and hydrogen bond accepting ability, respectively. Hydrogen bond donating ability was calculated as a function of the electron deficient surface area on protic solvents. These polarity descriptors correlate with rate constants and equilibria, and so ability of calculated Kamlet-Abboud-Taft solvatochromic parameters to recreate experimental free energy relationships was tested with sixteen case studies taken from the literature. The accuracy of the calculated parameters was also satisfactory for solvent selection, as demonstrated with a 1,4-addition reaction and a multicomponent heterocycle synthesis.

Substrate mechanics (e.g., stiffness and topography of the microenvironment) are likely critical for driving normal morphogenesis and tissue development. As such, substrate mechanics imposed by hydrogels have been exploited to guide the lineage differentiation of stem cells and to drive stemness. In this work, we chemically modified gelatin hydrogels through glyceraldehyde cross-linking to render them suitable for cell culture. The modified hydrogels proved to be ideal for embryonic stem cell osteogenesis, initially providing a soft nonadhesive surface for the formation of embryoid bodies. They subsequently degraded in culture to afford a harder surface during osteoblast differentiation. The gels synthesized are highly fluorescent, relatively easy to prepare, and can potentially aid in overcoming the challenge of imaging changes to the microenvironments of cells during three-dimensional cell culture. Exploiting these materials could lead to the development of tissue-engineered products of increased complexity and rational treatment strategies.

We compared the effects of zero-length cross-linkers 1-ethyl-3 (3dimethylaminopropyl) carbodiimide (EDC) and non-zero-length cross-linkers glycolaldehyde and glyceraldehyde on the optical and structural properties of three-dimensional (3D) collagen hydrogels. We evaluated these effects by multiphoton microscopy (MPM) that combined two-photon fluorescence (TPF) and second harmonic generation (SHG) contrasts and transmission electron microscopy (TEM). The collagen hydrogels were incubated separately with the above-mentioned reagents present at the concentration of 0.1 M. The incubation with glycolaldehyde and glyceraldehyde induced strong autofluorescence within the gels. We followed the formation of fluorescence with TPF signals in situ and in real time as well as characterized the micro- and nanostructures within cross-linked hydrogels by examining SHG and TEM images respectively. As detected in the SHG images, glycolaldehyde- and glyceraldehyde-modified 5-10 μm "fiberlike" collagen structures to longer, 20 μm and more, aggregated strands while EDC had minimal effect on the microstructure. TEM revealed that glycolaldehyde and glyceraldehyde either completely eliminated collagen's characteristic native fibrillar striations or generated uncharacteristic fibrils with extensions. EDC preserved the native striation patterns, decreased the fibril diameters and effectively homogenized the fibrils within hydrogels assembled at 1.8-4.68 g/L collagen concentrations and 37 °C. Our findings provide a clear understanding on how different cross-linking reagents have very different effects on the collagen hydrogels. This understanding is critical for advancing tissue engineering and wound healing applications., (© 2011 American Chemical Society)

The cross-linking with reducing sugars, known as glycation, is used to increase stiffness and strength of tissues and artificial collagen-based scaffolds. Nondestructive characterization methods that report on the structures within these materials could clarify the effects of glycation. For doing this nondestructive evaluation, we employed an in situ one-photon fluorescence as well as multiphoton microscopy method that combined two-photon fluorescence and second harmonic generation signals. We incubated collagen hydrogels with glyceraldehyde, ribose, and glucose and observed an increase in the in situ fluorescence and structural alterations within the materials during the course of glycation. The two-photon fluorescence emission maximum was observed at about 460 nm. The fluorescence emission in the one-photon excitation experiment (λ(ex) = 360 nm) was broad with peaks centered at 445 and 460 nm. The 460 nm emission component subsequently became dominant during the course of glycation with glyceraldehyde. For the ribose, in addition to the 460 nm peak, the 445 nm component persisted. The glucose glycated hydrogels exhibited broad fluorescence that did not increase significantly even after 6 weeks. As determined from measuring the fluorescence intensity at the 460 nm maximum, glycation with glyceraldehyde was faster compared to ribose and generated stronger fluorescence signals. Upon excitation of glycated samples with 330 nm light, different emission peaks were observed.