Research Topics（Published topics only）

1. Successive conversion of plant biomass to ethanol by using zwitterionic liquids

Plant biomass such as grass, trees, used paper, and disposable chopsticks is known as the most abundant biomass in the world. The main components of the plant biomass are composed of polysaccharides such as cellulose and hemicellulose and aromatic polymers such as lignin. We researches efficient biorefinery with ionic liquids: polysaccharides are dissolved and separated and then converted to bioethanol using enzymes and microorganisms.

All biomass solvents, including ionic liquids, are highly toxic. Therefore, after the biomass was dissolved and hydrolyzed, it could not be continuously fermented by microorganisms. We have developed a "carboxylate-type zwitterionic liquid" which has high biocompatibility. The biocompatible zwitterionic liquid enabled one-pot ethanol production—continuous dissolution, hydrolysis, and fermentation in one reaction pot. It leads to significant energy-saving.

Published papers

1. K. Kuroda*, H. Satria, K. Miyamura, Y. Tusge, K. Ninomiya, K. Takahashi
Design of Wall-Destructive but Membrane-Compatible Solvents

J. Am. Chem. Soc., 139, 16052-16055 (2017)
Supplementary Cover

2. H. Satria, K. Kuroda*, Y. Tsuge, K. Ninomiya, K. Takahashi
Dimethyl sulfoxide enhances both cellulose dissolution ability and biocompatibility of a carboxylate-type liquid zwitterion

New. J. Chem., 42, 13225-13228 (2018)
Front Cover

3. G. Sharma, K. Takahashi, K. Kuroda*
Polar Zwitterion/Saccharide-Based Deep Eutectic Solvents for Cellulose Dissolution

Carbohydr. Polym., 267, 118171 (2021)

4. T. Komori, H. Satria, K. Miyamura, A. Ito, M. Kamiya, A. Sumino, T. Onishi, K. Ninomiya, K. Takahashi, J. L. Anderson, T. Uto*, K. Kuroda*
Essential requirements of biocompatible cellulose solvents

ACS Sustain. Chem. Eng., 9, 11825-11836 (2021)

5. R. Kadokawa, T. Endo, Y. Yasaka, K. Ninomiya, K. Takahashi, K. Kuroda*
Cellulose preferentially dissolved over xylan in ionic liquids through precise anion interaction regulated by bulky cations

ACS Sustain. Chem. Eng., 9, 8686-8691 (2021)
Supplementary Cover

6. F. Jesusa, H. Passos, A. M. Ferreira, K. Kuroda, J. L. Pereira, F. Gonçalves, J. A. P. Coutinho, S. P.M. Ventura*
Zwitterionic compounds are less ecotoxic than their analogous ionic liquid

Green Chem., 23, 3683-3692 (2021)

2. Zwitterionic liquids as novel non-aqueous solvents in life sciences

Dozens of percent of cells and living organisms are composed of water, and thus water is basically used as a solvent in life sciences. On the other hand, organic solvents are used when cells are cryopreserved or when water-insoluble drugs or dyes are dissolved. Dimethyl sulfoxide (DMSO) is known to have low toxicity among organic solvents, but in recent years it has been reported that its toxicity cannot be ignored. On the other hand, DMSO has a long research history and it has been thought that there is no alternative solvent.

On the other hand, We thought that the low-toxicity zwitterionic liquids we reported could solve the issue of DMSO toxicity. The toxicity of the zwitterionic liquids was lower than that of DMSO, and it did not affect zebrafish embryos unlike DMSO. DMSO is also known to affect cell functions (e.g., cell cycle and iPS cell differentiation), but the zwitterionic liquids did not. These results suggest that the zwitterionic liquids can be novel non-aqueous solvents that exceed DMSO.

2-1. Zwitterionic liquids as cryoprotectants

There is an increasing demand for technology for cryopreserving and long-term storage of cells, such as sperm banks. In order to cryopreserve cells, addition of a cryoprotectants such as DMSO is necessary. However, there are many cells that cannot be efficiently cryopreserved by conventional cryoprotectants, and the development of new cryoprotectants is highly demanded. We thought that zwitterionic liquids could be candidates. Human fibroblasts could be well cryopreserved using a 5 wt% zwitterionic liquid aqueous solution. The cryopreservation efficiency was equivalent to that of a commercially available cryoprotectant. The solution contains zwitterionic liquid and water; indicating that the zwittterionic liquid-type cryoprotectants are expected to enable cryopreservation of cells that have been difficult to cryopreserve, through optimization.

Published papers

1. K. Kuroda*, T. Komori, K. Ishibashi, T. Uto, I. Kobayashi, R. Kadokawa, Y. Kato, K. Ninomiya, K. Takahashi, E. Hirata*
Non-aqueous, zwitterionic solvent as an alternative for dimethyl sulfoxide in the life sciences

Commun. Chem., 3, 163 (2020)
Open Access

2. Y. Kato, T. Uto, D. Tanaka, K. Ishibashi, A. Kobayashi, M. Hazawa, R. W. Wong, K. Ninomiya, K. Takahashi, E. Hirata*, K. Kuroda*
Synthetic zwitterions as efficient non-permeable cryoprotectants

Commun. Chem., in press (2021)
Open Access

2-2. Zwitterionic liquids as solvents for poorly water-soluble drugs

There are many poorly water-soluble drugs and dyes, and they are dissolved once in DMSO and then added to the media in most cases. Oil or ethanol are also used when administered to the human or mice. However, side effects caused by DMSO and ethanol are also known, and solvents that replace them are required. Zwitterionic liquids can be the next generation solvents to take that role. For example, the zwitterionic liquid (or its aqueous solutions) dissolved cisplatin, a poorly water-soluble anticancer drug.

Furthermore, there are many drugs that do not dissolve even in DMSO or ethanol at all, and therefore evaluation of their efficacy has been impossible. The zwitterionic liquids are also expected to dissolve such insoluble drugs.

Pictures after adding poorly water-soluble cisplatin in (left) water and (right) a zwitterionic liquid aqueous solution.

Published papers

Commun. Chem. 3, 163 (2020)
Open Access

2. R. Kadokawa, T. Fujie, G. Sharma, K. Ishibashi, K. Ninomiya, K. Takahashi, E. Hirata*, K. Kuroda*
High loading of trimethylglycine promotes aqueous solubility of poorly water-soluble cisplatin

Sci. Rep., 11, 9770 (2021)
Open Access

3. Development of low-cost and quick synthsis of zwitterionic liquids

The zwitterionic liquid we typically employ is very expensive and its synthesis is somewhat complicated. We shifted the reagents and synthetic route and constructed the low-cost and time-saving synthetic procedure.

Published papers

1. G. Sharma, Y. Kato, A. Hachisu, K. Ishibashi, K. Ninomiya, K. Takahashi, E. Hirata, Kosuke Kuroda*
Synthesis of a cellulose dissolving liquid zwitterion from general and low-cost reagents

Cellulose, 29, 3017-3024 (2022)

2. T. Komori, Y. Kato, K. Ishibashi, K. Ninomiya, N. Wada, D. Hirose, K. Takahashi, E. Hirata, K. Kuroda*
Characterization and Application of Carboxylate-type zwitterions synthesized by one-step

J. Ion. Liq., 2, 100027 (2022)

Previous topics

Direct preparation of “Kampo” gels from herbal medicinal plants

Published papers

1. C. Kodo, K. Kuroda*, K. Miyazaki, H. Ueda, K. Ninomiya, K. Takahashi
Direct preparation of gels from herbal medicinal plants by using a low toxicity liquid zwitterion

Polym. J., 467-472 (2020)

Flame-retardant thermoplastics derived from plants

Published papers

1. R. Nishita, K. Kuroda*, S. Ota, T. Endo, S. Suzuki, K. Ninomiya, K. Takahashi
Flame-retardant thermoplastics derived from plant cell wall polymers by single ionic liquid substitution

New. J. Chem., 43, 2057-2064 (2019)

2. R. Nishita, K. Kuroda*, S. Suzuki, K. Ninomiya, K. Takahashi
Flame-retardant plant thermoplastics directly prepared by single ionic liquid substitution

Polym. J., 51, 781–789 (2019)

Switchable ionic liquids from/to zwitterions

Published papers

1. K. Kuroda*, Y. Shimada, K. Takahashi
CO₂-triggered fine tune of electrical conductivity via tug-of-war between ions

New J. Chem., 42, 15528-15532 (2018)
Front Cover

2. K. Kuroda*, Y. Shimada, K. Takahashi
Hand-holding and releasing between the anion and cation to change their macroscopic behavior in water

Green Energy Envrion., 4, 127-130 (2019)

Lignin-derived compatibilizing agents for carbon fiber reinforced plastics

Published papers

1. H. Sakai, K. Kuroda*(co-first author), S. Muroyama, T. Tsukegi, R. Kakuchi, K. Takada, A. Hata, R. Kojima, T. Ogoshi, M. Omichi, K. Ninomiya, K. Takahashi
Alkylated alkali lignin for compatibilizing agents of carbon fiber reinforced plastics with polypropylene

Polym. J., 50, 281-284 (2018)

2. H. Sakai, K. Kuroda*(co-first author), T. Tsukegi, T. Ogoshi, K. Ninomiya, K. Takahashi*
Butylated lignin as a compatibilizing agent for polypropylene–based carbon fiber-reinforced plastics

Polym. J., 50, 997-1002, (2018)

Hydrolysis of cellulose by acidic ionic liquids

Published papers

1. K. Kuroda*, K. Miyamura, H. Satria, K. Takada, K. Ninomiya, K. Takahashi*
Hydrolysis of cellulose using an acidic and hydrophobic ionic liquid, and subsequent separation of glucose aqueous solution from the ionic liquid and 5-(hydroxymethyl)furfural

ACS Sustain. Chem. Eng., 4, 3352-3356 (2016)

2. K. Kuroda, K. Inoue, K. Miyamura, K. Takada, K. Ninomiya, K. Takahashi*
Enhanced Hydrolysis of Lignocellulosic Biomass Assisted by a Combination of Acidic Ionic Liquids and Microwave Heating

J. Chem. Eng. Jpn., 49, 809-813 (2016)

3. H. Satria, K. Kuroda*(co-first author), T. Endo, K. Takada, K. Ninomiya, K. Takahashi*
Efficient hydrolysis of polysaccharides in bagasse by in situ synthesis of an acidic ionic liquid after pretreatment

ACS Sustain. Chem. Eng., 5, 708-713 (2017)

4. K. Kuroda*, K. Inoue, K. Miyamura, K. Takada, K. Ninomiya, K. Takahashi*
Efficient Hydrolysis of Lignocellulose by Acidic Ionic Liquids under Low-Toxic Condition to Microorganisms

Catalysts, 7, 108 (2017)
Open Access